Murray Response to WMT No Action Request 2014-02-20 With Exhibits
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Transcript of Murray & Pindoria-2014
Nutrition support for bone marrow transplant patients
(Review)
Murray SM, Pindoria S
This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library
2009, Issue 1
http://www.thecochranelibrary.com
Nutrition support for bone marrow transplant patients (Review)
Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
T A B L E O F C O N T E N T S
1HEADER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2PLAIN LANGUAGE SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3OBJECTIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3METHODS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
4RESULTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
6DISCUSSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
7AUTHORS’ CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
7ACKNOWLEDGEMENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
8REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
11CHARACTERISTICS OF STUDIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
33DATA AND ANALYSES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 1.1. Comparison 1 Oral glutamine versus oral placebo studies, Outcome 1 Mean duration (+/-SD) of time in
hospital (e.g. admission to discharge or from day ’0’ to discharge).. . . . . . . . . . . . . . . . 37
Analysis 1.2. Comparison 1 Oral glutamine versus oral placebo studies, Outcome 2 Mean(+/-SD) number of days patients
had some degree of mucositis from start to end of study.. . . . . . . . . . . . . . . . . . . . 38
Analysis 1.3. Comparison 1 Oral glutamine versus oral placebo studies, Outcome 3 Number of patients who developed
line infections from start to end of study.. . . . . . . . . . . . . . . . . . . . . . . . . 39
Analysis 1.4. Comparison 1 Oral glutamine versus oral placebo studies, Outcome 4 Difference in mean % change in body
weight from start to end of the study between the trial groups.. . . . . . . . . . . . . . . . . . 40
Analysis 1.5. Comparison 1 Oral glutamine versus oral placebo studies, Outcome 5 Mean duration (+/-SD) that nutritional
intervention is given as PN.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41
Analysis 1.6. Comparison 1 Oral glutamine versus oral placebo studies, Outcome 6 Number of patients who developed >
grade 2 graft versus host disease (GVHD).. . . . . . . . . . . . . . . . . . . . . . . . . 42
Analysis 1.7. Comparison 1 Oral glutamine versus oral placebo studies, Outcome 7 Number of days(+/-SD) to achieve
normal neutrophil level (>0.5 X 10/9/l) after day 0 of BMT.. . . . . . . . . . . . . . . . . . 43
Analysis 1.8. Comparison 1 Oral glutamine versus oral placebo studies, Outcome 8 Actual numbers of patients who have
completed the study and survived to the 100th day post BMT.. . . . . . . . . . . . . . . . . . 44
Analysis 1.9. Comparison 1 Oral glutamine versus oral placebo studies, Outcome 9 Actual number of patients who have
completed the study and survived beyond day 100 post BMT.. . . . . . . . . . . . . . . . . . 45
Analysis 1.10. Comparison 1 Oral glutamine versus oral placebo studies, Outcome 10 Number with positive blood
cultures. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46
Analysis 2.1. Comparison 2 PN + glutamine versus standard PN, Outcome 1 Mean duration(+/-SD) of time in hospital
(e.g. admission to discharge or from day 0 to discharge home).. . . . . . . . . . . . . . . . . . 46
Analysis 2.2. Comparison 2 PN + glutamine versus standard PN, Outcome 2 Mean(+/-SD) cumulative mucositis score. 47
Analysis 2.3. Comparison 2 PN + glutamine versus standard PN, Outcome 3 Number of patients who developed line
infections from start to end of study.. . . . . . . . . . . . . . . . . . . . . . . . . . . 48
Analysis 2.4. Comparison 2 PN + glutamine versus standard PN, Outcome 4 Difference in mean % change in body weight
from start to end of the study between the trial groups.. . . . . . . . . . . . . . . . . . . . 49
Analysis 2.5. Comparison 2 PN + glutamine versus standard PN, Outcome 5 Mean duration (+/-SD) that nutritional
intervention is given.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50
Analysis 2.6. Comparison 2 PN + glutamine versus standard PN, Outcome 6 Number of patients who developed >/=grade
2 graft versus host disease (GVHD).. . . . . . . . . . . . . . . . . . . . . . . . . . . 51
Analysis 2.7. Comparison 2 PN + glutamine versus standard PN, Outcome 7 Number of days(+/-SD) to achieve normal
neutrophil level (>0.5 X 10/9/l) after day 0 of BMT.. . . . . . . . . . . . . . . . . . . . . 52
Analysis 2.8. Comparison 2 PN + glutamine versus standard PN, Outcome 8 Actual numbers of patients who have
completed the study and survived to the 100th day post BMT.. . . . . . . . . . . . . . . . . . 53
Analysis 2.9. Comparison 2 PN + glutamine versus standard PN, Outcome 9 Number of patients with positive blood
cultures. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 54
iNutrition support for bone marrow transplant patients (Review)
Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Analysis 3.1. Comparison 3 PN vs IV hydration, Outcome 1 Mean duration (+/-SD) of time in hospital (e.g. from discharge
admission to discharge or day 0 to discharge).. . . . . . . . . . . . . . . . . . . . . . . 55
Analysis 3.2. Comparison 3 PN vs IV hydration, Outcome 2 Mean(+/-SD) number of days patients had some degree of
mucositis from start to end of study.. . . . . . . . . . . . . . . . . . . . . . . . . . . 56
Analysis 3.3. Comparison 3 PN vs IV hydration, Outcome 3 Number of patients who developed line infections from start
to end of study.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57
Analysis 3.4. Comparison 3 PN vs IV hydration, Outcome 4 Difference in mean % change in body weight from start to
end of the study between the trial groups.. . . . . . . . . . . . . . . . . . . . . . . . . 58
Analysis 3.5. Comparison 3 PN vs IV hydration, Outcome 5 Mean duration (+/-SD) that nutritional intervention is
given.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59
Analysis 3.6. Comparison 3 PN vs IV hydration, Outcome 6 Number of patients who developed > grade 2 graft versus host
disease (GVHD).. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 60
Analysis 3.7. Comparison 3 PN vs IV hydration, Outcome 7 Number of days(+/-SD) to achieve normal neutrophil level
(>0.5 X 10/9/l) after day 0 of BMT.. . . . . . . . . . . . . . . . . . . . . . . . . . . 61
Analysis 3.8. Comparison 3 PN vs IV hydration, Outcome 8 Actual numbers of patients who have completed the study
and survived to the 100th day post BMT.. . . . . . . . . . . . . . . . . . . . . . . . . 62
Analysis 3.9. Comparison 3 PN vs IV hydration, Outcome 9 Actual number of patients who survived to day 200 post
BMT.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63
Analysis 3.10. Comparison 3 PN vs IV hydration, Outcome 10 Mean % change in albumin. . . . . . . . . . 64
Analysis 4.1. Comparison 4 PN vs enteral feeding studies, Outcome 1 Mean duration (+/-SD) of time in hospital (e.g. from
admission to discharge or day 0 to discharge).. . . . . . . . . . . . . . . . . . . . . . . 65
Analysis 4.2. Comparison 4 PN vs enteral feeding studies, Outcome 2 Mean(+/-SD) number of days patients had some
degree of mucositis from start to end of study.. . . . . . . . . . . . . . . . . . . . . . . 66
Analysis 4.3. Comparison 4 PN vs enteral feeding studies, Outcome 3 Number of patients who developed line infections
from start to end of study.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67
Analysis 4.4. Comparison 4 PN vs enteral feeding studies, Outcome 4 Difference in mean % change in body weight from
start to end of the study between the trial groups.. . . . . . . . . . . . . . . . . . . . . . 68
Analysis 4.5. Comparison 4 PN vs enteral feeding studies, Outcome 5 Mean duration (+/-SD) that nutritional intervention
is given.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69
Analysis 4.6. Comparison 4 PN vs enteral feeding studies, Outcome 6 Number of patients who developed > grade 2 graft
versus host disease (GVHD).. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 70
Analysis 4.7. Comparison 4 PN vs enteral feeding studies, Outcome 7 Number of days(+/-SD) to achieve normal neutrophil
level (>0.5 X 10/9/l) after day 0 of BMT.. . . . . . . . . . . . . . . . . . . . . . . . . 71
Analysis 4.8. Comparison 4 PN vs enteral feeding studies, Outcome 8 Actual numbers of patients who have completed the
study and survived to the 100th day post BMT.. . . . . . . . . . . . . . . . . . . . . . . 72
Analysis 4.9. Comparison 4 PN vs enteral feeding studies, Outcome 9 Actual number of patients who have completed the
study and survived beyond day 200 post BMT.. . . . . . . . . . . . . . . . . . . . . . . 73
Analysis 5.1. Comparison 5 Oral eicosapentaenoic acid supplementation versus nil, Outcome 1 Numbers not developing
graft versus host disease. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 73
74ADDITIONAL TABLES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
75APPENDICES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
76FEEDBACK . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
77WHAT’S NEW . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
77HISTORY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
79CONTRIBUTIONS OF AUTHORS . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
79DECLARATIONS OF INTEREST . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
79NOTES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
79INDEX TERMS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
iiNutrition support for bone marrow transplant patients (Review)
Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
[Intervention Review]
Nutrition support for bone marrow transplant patients
Susan M Murray1, Sima Pindoria2
1Royal College of Physicians, London, UK. 2Centre for Paediatric Epidemiology and Biostatistics, Institute of Child Health, London,
UK
Contact address: Susan M Murray, Royal College of Physicians, London, UK. [email protected].
Editorial group: Cochrane Pain, Palliative and Supportive Care Group.
Publication status and date: Edited (no change to conclusions), published in Issue 5, 2014.
Review content assessed as up-to-date: 30 April 2008.
Citation: Murray SM, Pindoria S. Nutrition support for bone marrow transplant patients. Cochrane Database of Systematic Reviews
2009, Issue 1. Art. No.: CD002920. DOI: 10.1002/14651858.CD002920.pub3.
Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
A B S T R A C T
Background
This is an update of the original Cochrane review published in Issue 2, 2002. Bone marrow transplantation involves administration of
toxic chemotherapy and infusion of marrow cells. After treatment, patients can develop poor appetite, mucositis and gastrointestinal
failure, leading to malnutrition. To prevent this, parenteral nutrition (PN) support is often first choice but is associated with increased
risk of infection. Enteral nutrition (EN) is an alternative, as is addition of substrates.
Objectives
To determine efficacy of EN or PN support for patients receiving bone marrow transplant.
Search methods
Search of The Cochrane Library, MEDLINE, EMBASE and CINAHL in November 2000 and subsequently June 2006.
Selection criteria
RCTs that compared one form of nutrition support with another, or control, for bone marrow transplant patients.
Data collection and analysis
Twenty nine studies were identified. Data were collected on participants’ characteristics; adverse effects; neutropaenia; % change in
body weight; graft versus host disease; and survival.
Main results
In two studies (82 participants) glutamine mouthwash reduced number of days patients were neutropenic (6.82 days, 95%CI (1.67
to 11.98) P = 0.009) compared with placebo. Three studies reported (103 participants) that patients receiving PN with glutamine had
reduced hospital stay, 6.62 d (95%CI 3.47 to 9.77, P = 0.00004) compared with patients receiving standard PN. However, in the
update a further study was added (147 participants) which altered the pooled results: duration in hospital may be increased for those
who receive PN with additional glutamine - 0.22 days (95%CI (1.29 to 1.72). Two other studies reported that (73 participants) patients
receiving PN plus glutamine had reduced incidence of positive blood cultures (OR 0.23, 95%CI 0.08 to 0.65, P = 0.006) compared to
those receiving standard PN. However, a study from the update (113 participants in total) showed the odds of having a positive blood
culture have increased but are still less likely if the patient receives PN with glutamine compared to standard PN (OR 0.46, 95%CI
0.20 to 1.04). When patients were given PN versus IV hydration, (25 participants) patients receiving PN had a higher incidence of
line infections (OR 21.23, 95%CI 4.15 to 108.73, P = 0.0002) compared to those receiving standard IV fluids. The update identified
1Nutrition support for bone marrow transplant patients (Review)
Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
one study which recognised that (55 participants) those who received IV were likely to spend less time in hospital, 3.30 days (95%CI
-0.38 to 6.98, P = 0.08), although this result was not significant. As reported in the original review there remains no evaluable data to
properly compare PN with EN.
Authors’ conclusions
In this update an additional study that compared PN and Glutamine versus standard PN showed that the certain benefits of parenteral
nutrition with added glutamine compared to standard PN for reducing hospital stay are no longer definite. When PN with glutamine
is compared with standard PN, patients may not leave hospital earlier, but do have reduced incidence of positive blood cultures, than
those receiving standard PN. Where possible use of intravenous fluids and oral diet should be considered as a preference to parenteral
nutrition, however, in the event of a patient suffering severe gastrointestinal failure even with a trial of enteral feeding, PN with the
addition of glutamine could be considered.
P L A I N L A N G U A G E S U M M A R Y
Nutritional support for patients who have had a bone marrow transplant
Bone marrow transplant patients can experience prolonged poor appetite with vomiting and diarrhoea. Malnutrition is a consequence.
To prevent this, patients can receive nutritious fluids orally or via a nasogastric tube, or intravenously as parenteral nutrition. The
benefits of either route are unclear. Studies were found that compared these interventions but missing data prevents proper assessment
of the benefits. However, the limited data available indicates that when patients undergo bone marrow transplantation and are given
intravenous fluids and are encouraged to have an oral diet they are less likely to experience infections and are more likely to go home
earlier than if they are given standard parenteral nutrition routinely. In the event that patients nutritional intake is inadequate because
of an inadequate oral intake or because they are unable to tolerate tube feeding and are given parenteral nutrition with added glutamine
they are likely to have less infections but may not necessarily leave hospital earlier.
B A C K G R O U N D
Patients receiving bone marrow transplantation (BMT) for malig-
nant and non malignant diseases are prone to varying degrees of
gastrointestinal failure. The main symptoms are prolonged vomit-
ing, diarrhoea and at worst but rarely, intestinal obstruction. The
cause of gastrointestinal failure is unclear but BMT patients in
addition to receiving chemotherapy, which is toxic to the gut and
destroys the host’s marrow cells, receive either donor marrow cells
(allogeneic) or their own marrow cells (autologous). The receipt
of marrow increases the potential complication of graft versus host
disease and infection which can magnify the difficulties in the
nutritional management of these patients. Many patients experi-
ence a significant reduction in appetite and therefore calorie intake
within a few days of admission to hospital which is frequently as-
sociated with a significant decrease in body weight. Consequently
optimum delivery of nutrition support often becomes essential
early on in the course of treatment for a BMT.
Traditionally, parenteral nutrition (PN), which is the adminis-
tration of intravenous nutrition given to bypass the alimentary
canal when it is not functioning adequately, has been given as
the first option of nutrition support to BMT patients (Weisdorf
1984; Herrmann 1993). This is in preference to enteral nutrition
(EN) which is the delivery of oral or tube feeding via any route
connected to the gastrointestinal tract. The reasons for this are
probably because routine insertion of long lines has enabled PN
to be delivered relatively effortlessly and also because there was a
belief that enteral feeding is an unacceptable form of ’force feed-
ing’ (Rickard 1980) and may not be well tolerated. The advan-
tages of either of these types of nutrition support in BMT patients
are not clear but PN is associated with more complications e.g.
increased line infections and reduction in gut mucosal integrity
(Kudsk 1994) which may lead to longer hospitalisation. There are
some reports from prospective studies, on the successes of enteral
feeding in these types of patients (Papadopoulou 1997). Several
authors would now argue that enteral feeding should always be
considered as the first option of nutrition support for these patients
(Mercadante 1998a; Iestra 1999). However, there have been few
attempts from prospective randomised controlled trials to prove
the benefits of enteral or parenteral nutrition support for BMT
patients.
2Nutrition support for bone marrow transplant patients (Review)
Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Two authors, Lipman 1991b and Klein 1994, have previously, in-
dependently, reviewed the efficacy of nutrition support in cancer
patients. Both authors examined controlled trials of various forms
of nutrition support in a variety of patients receiving therapy for
cancer and BMT. They reported that nutrition support did not
appear to consistently improve nutritional parameters and was
not clinically effective in improving other important outcomes
for cancer patients. However, there was some evidence from two
randomised controlled trials (RCTs) (Szeluga 1987 and Weisdorf
1987) that BMT patients, survival rate improved when given PN
but infection rates and costs were higher for those receiving PN
compared to those receiving EN. Both of these reviews have been
assessed by peer reviewers from the Centre for Reviews and Dis-
semination, York, UK, (reviews on The Cochrane Library). They
commented that, whilst the conclusions of these reviews may re-
flect the benefits of nutrition support for patients receiving treat-
ment for cancer, they were unable to determine the completeness
of the reviews because they did not satisfy the methodological cri-
teria that has been proposed for scientific overviews.
Since then, and in the last decade, there has been increasing inter-
est in the addition of glutamine to both enteral and parenteral so-
lutions. Glutamine is considered to be a non-essential amino acid
which may become an essential amino acid for the catabolic sick
patient. It may also have an affect on preventing gut atrophy and
also enhance immune function (Sax 1992), both of which are po-
tentially debilitating problems for BMT patients. As a result there
have been an increasing number of controlled and uncontrolled
trials reporting the benefits of glutamine in BMT patients.
Since the treatment for BMT patients differs significantly from
cancer patients because of the receipt of marrow cells, this review
(unlike Lipman 1991b and Klein 1994) has focused specifically
on BMT patients. The aim is to assess the effectiveness of any type
of feeding regime that has been compared in patients receiving
BMT.
O B J E C T I V E S
To determine the efficacy of any form of enteral or parenteral nu-
trition support given to patients receiving bone marrow transplan-
tation. Efficacy will be considered in terms of time in hospital,
complications, change in nutritional status e.g. change in body
weight, and survival.
M E T H O D S
Criteria for considering studies for this review
Types of studies
Any randomised (strict format of patient allocation to experimen-
tal group e.g. centralised randomisation) or quasi randomised (e.g.
alternate patient admissions) controlled trial.
Types of participants
Participants of all ages receiving any type of bone marrow trans-
plant.
Types of interventions
RCTs comparing one type or mode of nutrition support (enteral
or parenteral) with another or with an intravenous solution of
glucose/saline. Where enteral nutrition (EN) is the delivery of any
substance of nutritional value in solid or liquid form (and can
include usual food intake) that passes any part of the digestive tract,
regardless of the method of delivery e.g. orally or via a tube (e.g.
nasogastric, gastrostomy, jejunostomy). Parenteral nutrition (PN)
is the administration of nutritional liquids containing a minimum
of glucose and amino acids which is administered through the
central or peripheral venous system and therefore bypasses the
gastrointestinal tract.
Types of outcome measures
Defined outcome measures considered most important are listed
below.
Primary outcomes
• Hospital duration e.g. mean duration admission to
discharge or from day 0 to discharge home.
• Mucositis - mean number of days patient groups had some
degree of mucositis from start to end of study.
• GVHD - number of patients who developed > grade 2 graft
versus host disease (GVHD).
• Nutritional status -difference in mean % change in body
weight from start to end of study between the trial groups.
• Duration of nutritional intervention/time to resume
adequate oral intake.
• Neutropaenia mean number of days to achieve normal
neutrophil level after day of BMT, day 0.
• Line infection - number of patients who developed line
infections from start to the end of the study.
• Number with positive blood cultures.
• Survival to 100 day - actual numbers who have completed
study surviving to the 100th day post-BMT.
• Survival beyond 100 days - actual numbers who have
completed study surviving beyond day 100 or two year survival.
3Nutrition support for bone marrow transplant patients (Review)
Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Secondary outcomes
• Vomiting - mean number of days patients had >/= than 3
vomits/day from start to end of study.
• Diarrhoea - mean number of days patients had >/= 3 bowel
motions /day from start to end of study.
• Veno Occlusive Disease - number of patients who developed
veno occlusive disease (VOD) actual number/per group.
• Liver function disturbances - number of patients who had
an abnormal bilirubin level from the start of study to end of
study.
• Hepatomegaly - number of patients who developed
hepatomegaly from start to end of study.
• Albumin - mean change in albumin from start to end of
study between the trial groups.
• Pre-Albumin - mean change in pre-albumin from start to
end of study between the trial groups.
• Engraftment - mean duration for each group to achieve
engraftment, post-BMT (from day 0).
Search methods for identification of studies
Studies were identified by searching The Cochrane Library (Issue
4, 2000, subsequent search Issue 2, 2006), MEDLINE (1966 to
2000, subsequent search June 2006), EMBASE (1988 to 2000,
subsequent search June 2006) and CINAHL (1982 to 2000, sub-
sequent search June 2006). An example of the search strategy used
and adapted for all databases searched can be seen in Appendix 1.
Reference lists of identified trials and conference proceedings were
also searched for relevant studies.
A search strategy (with no randomised controlled trial (RCT)
filter) was designed for identifying trials from the following
databases: The Cochrane Library, MEDLINE, EMBASE and
CINAHL.
Hand searching included nutrition and bone marrow transplant
conference proceedings, reference lists of papers found through
electronic searching, and consultation with experts.
Data collection and analysis
Study selection
Studies identified by the computerised search were scanned by
the lead review author and all apparently relevant studies were
retrieved. These were assessed independently by the lead review
author (SM) and co-author (SP) for inclusion or exclusion in the
review according to the pre-specified inclusion criteria. A data ex-
traction form was designed and used to record data on partici-
pants, interventions and outcomes as described in the ’Criteria
for considering studies for this review’ section above. Differences
between review authors’ extracted results were resolved by discus-
sion.
Correspondence with authors
Many of the authors of included studies either did not report all
of the desired outcomes of interest or presented them in a format
unsuitable for meta-analysis. Where it was possible to locate the
authors of the main studies, a standard letter requesting further
information was sent.
Statistical methods
Outcomes measured as continuous data (time in hospital, change
in nutritional status) were analysed using means and mean dif-
ferences with their corresponding standard deviations and stan-
dard errors, and reported with 95% confidence intervals (CIs).
Dichotomous data were analysed using odds ratios and reported
with 95% CIs. Where meta-analyses were possible, summary es-
timates of measures of relevant outcomes with 95% CIs were re-
ported using a fixed-effect model.
Statistical heterogeneity was tested using a Chi square test. Where
the P value was less than or equal to 0.05 this indicated significant
heterogeneity, and If this is the case a random effects model will
be used to derive a summary statistic with 95% CIs.
It was planned to investigate clinical heterogeneity by performing
analyses on the following sub-groups: adults versus children (0 to
18 years); disease type; transplant type. However, insufficient data
were available.
Similarly, there were insufficient data to:
• assess the effect of the type of allocation concealment;
• assess the effect of loss to follow-up;
• calculate a ’number needed to treat to benefit’ (NNT).
R E S U L T S
Description of studies
In the first review thirty five studies were identified of which 11
were excluded. Two review authors extracted data from 24 studies
which fulfilled all the inclusion criteria; 16 were allocated to four
interventions: oral glutamine versus placebo; PN and glutamine
versus standard PN; PN versus IV hydration; PN versus EN. Eight
other studies compared a variety of other interventions that could
not be grouped. The details of trials in each group are listed below.
For the update of this review 17 studies were identified, 12 were
excluded and five were included. Three of the five included studies
were allocated to either oral glutamine versus placebo (1); PN and
glutamine versus standard PN (1); PN versus IV hydration (1).
4Nutrition support for bone marrow transplant patients (Review)
Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Two other studies were separate interventions and could not be
grouped.
Consequently in this review there are 29 included studies -19 stud-
ies have been allocated to four main types of nutritional interven-
tions and ten studies remain ungrouped since they individually
assess other types of interventions.
Data were collected on participants’ characteristics; adverse effects;
neutropaenia; % change in body weight; graft versus host disease;
and survival.
Oral glutamine versus placebo
Following the original review when there were four studies, one
further study Aquino 2005 was identified in the update. The five
trials (Aquino 2005; Coghlin Dickson 2000; Jebb 1995; Schloerb
1999) compare oral glutamine versus placebo and include 463
participants. In one trial by Schloerb 1999, participants failing to
take the oral supplement were given either PN with glutamine
or standard PN according to which group the participants were
originally randomised. Despite this, the results of this study were
allocated to this group because the original allocation was to oral
glutamine or placebo.
Parenteral nutrition with glutamine versus standard
parenteral nutrition
In the original review there were seven publications of trials com-
paring PN with glutamine versus standard PN. Four of these were
duplicate reports of one original study by Ziegler 1992. They were
MacBurney 1994; Scheltinga 1991; Ziegler 1998; Young 1993.
Data from studies by Ziegler 1992; Brown 1998; Schloerb 1993
were used. For the update of this review another study Pytlik 2002
was found and merged with the data from the three studies previ-
ously mentioned, totaling 148 participants.
Standard parenteral nutrition versus intravenous
hydration
Two trials involving a total of 166 participants were identified in
the first review (Lough 1990; Weisdorf 1987). A further study
Roberts 2003a was identified in the update and has been merged
with these studies. The total number of participants in this group
of studies is 221.
Parenteral nutrition versus enteral nutrition
In the first review one full report and two abstracts (Cope 1997;
Szeluga 1987; Young 1997), including a total of 144 participants,
were identified. During the update of this review one other study
comparing PN versus EN (Hopman 2003) was found but the
outcome data could not be used since it appeared that some of
the outcome data was obtained from participants who were not
randomised into the study.
The other eight trials identified in the first review (Aldamiz 1996;
Charuhas 1997; Jimenez 1999; Lenssen 1987; Lenssen 1998;
Malhotra 1996; Mulder 1989; Muscaritoli 1998) and two others in
the update (Santos 2001; Takatsuka 2002) compared a miscellany
of nutritional interventions, and could not be allocated to the
above groups.
Risk of bias in included studies
Three aspects of study methodology were addressed:
• allocation concealment (Mulrow 1997);
• blinding (although this was not considered to be a real
threat to biasing the results since the main outcomes were
considered to be objective measures);
• loss to follow up.
The details of these can be viewed in Additional Table 1.
Effects of interventions
Although five additional studies were added to the update of this
review many of the outcomes in these studies could not be in-
cluded in the data analysis since they were either presented in het-
erogenous units or were not relevant to the objectives of this re-
view.
The results of the four main groups of comparisons of nutrition
support are listed below.
Oral glutamine versus oral placebo
For a number of the main outcomes adequate data were provided
by Jebb 1995 and Schloerb 1999 only.
The use of an oral placebo mouth wash, resulted in a significant
reduction in days to achieve a normal neutrophil level (6.82 days,
95% CI (1.67 to 11.98) P = 0.009) compared to an oral glutamine
mouth wash.
The results for hospital duration, change in body weight, duration
of nutritional intervention, numbers with positive blood cultures
were not significant and also remained not significant when the
additional data retrieved in the update of this review from Aquino
2005 for survival at 100 days was added.
PN and glutamine versus standard PN
In the first review data was provided by either two or all three au-
thors on all the main outcomes of interest except line infections.
For the update, outcome data from the study reported by Pytlik
2002 for hospital duration, mean cumulative mucositis score, du-
ration that nutritional intervention (PN) was given and numbers
of participants with positive blood cultures were added. In the
first review one of the most significant outcomes was that, for par-
ticipants receiving glutamine enriched PN, hospital duration was
5Nutrition support for bone marrow transplant patients (Review)
Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
reduced by 6.62 days (weighted mean difference) with 95% CI
-9.77 to 3.47, P = 0.00004. However, with the addition of the
data from Pytlik 2002 it appears that the possibility that PN with
added glutamine could reduce hospital admission is no longer ap-
parent since the pooled result suggests that participants given PN
with Glutamine (although not significant) have an increase of 0.22
days in hospital with 95% CI -1.29 to 1.72, P = 0.78 compared
with participants given standard PN. Despite the additional data
added in from Pytlik 2002 the likelihood of these participants de-
veloping positive blood cultures remains less compared to those
on standard PN, although this is not significant. The odds ratio is
0.46 with a 95% CI 0.20 to 1.04, P = 0.06.
For the first review and with this update no significant difference
was found in the treatment affect for either PN and glutamine or
standard PN for severity of mucositis, change in body weight, dura-
tion parenteral nutrition required, incidence of > grade 2 GVHD,
duration of neutropaenia and survival at 100 days.
PN versus IV hydration
Like the first review Lough 1990; Weisdorf 1987 and now Roberts
2003a considered a number of similar outcomes, however a num-
ber of the outcomes within these studies are expressed in a variety
of different units that has not always made it possible to pool all the
outcomes of interest into a meta-analysis. In the first review Lough
1990 provided data on a number of outcomes of interest, some
showing significant differences between the PN and IV hydration
group. His data showed that the odds of having a line infection
when given PN compared to IV hydration were 21.23 than for
participants receiving IV hydration (95% CI 4.15 to 108.73, P
= 0.0002). Also, the mean percentage change in albumin for the
IV hydration group showed surprisingly significant increases in
albumin concentrations compared to the PN group and this was
also found with in the study by Roberts 2003a. (The pooled mean
difference was -3.72 (95% CI -5.96 to -1.49), P = 0.001). Lough
1990 also indicated that for percentage change in body weight
PN was more beneficial than IV hydration for preventing weight
loss and this was also identified in the study by Roberts 2003a.
The weighted mean difference for percentage change in weight
in the first review was 2.76 (95% CI 1.26 to 4.26, P = 0.0003)
and with the additional data from Roberts 2003A the weighted
mean difference was 2.81 (95%CI 1.34 to -4.29). There was no
significant difference in survival at 200 days post BMT. Lough
1990 showed that the odds of surviving this long post BMT were
2.10 (95%CI 0.48 to 9.18, P = 0.3) favouring PN over IV hydra-
tion (29 participants). Roberts 2003a provided data on survival at
two years post BMT and five years post BMT but this could not
be merged with the survival data provided by Lough 1990 since
it was estimated at different time points. The data from Roberts
2003a showed that the probability of survival at two years was
higher for the participants who received PN, 74%, compared to
57% for those who were in the group randomised to receive oral
diet and or intravenous hydration. However at 5 years post BMT
the probability of survival in either the PN or the oral diet/IV
hydration group was the same at 38%.
PN versus EN
For the update of this review one other RCT (Hopman 2003) was
found but could not be included since the outcome data included
data from participants who were not originally randomised into
the study. No further studies were included for this part. There-
fore the findings reported in the first review remain that for the
three studies originally reported, a number of outcomes of inter-
est were presented but none of the data could be utilised. Data
provided by Szeluga 1987 on change in body weight indicated
that participants receiving parenteral nutrition were more likely
to gain weight with this form of nutrition support. However, the
crossover of participants from one group to another during the
study provided uncertainty on the clarity of the data presented
in the paper. Young 1997 presented similar data as median and
ranges, which could not be utilised but also favoured parenteral
nutrition for maintaining body weight, although the results were
not significant. All three authors (Cope 1997, Szeluga 1987 and
Young 1997) reported measuring hospital duration but the data
were inadequate for analysis.
Cope 1997 and Young 1997 both suggested that length of hos-
pitalisation was significantly shorter in the enteral feeding group,
whilst Szeluga 1987 implied that there was no significant differ-
ence between either group.
Since all the other included studies could not be grouped and had
low power, no comprehensive assessment of the results could be
made. If future randomised controlled trials of studies of these
interventions are performed, it may then be possible to group some
of the outcomes.
D I S C U S S I O N
This review had wider inclusion criteria than those on nutrition
support and cancer by Lipman 1991b and Klein 1994, but in-
cluded only BMT patients. The identification of 24 RCTs in the
first review and now a further five in the update of this review
suggests there is a keen interest in identifying the best mode of
nutrition support for BMT patients.
In the first review we reported that for oral glutamine versus oral
placebo trials, data from two out of four studies only could be
used. This reduced the pooled sample size significantly. Most of
the results were inconclusive for the outcomes of interest. One of
the authors of a trial with no usable data (Coghlin Dickson 2000)
concluded that the benefits of oral glutamine were inconclusive
and that further trials are required. In the first review we suggested
that since the studies of Coghlin Dickson 2000 and Anderson
6Nutrition support for bone marrow transplant patients (Review)
Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
1998 included 251 participants, it would have been beneficial if the
missing data from these studies could be retrieved to increase the
pooled sample size and improve the reliability of detecting a true
affect of the intervention, before further studies are performed. For
the update of this review one further study by Aquino 2005 which
included children (whose mean age ranged from 9-10 years) has
been added to this group of studies and whilst there is interesting
data provided most of this could not be pooled with the exception
of one outcome - survival to the 100th day. For this it appears
that the children who received the placebo were more likely to
survive to the 100th day post BMT than those who received the
intervention but this result and the overall pooled result is not
significant.
In the first review for the PN and glutamine versus standard PN
trials, we commented on the positive effect that PN with Glu-
tamine had on reducing the incidence of positive blood cultures
and hospital duration. However the addition of data in the sec-
ond review from Pytlik 2002, with 40 additional participants now
suggests that participants given PN with Glutamine may actually
have an increased hospital duration compared to those given stan-
dard PN, although it must be emphasised that this is not signifi-
cant. However the likelihood that patients will have more positive
blood cultures if they are not given PN with Glutamine remains
consistent but the data for this is also not significant. It would
now seem that the benefits of giving BMT patients who need PN
(because of an inadequate oral intake), PN with Glutamine is not
clear.
For the studies that compared parenteral nutrition versus intra-
venous hydration and following the update of this review the ben-
efits of PN remain unclear because of insufficient data. The addi-
tion of data from Roberts 2003a showed further that patients given
PN are less likely to experience a large decrease in body weight and
hence their nutritional status is perhaps better maintained. Data
on the incidence of line infections remain the same as presented
in the study by Lough 1990 who showed that there was a higher
incidence of line infections associated with parenteral nutrition
compared to the intravenous hydration group, and reminds us that
parenteral nutrition should be administered with caution when
there is evidence of poor tolerance of enteral feed and prolonged
gastrointestinal failure.
In the first review we reported that the results from the parenteral
nutrition versus enteral nutrition trials were inconclusive due to
inadequate data. For the update of this review we identified a
further trial that compared the benefits of PN versus EN, however,
this was excluded because there was not a proper intention to
treat analysis. The authors of these studies have hinted that enteral
nutrition when compared to PN may have an affect on reducing
hospital duration which could have important benefits to patients
as well as cost saving advantages, suggesting the need for a large
randomised controlled trial to compare parenteral nutrition versus
enteral nutrition.
A U T H O R S ’ C O N C L U S I O N S
Implications for practice
Readers of the original review are advised to re-read this update as
the conclusions have changed.
• Routine use of parenteral nutrition and glutamine for bone
marrow patients predicted to have prolonged gastrointestinal
failure, could be considered.
• Caution in the routine use of PN is still required because of
the increased risk of line infection
• Where possible use of intravenous fluids and oral diet
should be considered as a preference to parenteral nutrition,
however, in the event of a patient suffering severe gastrointestinal
failure even with a trial of enteral feeding, PN with the addition
of glutamine could be considered.
Implications for research
For this update 17 more studies were identified in June 2006
and five studies were included. Consequently there are now 29
included studies -19 studies are allocated to four main sub reviews
and ten studies remain ungrouped. To conclude:
• The benefits of oral glutamine mouth washes compared to
oral placebo remain unclear and further studies or the provision
of complete data from the studies already performed are required.
• The benefits of glutamine in PN compared to standard PN
are now not certain.
• For patients who receive PN and glutamine there no longer
appears to be a reduction in hospital stay, but they may have a
reduced incidence of positive blood cultures.
• The benefits of enteral nutrition in preference to PN are
still not clear, reflecting an urgent need for a good quality
prospective RCTs in this area.
A C K N O W L E D G E M E N T S
• Systematic Reviews Training Unit at the Institute of Child
Health, London for providing Susan Murray with funding to
undertake training in systematic reviews.
7Nutrition support for bone marrow transplant patients (Review)
Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
• Professor PR Schloerb and Dr CH Poynton kindly
provided unpublished data for this review.
• I acknowledge Peter Katz input in updating the search
strategy for the updated review who is sadly now deceased.
R E F E R E N C E S
References to studies included in this review
Aldamiz 1996 {published data only}
Aldamiz EL, Bachiller MP, Ariz MC, Gimenez A, Barcia
MJ, Marin M. Continuous versus cyclic parenteral nutrition
during bone marrow transplantation: Assessment and
follow-up. Clinical Nutrition 1996;15(6):333–6.
Anderson 1998 {published data only}
Anderson PM, Ramsay NK, Shu XO, Rydholm N,
Rogosheske J, Nicklow R, et al.Effect of low-dose oral
glutamine on painful stomatitis during bone marrow
transplantation. Bone Marrow Transplant 1998;22(4):
339–44. [: 1]
Aquino 2005 {published data only}∗ VM Aquino, AR Harvey, JH Garvin, KT Godder, ML
Nieder, RH Adams, et al.A double blind randomized
placebo-controlled study of oral glutamine in the prevention
of mucositis in children undergoing hematopoietic stem cell
transplantation: a pediatric blood and marrow transplant
consortium study. Bone Marrow Transplantation 2005;36:
611–6.
Brown 1998 {published data only}
Brown SA, Goringe A, Fegan C, Davies SV, Giddings J,
Whittaker JA, et al.Parenteral glutamine protects hepatic
function during bone marrow transplantation. Bone
Marrow Transplant 1998;22(3):281–4.
Charuhas 1997 {published data only}
Charuhas PM, Fosberg KL, Bruemmer B, Aker SN,
Leisenring W, Seidel K, Sullivan KM. A double-blind
randomized trial comparing outpatient parenteral nutrition
with intravenous hydration: effect on resumption of oral
intake after marrow transplantation. Journal of Parenteral
and Enteral Nutrition 1997;21(3):157–61.
Coghlin Dickson 2000 {published data only}
Coghlin Dickson T, Wong RM, Negrin RS, Shizuru
JA, Johnston LJ, Hu WW, et al.Effect of oral glutamine
supplementation during bone marrow transplantation.
Journal of Parenteral and Enteral Nutrition 2000;24(2):61–6.
Cope 1997 {published data only}
Cope FO. Prophylactic enteral support to BMT patients
reduces length of hospital stay, improves GI integrity and
nutritional status, and reduces intake requirements required
for positive outcome. Procedures of the Annual Meeting of
the American Society for Clinical Oncology. 1997.
Jebb 1995 {published data only}
Jebb SA, Marcus R, Elia M. A pilot study of oral glutamine
supplementation in patients receiving bone marrow
transplants. Clinical Nutrition 1995;14(3):162–5.
Jimenez 1999 {published data only}
Jimenez JF, Ortiz LC, Garcia GJ, Garnacho MJ, Rodriguez
FJ, Espigado TI. Prospective, comparative study of different
amino acid and lipid solutions in the parenteral nutrition
of patients subjected to a bone marrow transplantation.
Nutricion Hospitalaria 1999;14(2):57–66.
Lenssen 1987 {published data only}
Lenssen P, Cheney CL, Aker SN, Cunningham BA,
Darbinian J, Gauvreau JM, Barale KV. Intravenous
branched chain amino acid trial in marrow transplant
recipients. Journal of Parenteral and Enteral Nutrition 1987;
11(2):112–8.
Lenssen 1998 {published data only}
Lenssen P, Bruemmer BA, Bowden RA, Gooley T, Aker
SN, Mattson D. Intravenous lipid dose and incidence of
bacteremia and fungemia in patients undergoing bone
marrow transplantation. American Journal of Clinical
Nutrition 1998;67(5):927–33.
Lough 1990 {published data only}
Lough M, Watkins R, Campbell M, Carr K, Burnett
A, Shenkin A. Parenteral nutrition in bone marrow
transplantation. Clinical Nutrition 1990;9(2):97–101.
MacBurney 1994 {published data only}
MacBurney M, Young LS, Ziegler TR, Wilmore DW. A
cost-evaluation of glutamine-supplemented parenteral
nutrition in adult bone marrow transplant patients. Journal
of American Dietetics Association 1994;94(11):1263–6.
Malhotra 1996 {published and unpublished data}
Malhotra D, DeMeo D, Kruger A, Rooney D, Holmes
E, Poe L, et al.Oral elemental nutrition improves
gastrointestinal integrity in patients undergoing bone
marrow transplantation. Proceedings of Asco Vol. 1996;
Vol. 15:450. [: 13]
Mulder 1989 {published data only}
Mulder PO, Bouman JG, Gietema JA, Van Rijsbergen H,
Mulder NH, Van der Geest S, et al.Hyperalimentation in
autologous bone marrow transplantation for solid tumors.
Comparison of total parenteral versus partial parenteral plus
enteral nutrition. Cancer 1989;64(10):2045–52.
Muscaritoli 1998 {published data only}
Muscaritoli M, Conversano L, Torelli GF, Arcese W,
Capria S, Cangiano C, et al.Clinical and metabolic effects
8Nutrition support for bone marrow transplant patients (Review)
Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
of different parenteral nutrition regimens in patients
undergoing allogeneic bone marrow transplantation.
Transplantation 1998;66(5):610–6.
Pytlik 2002 {published data only}
Pytlik R, Benes P, Patorkova M, Chocenska E, Gregora E,
Prochazka B, et al.Standardised parenteral alanyl-glutamine
dipeptide supplementation is not beneficial in autologous
transplant patients: a randomized, double-blind, placebo
controlled study. Bone Marrow Transplantation 2002;30:
953–961.
Roberts 2003a {published data only}∗ Roberts S, Miller J, Pineiro L, Jennings L. Total parenteral
nutrition vs oral diet in autologous hematopoietic cell
transplant recipients. Bone Marrow Transplantation 2003;
32:715–21.
Santos 2001 {published data only}∗ Santos P, Lourenco R, Camilo ME, Oliveira AG, Figueira
I, Pereira ME, et al.Parenteral nutrition and cyclosporine:
do lipids make a difference? A prospective randomised cross
over trial. Clinical Nutrition 2001;20(1):31–36.
Scheltinga 1991 {published data only}
Scheltinga MR, Young LS, Benfell K, Bye RL, Ziegler TR,
Santos AA, et al.Glutamine-enriched intravenous feedings
attenuate extracellular fluid expansion after a standard stress.
Annals of Surgery 1991;214(4):385–95.
Schloerb 1993 {published data only}
Schloerb PR, Amare M. Total parenteral nutrition with
glutamine in bone marrow transplantation and other clinical
applications (a randomized double-blind study). Journal of
Parenteral and Enteral Nutrition 1993;17(5):407–13.
Schloerb 1999 {published data only}
Schloerb PR, Skikne BS. Oral and parenteral glutamine in
bone marrow transplantation: a randomized, double-blind
study. Journal of Parenteral and Enteral Nutrition 1999;23
(3):117–22.
Szeluga 1987 {published data only}
Szeluga DJ, Stuart RK, Brookmeyer R, Utermohlen
V, Santos GW. Nutritional support of bone marrow
transplant recipients: a prospective, randomized clinical
trial comparing total parenteral nutrition to an enteral
feeding program. Cancer Research 1987;47(12):3309–16.
Takatsuka 2002 {published data only}∗ Takatsuka H, Takemoto Y, Iwata N, Suehiro A, Hamano
T, Okamoto T, Kanamaru A. Oral eicosapentaenoic acid
for complications of bone marrow transplantation. Bone
Marrow Transplantation 2001;28:769–74.
Weisdorf 1987 {published data only}
Weisdorf SA, Lysne J, Wind D, Haake RJ, Sharp HL,
Goldman A, et al.Positive effect of prophylactic total
parenteral nutrition on long-term outcome of bone marrow
transplantation. Transplantation 1987;43(6):833–8.
Young 1993 {published data only}
Young LS, Bye R, Scheltinga M, Ziegler TR, Jacobs DO,
Wilmore DW. Patients receiving glutamine-supplemented
intravenous feedings report an improvement in mood.
Journal of Parenteral and Enteral Nutrition 1993;17(5):
422–7.
Young 1997 {published and unpublished data}
Young M, Stanford J, Walker DJ, Frost G. Preliminary report
of the efficacy of nasogastric feeding in allogeneic adult bone
marrow transplant patients. Original Communications of
the Nutrition Society Original Communications of the
Nutrition Society 1997. [: 24]
Ziegler 1992 {published data only}
Ziegler TR, Young LS, Benfell K, Scheltinga M, Hortos K,
Bye R, et al.Clinical and metabolic efficacy of glutamine-
supplemented parenteral nutrition after bone marrow
transplantation. A randomized, double-blind, controlled
study. Annals of Internal Medicine 1992;116(10):821–8.
Ziegler 1998 {published data only}
Ziegler TR, Bye RL, Persinger RL, Young LS, Antin JH,
Wilmore DW. Effects of glutamine supplementation on
circulating lymphocytes after bone marrow transplantation:
a pilot study. American Journal of Medical Sciences 1998;315
(1):4–10.
References to studies excluded from this review
Clemens 1997 {published data only}
Clemens MR, Waladkhani AR, Bublitz K, Ehninger G,
Gey KF. Supplementation with antioxidants prior to bone
marrow transplantation. Wien Klin Wochenschr 1997;109
(19):771–6.
Cohen 1996 {published data only}
Cohen D. Nutrition management of gastrointestinal graft-
versus-host disease following bone marrow transplantation.
Support Line 1996;5:13–5.
Duggan 2004 {published data only}
Duggan C, Stark A, Auestad N, Collier S, Fulhan J,
Gura K, et al.Glutamine Supplementation in Infants with
Gastrointestinal Disease: A randomized placebo controlled
pilot trial. Nutrition 2004;20:752–6.
Ford 1992 {published data only}
Ford EG. Clinical comparison of tolerance to elemental
or polymeric enteral feedings in the postoperative patient.
Journal of the American College of Nutrition 1992;11(1):
11–6.
Hopman 2003 {published data only}
Hopman G, Pena E, le Cessie S, van Weel MH, Vossen
JMJJ, Mearin ML. Tube feeding and Bone Marrow
Transplantation. Medical and Paediatric Oncology 2003;40
(6):375–9.
Klein 1994 {published data only}
Klein S, Koretz RL. Nutrition support in patients with
cancer: what do the data really show?. Nutrition in Clinical
Practice 1994;9(3):91–100.
Lipman 1991a {published data only}
Lipman TO. Grains or veins: Is enteral nutrition really
better than parenteral nutrition? A look at the evidence.
Journal of Parenteral and Enteral Nutrition 1998;60(22/3):
167–82.
9Nutrition support for bone marrow transplant patients (Review)
Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Mercadante 1998a {published data only}
Mercadante S. Parenteral versus enteral nutrition in cancer
patients: Indications and practice. Supportive Care in
Cancer 1998;6(2):85–93.
Mobrahan 1992 {published data only}
Mobrahan S. Glutamine: A conditionally essential nutrient
or another nutritional puzzle. Nutrition Reviews 1992;50
(11):331–3.
Piccirillo 2002 {published data only}
Piccirillo N, S De Matteis L, Laurenti P, Chiusolo F, Sora
S, Rutella S, et al.Glutmine enriched parenteral nutrition
after autologous peripheral blood stem cell transplantation:
effects on immune reconstitution and mucositis. Bone
Marrow Transplantation 2002;29:Suppl S 21.
Piccirillo 2004 {published data only}
N Piccirillo, S De Matteis, F Sora, L Laurenti, P Chiusolo,
G Leone, S Sica. Glutamine parenteral supplementation in
stem cell transplant. Bone Marrow Transplantation 2004.
Poznarova 2003 {published data only}
Poznarova A, Horacek J, Zac P, Kmonicek M, Maly J. A
randomised double blind comparative study of parenteral
nutritional support with or without glutamine in autologous
stem cell transplantation for hematologic malignancies.
Bone Marrow Transplantation. 2003; Vol. 31 (Suppl 1):
S219–20.
Pytilik 2002a {published data only}
Pytilik R, Benes P, Gregora E, Pajorkova M, Chocenska
E, Prochazka B, et al.No role for parenteral glutamine
supplementation in autologous stem cell transplant
patients: results of a triple blinded study. Bone Marrow
Transplantation. 2002; Vol. 29 (Suppl2):S20.
Pytilik 2002b {published data only}
Pytilik R, Benes P, Patorkova M, Chocenska E, Gregora E,
Prochazka B, et al.Standardised Parenteral alanyl glutamine
dipeptide supplementation is not beneficial in autologous
transplant patients: a randomised, double blind, placebo
controlled study.. Bone Marrow Transplantation 2002;30
(12):953–61.
Ramsay 1981 {published data only}
Ramsay N. Prevention of graft versus host disease (GVHD)
in bone marrow transplantation (BMT) recipients: A
randomized study. Procedures of the American Association
of Cancer Research. 1981.
Reiffers 1996 {published data only}
Reiffers J. Allogeneic vs autologous stem cell transplantation
vs chemotherapy in patients with acute myeloid leukemia
in first remission: the BGMT 87 study. Leukemia 1996;10
(12):1874–82.
Sax 1992 {published data only}
Sax HC. Clinical and metabolic efficacy of glutamine-
supplemented parenteral nutrition after bone marrow
transplantation. A randomized, double-blind, controlled
study. Journal of Parenteral and Enteral Nutrition 1992;16
(6):589–90.
Schied 2004 {published data only}
Schied C, Hermann K, Kremer G, Holsing A, Heck G,
Fuchs M, et al.Randomized, double blind, controlled study
of glycl-glutamine-dipeptide in the parenteral nutrition
of patients with acute leukaemia undergoing intensive
chemotherapy. Nutrition 2004;20:249–54.
Souba 1993 {published data only}
Souba WW. Total parenteral nutrition with glutamine in
bone marrow transplantation and other clinical applications.
Journal of Parenteral and Enteral Nutrition 1993;17(5):403.
Stern 2000 {published data only}
Jean M Stern, Barbara Bruemmer, Carol M Moinpour,
Keith Sullivan, Polly Lennssen, Saundra Aker. lmpact of a
randomised, controlled trial of liberal versus conservative
hospital discharge criteria on energy, protein and fluid
intake in patients who received marrow transplants. Journal
of the American Dietetic Association 2000;100:1015–22.
Takatsuka 2001 {published data only}
Takatsuka H, Takemoto Y, Iwata N, Suehiro A, Hamano
T, Kanamaru A, et al.Oral Eicosapentaenoic acid for
complications of bone marrow transplantation. Bone
Marrow Transplantation 2001;28(8):769–74.
Ziegler 2001 {published data only}
Thomas R Ziegler. Glutamine Supplementation in Cancer
Patients Receiving Bone Marrow Transplantation and High
Dose Chemotherapy. The Journal of Nutrition September
2001;131(9S):2578S–84S.
Ziegler 2002 {published data only}
Ziegler TR. Glutamine supplementation in bone marrow
transplantation. British Journal of Nutrition 2002;87, Suppl
1:S9–15.
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cytotoxic therapy: an exploratory study on the need for
parenteral nutrition after various treatment approaches
for haematological malignancies. Bone Marrow Transplant
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Kudsk KA. Gut mucosal nutritional support- enteral
nutrition as primary therapy after multiple system trauma.
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10Nutrition support for bone marrow transplant patients (Review)
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Rickard 1980
Rickard KA. Effectiveness of enteral and parenteral nutrition
in the nutritional management of children with Wilm’s
tumour. Clinical Nutrition 1980;33:2622–9.
Weisdorf 1984
Weisdorf S, Hofland C, Harvey LS, Teasley K, Schissel
K, McGlave PB, et al.Total parenteral nutrition in bone
marrow transplantation : A clinical evaluation. Journal of
Paediatric Gastroenterology and Nutrition 1984;3:95–100.∗ Indicates the major publication for the study
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C H A R A C T E R I S T I C S O F S T U D I E S
Characteristics of included studies [ordered by study ID]
Aldamiz 1996
Methods Randomised controlled trial
Method of randomisation is not clear.
Participants 24 recruited
BMT type 6 Allogeneic and 18 Autologous BMT patients.
Disease type not specified
Age mean(+/-SD) years:
Continuous PN = 37(+/-9.3)
Cyclical PN = 35.4(+/- 11.1)
Interventions 12 Continuous PN
12 Cyclical PN
Start criteria: Day +1 after BMT
Stop criteria: not clear.
Outcomes Hospital duration
Change in body weight
Graft versus host disease
Duration of PN
Duration neutropaenia
Notes There were no losses to follow up.
Risk of bias
Bias Authors’ judgement Support for judgement
Allocation concealment (selection bias) Unclear risk B - Unclear
Anderson 1998
Methods Randomised controlled trial.
Method of randomisation is truly random (computer generated random number list.)
Participants 195 recruited
BMT type: 106 Allogeneic/87 Autologous
Disease type: Haem malignancy 106
Haem disorders 8
Solid tumour 62
Inherited disorders 17
Age (yrs) - mean (range)
Oral Glutamine = 29 (1-62)
Oral Placebo = 27 (1-62)
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Anderson 1998 (Continued)
Interventions Randomisation:
98 -Oral mouth rinse glutamine or 1 g/m2, x4/day.
95 - Oral mouth rinse glycine 1g/m2, x4/day
Start criteria: 7 days before BMT
Stop criteria: 28 days after BMT
Outcomes Mucositis
Graft versus host disease
Survival at day 28 and day 100.
Notes Follow up:195 recruited, 2 withdrew
98 - Glutamine group ( 2 did not participate)
95 - Control
Risk of bias
Bias Authors’ judgement Support for judgement
Allocation concealment (selection bias) Low risk A - Adequate
Aquino 2005
Methods Randomised controlled trial.
Method of randomisation was via a random permutation table at a central pharmacy
Participants 120 CHILDREN recruited
BMT type: 106 Allogeneic: 54
Autologous: 66
Disease type: Haem malignancy 64
Solid tumour:48
Haem abnormalities: 10
Age (yrs) - mean
Oral Glutamine =8.9yr
Oral Glycine = 10.5
Interventions Oral glutamine v Oral glycine 2g/m2 (max 4g/day) dissolved in 500 ml solution adminis-
tered twice daily
Outcomes % of doses taken
Hospital days (?units)
Mucositis score
Toxicities
IV narcotic use (days)
PN use (days)
Episodes of bacteraemia
Toxities (including mortality)
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Aquino 2005 (Continued)
Notes The study was described as a double blind randomised controlled trial. Method of ran-
domisation was clear but there was no mention on whether the assessors were blind to the
treatment allocation. There were no apparent losses to follow up
Risk of bias
Bias Authors’ judgement Support for judgement
Allocation concealment (selection bias) Unclear risk B - Unclear
Brown 1998
Methods Randomised controlled trial
Method of randomisation is truly random
Participants 34 recruited
BMT type: 7 Allogeneic/ 27 Autologous
Disease type: 34 Haem malignancy
Age- years, median (range)
Glutamine = 41(19-62)
Control = 32 (16-55)
Interventions Randomisation:
18 PN + Glutamine (50 g glutamine/day)
16 to Standard PN (no glutamine)
Start criteria: day -7 before BMT
Stop criteria: on day discharge.
Outcomes Change in body weight
Graft versus host disease
Survival
Notes Follow up :34 recruited, 8 withdrew.
18- Glutamine group
( four withdrew)
16- Control group ( four withdrew)
Risk of bias
Bias Authors’ judgement Support for judgement
Allocation concealment (selection bias) Low risk A - Adequate
14Nutrition support for bone marrow transplant patients (Review)
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Charuhas 1997
Methods Randomised controlled trial
Method of randomisation is not clear.
Participants 265 BMT (Out patients) recruited
BMT type: 212 Allogeneic/ 53 Autologous
Disease type: 241 Haem malignancy,
2 Haem disorders
12 solid tumour
3 Inherited disorders
Age (range) years:
PN group = 2.7 - 64.2 yrs
IV hydration = 2.1 - 63.1 yrs.
Interventions Randomisation:
128 PN
130 IV Hydration
Start criteria: at discharge
Stop criteria: oral intake >85% energy requirements, for 3 consecutive days
Outcomes Hospital readmission
Time to resume oral intake
Change in body weight
GVHD
Survival to day 150 (post BMT)
Notes
Risk of bias
Bias Authors’ judgement Support for judgement
Allocation concealment (selection bias) Unclear risk B - Unclear
Coghlin Dickson 2000
Methods Randomised controlled trial
Method of randomisation is not clear.
Participants 58 recruited
BMT type: 24 Allogeneic/ 34 Autologous
Disease type: 59 Haem malignancy
Age (range) years:
Glutamine group:17-58 yrs
Control: 21-59 yrs
Interventions Randomisation:
29 Oral Glutamine (10 g x 3 doses/day).
29 Placebo (Sucrose, 10 g x 3/day).
15Nutrition support for bone marrow transplant patients (Review)
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Coghlin Dickson 2000 (Continued)
Outcomes Hospital duration
Mucositis
Duration of PN
Engraftment
Survival at 2 years
Notes There were no losses to follow up.
Risk of bias
Bias Authors’ judgement Support for judgement
Allocation concealment (selection bias) Unclear risk B - Unclear
Cope 1997
Methods Randomised controlled trial.
Method of randomisation is not clear.
Participants 63 recruited
BMT type: not specified
Disease type: not specified
Age - not specified
Interventions Randomisation:
23 EN
40 PN
Start/Stop criteria:not stated.
Outcomes Hospital duration
Mucositis
Change in nutritional status
Notes Loss to follow up is not clear.
Risk of bias
Bias Authors’ judgement Support for judgement
Allocation concealment (selection bias) Unclear risk B - Unclear
16Nutrition support for bone marrow transplant patients (Review)
Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Jebb 1995
Methods Randomised controlled trial.
Method of randomisation is not clear.
Participants 24 recruited
BMT type: 24 Autologous
Disease type: 24 Haem malignancy
Age range not specified.
Interventions Randomisation:
12 Oral mouth rinse glutamine, 4g x 4/d.
12 Oral mouth rinse polycal, 4g x 4/d.
Start criteria: day +1 after BMT until Stop criteria: mucositis resolved or discharge
Outcomes Hospital duration
Mucositis
Duration of PN
Duration of neutropaenia
Notes Follow up: 24 recruited, 8 withdrew.
12- Oral glutamine group ( four withdrew)
12- Control group ( four withdrew)
.
Risk of bias
Bias Authors’ judgement Support for judgement
Allocation concealment (selection bias) Unclear risk B - Unclear
Jimenez 1999
Methods Randomised controlled trial.
Method of randomisation is not clear.
Participants 62 BMT patients.
Interventions Randomisation:
19 - 22.5% BCAA* + 20%LCT
26 - 45% BCAA* + 20%LCT*
17- 45% BCAA*+ 20%MCT*/ LCT*
Outcomes Hospital duration
Duration of Mucositis
Duration of PN
Lipid metabolism
Nutritional assessment parameters.
Notes (Original paper in Spanish)
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Jimenez 1999 (Continued)
Risk of bias
Bias Authors’ judgement Support for judgement
Allocation concealment (selection bias) Unclear risk B - Unclear
Lenssen 1987
Methods Randomised controlled trial.
Method of randomisation is truly random.
Participants 40 recruited.
BMT type: 40 Allogeneic
Disease type: 40 Haem malignancy
Age median(range) years:
23%BCAA*, PN = 28.5 (18-48)
45% BCAA*, PN = 28.5 (18-49)
Interventions Randomisation:
20 - 23%BCAA* (PN)
20 - 45% BCAA*(PN)
Start criteria: pre BMT (day not specified)
Stop criteria: oral protein >10g/day.
Outcomes Graft versus host disease
Notes Follow up: 40 recruited, 21 withdrew.
20 - 23%BCAA* (PN) (9 withdrew.)
20 - 45% BCAA*(PN) (12 withdrew.)
Risk of bias
Bias Authors’ judgement Support for judgement
Allocation concealment (selection bias) Low risk A - Adequate
Lenssen 1998
Methods Randomised controlled trial.
Method of randomisation is not clear.
Participants 512 recruited.
BMT type: 419 Allogeneic/ 93 Autologous Disease type: 512 Haem malignancy
Age mean + (range) years:
Standard PN Lipid group = 35 (0.5-65)
PN+ low dose lipid group = 35 (0.4 -67).
18Nutrition support for bone marrow transplant patients (Review)
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Lenssen 1998 (Continued)
Interventions Randomisation:
253 Standard PN Lipid
259 Low dose PN Lipid
Start criteria: oral energy intake < basal requirements
Stop criteria: oral energy intake >10kcals/kg/day.
Outcomes Graft versus host disease.
Death by day 60 and day 150 post BMT.
Notes Follow up: 512 recruited, 43 withdrew.
253 Standard PN (20 withdrew)
259 Low dose PN Lipid
(23 withdrew)
Risk of bias
Bias Authors’ judgement Support for judgement
Allocation concealment (selection bias) Unclear risk B - Unclear
Lough 1990
Methods Randomised controlled trial.
Method of randomisation is truly random.
Participants 29 recruited.
BMT type: 17 Allogeneic/12 Autologous
Disease type: 29 Haem malignancy
Age range (14-44 yrs)
Interventions Randomisation:
14 PN
15 IV Hydration.
Start criteria: day+1 after BMT until Stop criteria: 15 days after BMT?
Outcomes Change in body weight
Notes Follow up: 29 randomised,
14 PN (4 excluded from analysis).
15 IV (none excluded)
Risk of bias
Bias Authors’ judgement Support for judgement
Allocation concealment (selection bias) Low risk A - Adequate
19Nutrition support for bone marrow transplant patients (Review)
Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
MacBurney 1994
Methods Randomised controlled trial.
Method of randomisation is not clear.
Participants 43 recruited
BMT type: 43 Allogeneic
Disease type: not specified
Age range: not specified
Interventions Randomisation:
22 PN+ Glutamine (0.57 g/kg/day
21 Standard PN (no glutamine)
Start criteria: day+1 after BMT
Stop criteria: oral intake > 50% energy requirements for 3 days
Outcomes Hospital duration
Survival
Notes Small sub report from Ziegler’s 1992 study.
Cost is the main outcome reported.
Risk of bias
Bias Authors’ judgement Support for judgement
Allocation concealment (selection bias) Unclear risk B - Unclear
Malhotra 1996
Methods Randomised controlled trial.
Method of randomisation is not clear.
Participants 45 recruited.
BMT type: not specified
Disease type: not specified
Age range: not specified
Interventions Randomisation:
Elemental diet
Normal ad lib diet.
Start criteria - 72 hours pre high dose therapy.
Stop criteria: not stated.
Outcomes Mucositis
Nausea
Diarrhoea
Sugar absorption tests for gastro-duodenal permeability, small bowel absorption and small
bowel permeability
20Nutrition support for bone marrow transplant patients (Review)
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Malhotra 1996 (Continued)
Notes Abstract report only.
Risk of bias
Bias Authors’ judgement Support for judgement
Allocation concealment (selection bias) Unclear risk B - Unclear
Mulder 1989
Methods Randomised controlled trial.
Method of randomisation is not clear.
Participants 22 recruited.
BMT type: 22 Autologous
Disease type: 22 solid tumour
Age (range) years:
PN group = 28- 54 yrs
EN group = 21- 56 yrs.
Interventions Randomisation:
11 PN
11 PN+EN
Start criteria:day + 4 after BMT
Stop criteria: leukocyte count > 1x 109.
Outcomes Hospital duration
Change in body weight
Survival
Notes There were no losses to follow up.
Risk of bias
Bias Authors’ judgement Support for judgement
Allocation concealment (selection bias) Unclear risk B - Unclear
Muscaritoli 1998
Methods Randomised controlled trial.
Method of randomisation is not clear.
Participants 66 recruited.
BMT type: 66 Allogeneic
Disease type: 66 Haem malignancy
Age mean(range) years:
21Nutrition support for bone marrow transplant patients (Review)
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Muscaritoli 1998 (Continued)
Glucose based PN = 30.5 (15-47)
Lipid based PN = 29.1 (16-44)
Interventions Randomisation:
35 PN Glucose
31 PN Lipid
Start criteria - day +1 after BMT.
Stop criteria - day + 16 after BMT.
Outcomes Hospital duration
Change in body weight.
Graft versus host disease
Survival
Notes Follow up : 66 recruited, 6 withdrew.
35 PN Glucose (4 withdrew)
31 PN Lipid (2 withdrew)
Risk of bias
Bias Authors’ judgement Support for judgement
Allocation concealment (selection bias) Unclear risk B - Unclear
Pytlik 2002
Methods Randomised controlled trial method of randomisation is clear and apart from the hospital
pharmacists all other personnel were blind to the treatment allocation
Participants 40 recruited.
BMT type:
Autologous -40
Disease type: Haem malignancy -32
Solid tumour - 4
Other inherited conditions -4
Age range (mean +/-sd):
Intervention: (PN and Glutamine)
49 +/- 12
Control: Placebo
42+/-14
Interventions Randomisation:
PN + glutamine - n=21
PN + placebo - n =19
Start criteria: administered from day +1 to day +14 or to discharge
22Nutrition support for bone marrow transplant patients (Review)
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Pytlik 2002 (Continued)
Outcomes Mean days of Diarrhoea (>3 stools per day)
Mean oral energy intake
Mean days in hospital post transplantation
Mean days with severe mucositis
Days of PN
Notes For most of the outcomes it did not appear that there was loss to follow up
Risk of bias
Bias Authors’ judgement Support for judgement
Allocation concealment (selection bias) Low risk A - Adequate
Roberts 2003a
Methods Randomised controlled trial.
Method of randomisation is unclear as is the level of allocation concealment
Participants 55 recruited:
BMT type: Autologous -55
Disease type: Solid tumours (Breast cancer):55
Mean Age:
PN group:41.6 yrs
Oral diet group:45.6
Interventions Randomisation:
PN:27
Oral diet:28
(also given IV fluids)
PN started day -1 were also allowed ad lib oral diet.
Outcomes Nutritional status including:
% decrease in body weight
Nos with +ve blood cultures
No. days on antibiotics
Liver function
Change in mood disturbance
% probability of survival at 2 and 5 years.
Notes
Risk of bias
Bias Authors’ judgement Support for judgement
Allocation concealment (selection bias) Unclear risk B - Unclear
23Nutrition support for bone marrow transplant patients (Review)
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Santos 2001
Methods Randomised cross over controlled trial.
Method of randomisation is truly random although the extent of blinding of the participants
and the investigators is unclear
Participants 10 recruited:
BMT type: 10 allogeneic transplant patients
Disease type: all had haematological malignancies
Mean age: 36.7 years (sd 12.0).
Interventions Randomisation:
Group 1: PN with lipid for 4 days and then PN without lipids for 4 days.
Intervention group 2: PN without lipids for 4 days and then PN with lipids for 4 days.
The composition of the PN lipid solution was given as 0.8 g/kg/d of 50:50 mixture of
medium and long chain triglycerides
Outcomes Levels of cyclosporin in blood samples.
Notes The authors reported that cyclosporin A pharmokinetics were not influenced by varying
types of lipid enriched PN admixtures
Risk of bias
Bias Authors’ judgement Support for judgement
Allocation concealment (selection bias) Unclear risk B - Unclear
Scheltinga 1991
Methods Randomised controlled trial.
Method of randomisation is not clear.
Participants 20 recruited.
BMT type: 20 Allogeneic
Disease type: 20 Haem malignancy
Age( years)- mean(SEM)
PN + Glutamine - 36+/-3
Standard PN - 33+/-3
Interventions Randomisation:
10 PN+Glutamine (0.57g/kg/day)
10 Standard PN (no glutamine)
Start criteria: day+1 after BMT
Stop criteria: oral intake > 50% energy requirements for 3 days
Outcomes Hospital duration
Change in body weight.
Duration of PN
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Scheltinga 1991 (Continued)
Notes There were no losses to follow up.
Small sub report from Ziegler’s 1992 study.
Risk of bias
Bias Authors’ judgement Support for judgement
Allocation concealment (selection bias) Unclear risk B - Unclear
Schloerb 1993
Methods Randomised controlled trial.
Method of randomisation is truly random.
Participants 29 recruited.
BMT type: 13 Allogeneic/ 16 Autologous
Disease type: 26 Haem malignancy
3 Solid tumour
Age (years) - mean (range)
PN + Glutamine 35.6(19-55)
Standard PN - 37.6 (19-55)
Interventions Randomisation:
16 PN+ Glutamine (2830 mg glutamine/100 ml)
13 Standard PN (no glutamine)
Start criteria - unclear
Stop criteria - oral intake >50% energy requirements.
Outcomes Hospital duration
Mucositis
Change in body weight.
Duration of PN
Graft versus host disease
Neutropaenia
Positive blood cultures
Notes There were no losses to follow up.
Risk of bias
Bias Authors’ judgement Support for judgement
Allocation concealment (selection bias) Low risk A - Adequate
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Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Schloerb 1999
Methods Randomised controlled trial.
Method of randomisation is truly random.
Participants 66 recruited.
BMT type:19 Allogeneic/ 47 Autologous Disease type: 43 Haem malignancy
23 Solid tumour
Age: all > 17 yrs.
Interventions Randomisation:
35 Oral Glutamine,10g x 3 /day.
33 Oral/PN Glycine, 10g x 3/day.
Start criteria: unclear.
Stop criteria: oral intake >50% energy requirement.
Outcomes Hospital duration
Mucositis
Change in body weight.
Survival
Duration of PN
Notes There were no losses to follow up.
Risk of bias
Bias Authors’ judgement Support for judgement
Allocation concealment (selection bias) Low risk A - Adequate
Szeluga 1987
Methods Randomised controlled trial.
Method of randomisation is not clear.
Participants 65 recruited. 61 participated.
BMT type: 46 Allogeneic/ 15 Autologous
Disease type: 45 Haem malignancy
16 other miscellany of disorders.
Age (years)
PN = 21 > 19 yrs, 10 < 19 yrs.
EN group = 21 > 19 yrs, 9 < 19 yrs.
Interventions Randomisation:
31PN
30 EN
(4 withdrew)
Start criteria: day before BMT
Stop criteria: 28 days after BMT
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Szeluga 1987 (Continued)
Outcomes Hospital duration
Duration of PN
Change in body weight.
Neutropaenia
Graft versus host disease
Survival
Notes 65 recruited.
61 participated, 4 withdrew. 57 could be evaluated at day 28.
27 PN group (4 treatment failures).
30 EN group. (7 received PN).
Although 7 failed enteral feeds and received PN their outcomes were included in the EN
group analysis.
However 2 from the PN group were crossed at some stage into the EN group and were
included in the EN group analysis . Consequently numbers for each outcome presented
are unclear and none can be used
Risk of bias
Bias Authors’ judgement Support for judgement
Allocation concealment (selection bias) Unclear risk B - Unclear
Takatsuka 2002
Methods Randomised controlled trial.
Method of randomisation is not clear.
Participants 17 recruited.
BMT type: Allogeneic - 17
Disease type - haematological malignancy - 17
Age: < 17yrs - 1
>/= 17yrs - 16
Interventions Randomisation:
8 - eicosapentaenoic acid(EPA) from day -21 to day 180 post BMT
9 - received nil
Outcomes Numbers developing GVHD - graft versus host disease
Notes
Risk of bias
Bias Authors’ judgement Support for judgement
Allocation concealment (selection bias) Unclear risk B - Unclear
27Nutrition support for bone marrow transplant patients (Review)
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Weisdorf 1987
Methods Randomised controlled trial.
Method of randomisation is not clear.
Participants 137 recruited.
BMT type:104 Allogeneic/ 32 Autologous
Disease type:118 Haem malignancy
8 Solid tumour
3 Inherited disorder
5 Haem abnormalities
1 other malignancy
2 unaccounted
Age - years, mean (+/-SD) for
PN group = 20 (+/- 12.9)
IV hydration = 18.3 (+/- 12.9)
Interventions Randomisation:
71 PN
66 IV Hydration.
Start criteria: 7 days before BMT.
Stop criteria: 4 weeks post BMT.
Outcomes Hospital duration
Change in body weight.
Survival
Notes Difficulty extracting data from paper.
There were no apparent losses to follow up.
Risk of bias
Bias Authors’ judgement Support for judgement
Allocation concealment (selection bias) Unclear risk B - Unclear
Young 1993
Methods Randomised controlled trial.
Method of randomisation is not clear.
Participants 23 recruited.
BMT type: 23 Allogeneic
Disease type: 23 Haem malignancy
Age (yrs) (mean (range):
PN + Glutamine = 36 (20-49)
Standard PN = 30 (22-44)
Interventions Randomisation:
13 PN + Glutamine (0.57g glutamine/kg/day)
10 Standard PN
28Nutrition support for bone marrow transplant patients (Review)
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Young 1993 (Continued)
Start criteria : Day + 1 after BMT.
Stop criteria : oral intake >50% energy requirements.
Outcomes Hospital duration
Duration of PN
Notes There were no losses to follow up.
Small report from
Ziegler’s 1992 study.
Main outcome reported is mood.
Risk of bias
Bias Authors’ judgement Support for judgement
Allocation concealment (selection bias) Low risk A - Adequate
Young 1997
Methods Randomised controlled trial.
Method of randomisation is not clear.
Participants 20 recruited
BMT type:20 Allogeneic
Disease type: not specified
Age: not specified
Allogeneic BMT patients.
Age - not specified
Interventions Randomisation:
10 PN
10 EN
Start criteria: weight loss >10% nutritional requirements inadequate.
Stop criteria:not stated.
Outcomes Duration of feeding (PN/EN
Change in body weight.
Notes Follow up: 20 recruited, 5 withdrew.
10 PN
10 EN ( 5 withdrew)
Abstract version only.
Risk of bias
Bias Authors’ judgement Support for judgement
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Young 1997 (Continued)
Allocation concealment (selection bias) Unclear risk B - Unclear
Ziegler 1992
Methods Randomised controlled trial.
Method of randomisation is not clear.
Participants 45 recruited.
BMT type: 45 Allogeneic
Disease type: 45 Haem malignancy
Age (years) - mean (range)
PN + Glutamine - 32.1(20-48)
Standard PN - 35.5(20-49)
Interventions Randomisation:
24 PN+ Glutamine (0.57g/kg/day)
21 Standard PN ( no glutamine).
Start criteria: day+1 after BMT
Stop criteria: oral intake > 50% energy requirements for 3 days
Outcomes Hospital duration
Duration of PN
Mucositis
Neutropaenia
Graft versus host disease
Positive blood cultures
Survival
Notes Follow up: 45 recruited.
24 PN + Glutamine - 2 were not followed up for hospital duration but were for all other
outcomes reported.
21 Standard PN - (1 withdrew)
Note a number of studies are sub reports of this main study and they will not be included
in the analysis
Risk of bias
Bias Authors’ judgement Support for judgement
Allocation concealment (selection bias) Low risk A - Adequate
30Nutrition support for bone marrow transplant patients (Review)
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Ziegler 1998
Methods Randomised controlled trial.
Method of randomisation is not clear.
Participants 20 recruited.
BMT type: 20 Allogeneic
Disease type: 20 Haem malignancy
Age (years) - mean (+/- SE)
PN + Glutamine - 36 (+/- 3
Standard PN - 35 (+/-3)
Interventions Randomisation:
9 PN+ Glutamine (0.57 g/kg/day)
11 Standard PN ( no glutamine).
Start criteria - day+1 after BMT
Stop criteria - not stated
Outcomes Duration of PN
Neutropaenia
Clinical infection
Notes There were no losses to follow up.
Small report from Ziegler’s main 1992 study.
Main outcome reported effect on circulating lymphocytes.
Risk of bias
Bias Authors’ judgement Support for judgement
Allocation concealment (selection bias) Unclear risk B - Unclear
Characteristics of excluded studies [ordered by study ID]
Study Reason for exclusion
Clemens 1997 This is not a randomised controlled trial.
Cohen 1996 This is not a report of a randomised controlled trial but single case report
Duggan 2004 These patients were not bone marrow transplant patients they were infants with gastrointestinal disease
Ford 1992 The study does not include bone marrow transplant patients.
Hopman 2003 This study compared enteral nutrition versus parenteral nutrition however the investigators combined data of
patients who were randomised into the study with patients who were not randomised into the study. Conse-
quently the data from the randomised patients was merged with the data from the non randomised patients
preventing the data of the randomised patients to be evaluated
31Nutrition support for bone marrow transplant patients (Review)
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(Continued)
Klein 1994 This is not a report of a randomised controlled trial.
Lipman 1991a This is not a report of a randomised controlled trial but a report of a review of clinical trials of nutrition support
in Cancer patients
Mercadante 1998a This is not a report of a randomised controlled trial but a report on the benefits of enteral nutrition versus
parenteral nutrition for oncology patients
Mobrahan 1992 This is not a report of a randomised controlled trial but instead a report on the potential benefits of glutamine
for Bone Marrow Transplant patients
Piccirillo 2002 The data was presented in abstract form however it was not possible to adequately evaluate this study report
Piccirillo 2004 The data was presented in abstract form and was not evaluable
Poznarova 2003 The data was presented in abstract form and was not evaluable
Pytilik 2002a The data was presented in abstract form and was not evaluable
Pytilik 2002b The data was presented in abstract form and was not evaluable
Ramsay 1981 This randomised controlled trial did not use any form or type of nutrition support as its intervention
Reiffers 1996 This randomised controlled trial did not use any form or type of nutrition support as its intervention
Sax 1992 This is not a report of a randomised controlled trial but a comment report of a randomised controlled trial
(Ziegler 1992) that compared glutamine supplemented PN with standard PN
Schied 2004 This randomised controlled study which compared standard PN with PN and glutamine was conducted on
patients receiving intensive chemotherapy but they did not undergo bone marrow transplantation within this
study. This study is excluded because it did not meet the population inclusion criteria
Souba 1993 This is not a report of a randomised controlled trial but a comment report of other randomised controlled trials
that have compared glutamine supplemented PN with standard PN
Stern 2000 The intervention was related to early versus delayed discharge home and did not meet the inclusion criteria
Takatsuka 2001 This study is excluded since data from the same study published a year later is being included within this review
Ziegler 2001 This was not a randomised controlled trial but a review paper
Ziegler 2002 This was not a randomised controlled trial but a review paper
32Nutrition support for bone marrow transplant patients (Review)
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D A T A A N D A N A L Y S E S
Comparison 1. Oral glutamine versus oral placebo studies
Outcome or subgroup titleNo. of
studies
No. of
participants Statistical method Effect size
1 Mean duration (+/-SD) of time
in hospital (e.g. admission to
discharge or from day ’0’ to
discharge).
5 453 Mean Difference (IV, Fixed, 95% CI) -2.39 [-6.11, 1.34]
2 Mean(+/-SD) number of days
patients had some degree of
mucositis from start to end of
study.
5 335 Mean Difference (IV, Fixed, 95% CI) 0.0 [0.0, 0.0]
3 Number of patients who
developed line infections from
start to end of study.
5 335 Peto Odds Ratio (Peto, Fixed, 95% CI) 0.0 [0.0, 0.0]
4 Difference in mean % change in
body weight from start to end
of the study between the trial
groups.
5 327 Mean Difference (IV, Fixed, 95% CI) 5.73 [-7.09, 18.55]
5 Mean duration (+/-SD) that
nutritional intervention is
given as PN.
6 455 Mean Difference (IV, Fixed, 95% CI) 1.00 [-4.42, 2.43]
6 Number of patients who
developed > grade 2 graft versus
host disease (GVHD).
5 335 Peto Odds Ratio (Peto, Fixed, 95% CI) 0.0 [0.0, 0.0]
7 Number of days(+/-SD) to
achieve normal neutrophil level
(>0.5 X 10/9/l) after day 0 of
BMT.
5 335 Mean Difference (IV, Fixed, 95% CI) 6.82 [1.67, 11.98]
8 Actual numbers of patients who
have completed the study and
survived to the 100th day post
BMT.
5 453 Peto Odds Ratio (Peto, Fixed, 95% CI) 1.51 [0.88, 2.60]
9 Actual number of patients who
have completed the study and
survived beyond day 100 post
BMT.
5 453 Peto Odds Ratio (Peto, Fixed, 95% CI) 0.0 [0.0, 0.0]
10 Number with positive blood
cultures
1 66 Peto Odds Ratio (Peto, Fixed, 95% CI) 1.18 [0.39, 3.62]
33Nutrition support for bone marrow transplant patients (Review)
Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Comparison 2. PN + glutamine versus standard PN
Outcome or subgroup titleNo. of
studies
No. of
participants Statistical method Effect size
1 Mean duration(+/-SD) of time
in hospital (e.g. admission to
discharge or from day 0 to
discharge home).
4 143 Mean Difference (IV, Fixed, 95% CI) 0.22 [-1.29, 1.72]
2 Mean(+/-SD) cumulative
mucositis score
4 147 Mean Difference (IV, Fixed, 95% CI) -0.02 [-0.48, 0.45]
3 Number of patients who
developed line infections from
start to end of study.
4 110 Peto Odds Ratio (Peto, Fixed, 95% CI) 0.0 [0.0, 0.0]
4 Difference in mean % change in
body weight from start to end
of the study between the trial
groups.
4 107 Mean Difference (IV, Fixed, 95% CI) -0.34 [-1.40, 0.72]
5 Mean duration (+/-SD) that
nutritional intervention is
given.
4 147 Mean Difference (IV, Fixed, 95% CI) 0.36 [-1.63, 2.35]
6 Number of patients who
developed >/=grade 2 graft
versus host disease (GVHD).
4 109 Peto Odds Ratio (Peto, Fixed, 95% CI) 0.57 [0.18, 1.83]
7 Number of days(+/-SD) to
achieve normal neutrophil level
(>0.5 X 10/9/l) after day 0 of
BMT.
4 106 Mean Difference (IV, Fixed, 95% CI) 0.57 [-1.63, 2.76]
8 Actual numbers of patients who
have completed the study and
survived to the 100th day post
BMT.
4 109 Peto Odds Ratio (Peto, Fixed, 95% CI) 0.69 [0.16, 2.97]
9 Number of patients with positive
blood cultures
4 147 Peto Odds Ratio (Peto, Fixed, 95% CI) 0.46 [0.20, 1.04]
Comparison 3. PN vs IV hydration
Outcome or subgroup titleNo. of
studies
No. of
participants Statistical method Effect size
1 Mean duration (+/-SD) of time
in hospital (e.g. from discharge
admission to discharge or day 0
to discharge).
3 221 Mean Difference (IV, Fixed, 95% CI) 3.30 [-0.38, 6.98]
2 Mean(+/-SD) number of days
patients had some degree of
mucositis from start to end of
study.
3 221 Mean Difference (IV, Fixed, 95% CI) 0.0 [0.0, 0.0]
34Nutrition support for bone marrow transplant patients (Review)
Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
3 Number of patients who
developed line infections from
start to end of study.
3 217 Peto Odds Ratio (Peto, Fixed, 95% CI) 21.23 [4.15, 108.73]
4 Difference in mean % change in
body weight from start to end
of the study between the trial
groups.
3 217 Mean Difference (IV, Fixed, 95% CI) 2.81 [1.34, 4.29]
5 Mean duration (+/-SD) that
nutritional intervention is
given.
3 221 Mean Difference (IV, Fixed, 95% CI) 12.2 [8.66, 15.74]
6 Number of patients who
developed > grade 2 graft versus
host disease (GVHD).
3 221 Peto Odds Ratio (Peto, Fixed, 95% CI) 0.0 [0.0, 0.0]
7 Number of days(+/-SD) to
achieve normal neutrophil level
(>0.5 X 10/9/l) after day 0 of
BMT.
3 221 Mean Difference (IV, Fixed, 95% CI) 0.0 [0.0, 0.0]
8 Actual numbers of patients who
have completed the study and
survived to the 100th day post
BMT.
3 221 Peto Odds Ratio (Peto, Fixed, 95% CI) 0.0 [0.0, 0.0]
9 Actual number of patients who
survived to day 200 post BMT.
3 221 Peto Odds Ratio (Peto, Fixed, 95% CI) 2.10 [0.48, 9.18]
10 Mean % change in albumin 3 217 Mean Difference (IV, Fixed, 95% CI) -3.72 [-5.96, -1.49]
Comparison 4. PN vs enteral feeding studies
Outcome or subgroup titleNo. of
studies
No. of
participants Statistical method Effect size
1 Mean duration (+/-SD) of
time in hospital (e.g. from
admission to discharge or day 0
to discharge).
3 144 Mean Difference (IV, Fixed, 95% CI) 0.0 [0.0, 0.0]
2 Mean(+/-SD) number of days
patients had some degree of
mucositis from start to end of
study.
3 144 Mean Difference (IV, Fixed, 95% CI) 0.0 [0.0, 0.0]
3 Number of patients who
developed line infections from
start to end of study.
3 144 Peto Odds Ratio (Peto, Fixed, 95% CI) 0.0 [0.0, 0.0]
4 Difference in mean % change in
body weight from start to end
of the study between the trial
groups.
3 144 Mean Difference (IV, Fixed, 95% CI) 0.0 [0.0, 0.0]
5 Mean duration (+/-SD) that
nutritional intervention is
given.
3 144 Mean Difference (IV, Fixed, 95% CI) 0.0 [0.0, 0.0]
35Nutrition support for bone marrow transplant patients (Review)
Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
6 Number of patients who
developed > grade 2 graft versus
host disease (GVHD).
3 144 Peto Odds Ratio (Peto, Fixed, 95% CI) 0.0 [0.0, 0.0]
7 Number of days(+/-SD) to
achieve normal neutrophil level
(>0.5 X 10/9/l) after day 0 of
BMT.
3 144 Mean Difference (IV, Fixed, 95% CI) 0.0 [0.0, 0.0]
8 Actual numbers of patients who
have completed the study and
survived to the 100th day post
BMT.
3 144 Peto Odds Ratio (Peto, Fixed, 95% CI) 0.0 [0.0, 0.0]
9 Actual number of patients who
have completed the study and
survived beyond day 200 post
BMT.
3 144 Peto Odds Ratio (Peto, Fixed, 95% CI) 0.0 [0.0, 0.0]
Comparison 5. Oral eicosapentaenoic acid supplementation versus nil
Outcome or subgroup titleNo. of
studies
No. of
participants Statistical method Effect size
1 Numbers not developing graft
versus host disease
1 17 Odds Ratio (M-H, Fixed, 95% CI) 12.09 [0.52, 280.40]
36Nutrition support for bone marrow transplant patients (Review)
Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Analysis 1.1. Comparison 1 Oral glutamine versus oral placebo studies, Outcome 1 Mean duration (+/-SD)
of time in hospital (e.g. admission to discharge or from day ’0’ to discharge)..
Review: Nutrition support for bone marrow transplant patients
Comparison: 1 Oral glutamine versus oral placebo studies
Outcome: 1 Mean duration (+/-SD) of time in hospital (e.g. admission to discharge or from day ’0’ to discharge).
Study or subgroup Oral Glutamine PlaceboMean
DifferenceMean
Difference
N Mean(SD) N Mean(SD) IV,Fixed,95% CI IV,Fixed,95% CI
Anderson 1998 98 0 (0) 95 0 (0) 0.0 [ 0.0, 0.0 ]
Aquino 2005 57 0 (0) 63 0 (0) 0.0 [ 0.0, 0.0 ]
Coghlin Dickson 2000 29 0 (0) 29 0 (0) 0.0 [ 0.0, 0.0 ]
Jebb 1995 8 25.6 (2.2) 8 28.3 (5.5) -2.70 [ -6.80, 1.40 ]
Schloerb 1999 35 30.71 (15.19) 31 31.65 (20.69) -0.94 [ -9.79, 7.91 ]
Total (95% CI) 227 226 -2.39 [ -6.11, 1.34 ]
Heterogeneity: Chi2 = 0.12, df = 1 (P = 0.72); I2 =0.0%
Test for overall effect: Z = 1.26 (P = 0.21)
Test for subgroup differences: Not applicable
-10 -5 0 5 10
Oral Glutamine Placebo
37Nutrition support for bone marrow transplant patients (Review)
Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Analysis 1.2. Comparison 1 Oral glutamine versus oral placebo studies, Outcome 2 Mean(+/-SD) number of
days patients had some degree of mucositis from start to end of study..
Review: Nutrition support for bone marrow transplant patients
Comparison: 1 Oral glutamine versus oral placebo studies
Outcome: 2 Mean(+/-SD) number of days patients had some degree of mucositis from start to end of study.
Study or subgroup Oral glutamine PlaceboMean
DifferenceMean
Difference
N Mean(SD) N Mean(SD) IV,Fixed,95% CI IV,Fixed,95% CI
Anderson 1998 98 0 (0) 95 0 (0) 0.0 [ 0.0, 0.0 ]
Aquino 2005 1 0 (0) 1 0 (0) 0.0 [ 0.0, 0.0 ]
Coghlin Dickson 2000 29 0 (0) 29 0 (0) 0.0 [ 0.0, 0.0 ]
Jebb 1995 8 0 (0) 8 0 (0) 0.0 [ 0.0, 0.0 ]
Schloerb 1999 35 0 (0) 31 0 (0) 0.0 [ 0.0, 0.0 ]
Total (95% CI) 171 164 0.0 [ 0.0, 0.0 ]
Heterogeneity: Chi2 = 0.0, df = 0 (P<0.00001); I2 =0.0%
Test for overall effect: Z = 0.0 (P < 0.00001)
Test for subgroup differences: Not applicable
-10 -5 0 5 10
Oral Glutamine Placebo
38Nutrition support for bone marrow transplant patients (Review)
Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Analysis 1.3. Comparison 1 Oral glutamine versus oral placebo studies, Outcome 3 Number of patients
who developed line infections from start to end of study..
Review: Nutrition support for bone marrow transplant patients
Comparison: 1 Oral glutamine versus oral placebo studies
Outcome: 3 Number of patients who developed line infections from start to end of study.
Study or subgroup Oral Glutamine PlaceboPeto
Odds RatioPeto
Odds Ratio
n/N n/N Peto,Fixed,95% CI Peto,Fixed,95% CI
Anderson 1998 0/98 0/95 0.0 [ 0.0, 0.0 ]
Aquino 2005 0/1 0/1 0.0 [ 0.0, 0.0 ]
Coghlin Dickson 2000 0/29 0/29 0.0 [ 0.0, 0.0 ]
Jebb 1995 0/8 0/8 0.0 [ 0.0, 0.0 ]
Schloerb 1999 0/35 0/31 0.0 [ 0.0, 0.0 ]
Total (95% CI) 171 164 0.0 [ 0.0, 0.0 ]
Total events: 0 (Oral Glutamine), 0 (Placebo)
Heterogeneity: Chi2 = 0.0, df = 0 (P<0.00001); I2 =0.0%
Test for overall effect: Z = 0.0 (P < 0.00001)
Test for subgroup differences: Not applicable
0.1 0.2 0.5 1 2 5 10
Oral Glutamine Placebo
39Nutrition support for bone marrow transplant patients (Review)
Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Analysis 1.4. Comparison 1 Oral glutamine versus oral placebo studies, Outcome 4 Difference in mean %
change in body weight from start to end of the study between the trial groups..
Review: Nutrition support for bone marrow transplant patients
Comparison: 1 Oral glutamine versus oral placebo studies
Outcome: 4 Difference in mean % change in body weight from start to end of the study between the trial groups.
Study or subgroup Oral Glutamine PlaceboMean
DifferenceMean
Difference
N Mean(SD) N Mean(SD) IV,Fixed,95% CI IV,Fixed,95% CI
Anderson 1998 98 0 (0) 95 0 (0) 0.0 [ 0.0, 0.0 ]
Aquino 2005 1 0 (0) 1 0 (0) 0.0 [ 0.0, 0.0 ]
Coghlin Dickson 2000 29 0 (0) 29 0 (0) 0.0 [ 0.0, 0.0 ]
Jebb 1995 8 0 (0) 8 0 (0) 0.0 [ 0.0, 0.0 ]
Schloerb 1999 32 0.06 (27.1) 26 -5.67 (22.7) 5.73 [ -7.09, 18.55 ]
Total (95% CI) 168 159 5.73 [ -7.09, 18.55 ]
Heterogeneity: Chi2 = 0.0, df = 0 (P = 1.00); I2 =0.0%
Test for overall effect: Z = 0.88 (P = 0.38)
Test for subgroup differences: Not applicable
-10 -5 0 5 10
Placebo Oral Glutamine
40Nutrition support for bone marrow transplant patients (Review)
Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Analysis 1.5. Comparison 1 Oral glutamine versus oral placebo studies, Outcome 5 Mean duration (+/-SD)
that nutritional intervention is given as PN..
Review: Nutrition support for bone marrow transplant patients
Comparison: 1 Oral glutamine versus oral placebo studies
Outcome: 5 Mean duration (+/-SD) that nutritional intervention is given as PN.
Study or subgroup Oral Glutamine PlaceboMean
DifferenceMean
Difference
N Mean(SD) N Mean(SD) IV,Fixed,95% CI IV,Fixed,95% CI
Aldamiz 1996 1 0 (0) 1 0 (0) 0.0 [ 0.0, 0.0 ]
Anderson 1998 98 0 (0) 95 0 (0) 0.0 [ 0.0, 0.0 ]
Aquino 2005 57 0 (0) 63 0 (0) 0.0 [ 0.0, 0.0 ]
Coghlin Dickson 2000 29 0 (0) 29 0 (0) 0.0 [ 0.0, 0.0 ]
Jebb 1995 8 11.3 (5) 8 6.6 (4.2) 4.70 [ 0.18, 9.22 ]
Schloerb 1999 35 8.89 (5.06) 31 17.55 (14.13) -8.66 [ -13.91, -3.41 ]
Total (95% CI) 228 227 -1.00 [ -4.42, 2.43 ]
Heterogeneity: Chi2 = 14.28, df = 1 (P = 0.00016); I2 =93%
Test for overall effect: Z = 0.57 (P = 0.57)
Test for subgroup differences: Not applicable
-10 -5 0 5 10
Oral Glutamine Placebo
41Nutrition support for bone marrow transplant patients (Review)
Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Analysis 1.6. Comparison 1 Oral glutamine versus oral placebo studies, Outcome 6 Number of patients
who developed > grade 2 graft versus host disease (GVHD)..
Review: Nutrition support for bone marrow transplant patients
Comparison: 1 Oral glutamine versus oral placebo studies
Outcome: 6 Number of patients who developed > grade 2 graft versus host disease (GVHD).
Study or subgroup Oral Glutamine PlaceboPeto
Odds RatioPeto
Odds Ratio
n/N n/N Peto,Fixed,95% CI Peto,Fixed,95% CI
Anderson 1998 0/98 0/95 0.0 [ 0.0, 0.0 ]
Aquino 2005 0/1 0/1 0.0 [ 0.0, 0.0 ]
Coghlin Dickson 2000 0/29 0/29 0.0 [ 0.0, 0.0 ]
Jebb 1995 0/8 0/8 0.0 [ 0.0, 0.0 ]
Schloerb 1999 0/35 0/31 0.0 [ 0.0, 0.0 ]
Total (95% CI) 171 164 0.0 [ 0.0, 0.0 ]
Total events: 0 (Oral Glutamine), 0 (Placebo)
Heterogeneity: Chi2 = 0.0, df = 0 (P<0.00001); I2 =0.0%
Test for overall effect: Z = 0.0 (P < 0.00001)
Test for subgroup differences: Not applicable
0.1 0.2 0.5 1 2 5 10
Oral Glutamine Placebo
42Nutrition support for bone marrow transplant patients (Review)
Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Analysis 1.7. Comparison 1 Oral glutamine versus oral placebo studies, Outcome 7 Number of days(+/-SD)
to achieve normal neutrophil level (>0.5 X 10/9/l) after day 0 of BMT..
Review: Nutrition support for bone marrow transplant patients
Comparison: 1 Oral glutamine versus oral placebo studies
Outcome: 7 Number of days(+/-SD) to achieve normal neutrophil level (>0.5 X 10/9/l) after day 0 of BMT.
Study or subgroup Oral Glutamine PlaceboMean
DifferenceMean
Difference
N Mean(SD) N Mean(SD) IV,Fixed,95% CI IV,Fixed,95% CI
Anderson 1998 98 0 (0) 95 0 (0) 0.0 [ 0.0, 0.0 ]
Aquino 2005 1 0 (0) 1 0 (0) 0.0 [ 0.0, 0.0 ]
Coghlin Dickson 2000 29 0 (0) 29 0 (0) 0.0 [ 0.0, 0.0 ]
Jebb 1995 8 28.4 (11.5) 8 25.4 (11.7) 3.00 [ -8.37, 14.37 ]
Schloerb 1999 35 19.26 (16.3) 31 11.45 (5.88) 7.81 [ 2.03, 13.59 ]
Total (95% CI) 171 164 6.82 [ 1.67, 11.98 ]
Heterogeneity: Chi2 = 0.55, df = 1 (P = 0.46); I2 =0.0%
Test for overall effect: Z = 2.59 (P = 0.0095)
Test for subgroup differences: Not applicable
-10 -5 0 5 10
Oral Glutamine Placebo
43Nutrition support for bone marrow transplant patients (Review)
Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Analysis 1.8. Comparison 1 Oral glutamine versus oral placebo studies, Outcome 8 Actual numbers of
patients who have completed the study and survived to the 100th day post BMT..
Review: Nutrition support for bone marrow transplant patients
Comparison: 1 Oral glutamine versus oral placebo studies
Outcome: 8 Actual numbers of patients who have completed the study and survived to the 100th day post BMT.
Study or subgroup Oral Glutamine PlaceboPeto
Odds RatioPeto
Odds Ratio
n/N n/N Peto,Fixed,95% CI Peto,Fixed,95% CI
Anderson 1998 86/98 77/95 1.66 [ 0.76, 3.61 ]
Aquino 2005 51/57 57/63 0.90 [ 0.27, 2.94 ]
Coghlin Dickson 2000 0/29 0/29 0.0 [ 0.0, 0.0 ]
Jebb 1995 0/8 0/8 0.0 [ 0.0, 0.0 ]
Schloerb 1999 19/35 12/31 1.85 [ 0.71, 4.84 ]
Total (95% CI) 227 226 1.51 [ 0.88, 2.60 ]
Total events: 156 (Oral Glutamine), 146 (Placebo)
Heterogeneity: Chi2 = 0.97, df = 2 (P = 0.61); I2 =0.0%
Test for overall effect: Z = 1.51 (P = 0.13)
Test for subgroup differences: Not applicable
0.1 0.2 0.5 1 2 5 10
Placebo Oral Glutamine
44Nutrition support for bone marrow transplant patients (Review)
Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Analysis 1.9. Comparison 1 Oral glutamine versus oral placebo studies, Outcome 9 Actual number of
patients who have completed the study and survived beyond day 100 post BMT..
Review: Nutrition support for bone marrow transplant patients
Comparison: 1 Oral glutamine versus oral placebo studies
Outcome: 9 Actual number of patients who have completed the study and survived beyond day 100 post BMT.
Study or subgroup Oral Glutamine PlaceboPeto
Odds RatioPeto
Odds Ratio
n/N n/N Peto,Fixed,95% CI Peto,Fixed,95% CI
Anderson 1998 0/98 0/95 0.0 [ 0.0, 0.0 ]
Aquino 2005 0/57 0/63 0.0 [ 0.0, 0.0 ]
Coghlin Dickson 2000 0/29 0/29 0.0 [ 0.0, 0.0 ]
Jebb 1995 0/8 0/8 0.0 [ 0.0, 0.0 ]
Schloerb 1999 0/35 0/31 0.0 [ 0.0, 0.0 ]
Total (95% CI) 227 226 0.0 [ 0.0, 0.0 ]
Total events: 0 (Oral Glutamine), 0 (Placebo)
Heterogeneity: Chi2 = 0.0, df = 0 (P<0.00001); I2 =0.0%
Test for overall effect: Z = 0.0 (P < 0.00001)
Test for subgroup differences: Not applicable
0.1 0.2 0.5 1 2 5 10
Oral Glutamine Placebo
45Nutrition support for bone marrow transplant patients (Review)
Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Analysis 1.10. Comparison 1 Oral glutamine versus oral placebo studies, Outcome 10 Number with
positive blood cultures.
Review: Nutrition support for bone marrow transplant patients
Comparison: 1 Oral glutamine versus oral placebo studies
Outcome: 10 Number with positive blood cultures
Study or subgroup Treatment ControlPeto
Odds Ratio WeightPeto
Odds Ratio
n/N n/N Peto,Fixed,95% CI Peto,Fixed,95% CI
Schloerb 1999 9/35 7/31 100.0 % 1.18 [ 0.39, 3.62 ]
Total (95% CI) 35 31 100.0 % 1.18 [ 0.39, 3.62 ]
Total events: 9 (Treatment), 7 (Control)
Heterogeneity: not applicable
Test for overall effect: Z = 0.29 (P = 0.77)
Test for subgroup differences: Not applicable
0.1 0.2 0.5 1 2 5 10
Favours treatment Favours control
Analysis 2.1. Comparison 2 PN + glutamine versus standard PN, Outcome 1 Mean duration(+/-SD) of time
in hospital (e.g. admission to discharge or from day 0 to discharge home)..
Review: Nutrition support for bone marrow transplant patients
Comparison: 2 PN + glutamine versus standard PN
Outcome: 1 Mean duration(+/-SD) of time in hospital (e.g. admission to discharge or from day 0 to discharge home).
Study or subgroup PN + Glutamine Standard PNMean
Difference WeightMean
Difference
N Mean(SD) N Mean(SD) IV,Fixed,95% CI IV,Fixed,95% CI
Brown 1998 16 28.25 (6.93) 16 37.44 (25.37) 1.4 % -9.19 [ -22.08, 3.70 ]
Pytlik 2002 21 13.5 (3.1) 19 11.27 (2.4) 77.2 % 2.23 [ 0.52, 3.94 ]
Schloerb 1993 16 26.9 (5.2) 13 32.7 (7.57) 9.6 % -5.80 [ -10.64, -0.96 ]
Ziegler 1992 22 29 (4.69) 20 36 (8.94) 11.8 % -7.00 [ -11.38, -2.62 ]
Total (95% CI) 75 68 100.0 % 0.22 [ -1.29, 1.72 ]
Heterogeneity: Chi2 = 23.74, df = 3 (P = 0.00003); I2 =87%
Test for overall effect: Z = 0.28 (P = 0.78)
Test for subgroup differences: Not applicable
-10 -5 0 5 10
PN + Glutamine Standard PN
46Nutrition support for bone marrow transplant patients (Review)
Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Analysis 2.2. Comparison 2 PN + glutamine versus standard PN, Outcome 2 Mean(+/-SD) cumulative
mucositis score.
Review: Nutrition support for bone marrow transplant patients
Comparison: 2 PN + glutamine versus standard PN
Outcome: 2 Mean(+/-SD) cumulative mucositis score
Study or subgroup PN + Glutamine Standard PNMean
DifferenceMean
Difference
N Mean(SD) N Mean(SD) IV,Fixed,95% CI IV,Fixed,95% CI
Brown 1998 18 0 (0) 16 0 (0) 0.0 [ 0.0, 0.0 ]
Pytlik 2002 21 13.5 (2.3) 19 12.6 (1.5) 0.90 [ -0.29, 2.09 ]
Schloerb 1993 16 0.7 (0.8) 13 0.9 (0.72) -0.20 [ -0.75, 0.35 ]
Ziegler 1992 24 2.1 (1.96) 20 2.2 (2.23) -0.10 [ -1.35, 1.15 ]
Total (95% CI) 79 68 -0.02 [ -0.48, 0.45 ]
Heterogeneity: Chi2 = 2.71, df = 2 (P = 0.26); I2 =26%
Test for overall effect: Z = 0.08 (P = 0.94)
Test for subgroup differences: Not applicable
-10 -5 0 5 10
PN + Glutamine Standard PN
47Nutrition support for bone marrow transplant patients (Review)
Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Analysis 2.3. Comparison 2 PN + glutamine versus standard PN, Outcome 3 Number of patients who
developed line infections from start to end of study..
Review: Nutrition support for bone marrow transplant patients
Comparison: 2 PN + glutamine versus standard PN
Outcome: 3 Number of patients who developed line infections from start to end of study.
Study or subgroup PN + Glutamine Standard PNPeto
Odds RatioPeto
Odds Ratio
n/N n/N Peto,Fixed,95% CI Peto,Fixed,95% CI
Brown 1998 0/18 0/16 0.0 [ 0.0, 0.0 ]
Pytlik 2002 0/1 0/1 0.0 [ 0.0, 0.0 ]
Schloerb 1993 0/16 0/13 0.0 [ 0.0, 0.0 ]
Ziegler 1992 0/24 0/21 0.0 [ 0.0, 0.0 ]
Total (95% CI) 59 51 0.0 [ 0.0, 0.0 ]
Total events: 0 (PN + Glutamine), 0 (Standard PN)
Heterogeneity: Chi2 = 0.0, df = 0 (P<0.00001); I2 =0.0%
Test for overall effect: Z = 0.0 (P < 0.00001)
Test for subgroup differences: Not applicable
0.1 0.2 0.5 1 2 5 10
PN + Glutamine Standard PN
48Nutrition support for bone marrow transplant patients (Review)
Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Analysis 2.4. Comparison 2 PN + glutamine versus standard PN, Outcome 4 Difference in mean % change
in body weight from start to end of the study between the trial groups..
Review: Nutrition support for bone marrow transplant patients
Comparison: 2 PN + glutamine versus standard PN
Outcome: 4 Difference in mean % change in body weight from start to end of the study between the trial groups.
Study or subgroup PN + Glutamine Standard PNMean
DifferenceMean
Difference
N Mean(SD) N Mean(SD) IV,Fixed,95% CI IV,Fixed,95% CI
Brown 1998 16 -6.85 (1.74) 15 -7.45 (2.54) 0.60 [ -0.94, 2.14 ]
Pytlik 2002 1 0 (0) 1 0 (0) 0.0 [ 0.0, 0.0 ]
Schloerb 1993 16 -0.61 (1.17) 13 0.56 (2.46) -1.17 [ -2.62, 0.28 ]
Ziegler 1992 24 0 (0) 21 0 (0) 0.0 [ 0.0, 0.0 ]
Total (95% CI) 57 50 -0.34 [ -1.40, 0.72 ]
Heterogeneity: Chi2 = 2.68, df = 1 (P = 0.10); I2 =63%
Test for overall effect: Z = 0.62 (P = 0.53)
Test for subgroup differences: Not applicable
-10 -5 0 5 10
Standard PN PN + Glut
49Nutrition support for bone marrow transplant patients (Review)
Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Analysis 2.5. Comparison 2 PN + glutamine versus standard PN, Outcome 5 Mean duration (+/-SD) that
nutritional intervention is given..
Review: Nutrition support for bone marrow transplant patients
Comparison: 2 PN + glutamine versus standard PN
Outcome: 5 Mean duration (+/-SD) that nutritional intervention is given.
Study or subgroup PN + Glutamine Standard PNMean
Difference WeightMean
Difference
N Mean(SD) N Mean(SD) IV,Fixed,95% CI IV,Fixed,95% CI
Brown 1998 18 23.22 (10.22) 16 18.81 (11.72) 7.1 % 4.41 [ -3.02, 11.84 ]
Pytlik 2002 21 3.5 (4.2) 19 2.8 (3.5) 69.3 % 0.70 [ -1.69, 3.09 ]
Schloerb 1993 16 30 (20) 13 31 (10.82) 3.0 % -1.00 [ -12.43, 10.43 ]
Ziegler 1992 24 26 (9.8) 20 28 (4.47) 20.6 % -2.00 [ -6.38, 2.38 ]
Total (95% CI) 79 68 100.0 % 0.36 [ -1.63, 2.35 ]
Heterogeneity: Chi2 = 2.39, df = 3 (P = 0.50); I2 =0.0%
Test for overall effect: Z = 0.35 (P = 0.72)
Test for subgroup differences: Not applicable
-10 -5 0 5 10
PN + Glutamine Standard PN
50Nutrition support for bone marrow transplant patients (Review)
Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Analysis 2.6. Comparison 2 PN + glutamine versus standard PN, Outcome 6 Number of patients who
developed >/=grade 2 graft versus host disease (GVHD)..
Review: Nutrition support for bone marrow transplant patients
Comparison: 2 PN + glutamine versus standard PN
Outcome: 6 Number of patients who developed >/=grade 2 graft versus host disease (GVHD).
Study or subgroup PN + Glutamine Standard PNPeto
Odds RatioPeto
Odds Ratio
n/N n/N Peto,Fixed,95% CI Peto,Fixed,95% CI
Brown 1998 0/18 3/16 0.10 [ 0.01, 1.08 ]
Pytlik 2002 0/1 0/1 0.0 [ 0.0, 0.0 ]
Schloerb 1993 0/16 0/13 0.0 [ 0.0, 0.0 ]
Ziegler 1992 6/24 5/20 1.00 [ 0.26, 3.88 ]
Total (95% CI) 59 50 0.57 [ 0.18, 1.83 ]
Total events: 6 (PN + Glutamine), 8 (Standard PN)
Heterogeneity: Chi2 = 2.69, df = 1 (P = 0.10); I2 =63%
Test for overall effect: Z = 0.95 (P = 0.34)
Test for subgroup differences: Not applicable
0.1 0.2 0.5 1 2 5 10
PN + Glutamine Standard PN
51Nutrition support for bone marrow transplant patients (Review)
Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Analysis 2.7. Comparison 2 PN + glutamine versus standard PN, Outcome 7 Number of days(+/-SD) to
achieve normal neutrophil level (>0.5 X 10/9/l) after day 0 of BMT..
Review: Nutrition support for bone marrow transplant patients
Comparison: 2 PN + glutamine versus standard PN
Outcome: 7 Number of days(+/-SD) to achieve normal neutrophil level (>0.5 X 10/9/l) after day 0 of BMT.
Study or subgroup PN + Glutamine Standard PNMean
DifferenceMean
Difference
N Mean(SD) N Mean(SD) IV,Fixed,95% CI IV,Fixed,95% CI
Brown 1998 17 14.88 (5.33) 14 17.36 (7.74) -2.48 [ -7.26, 2.30 ]
Pytlik 2002 1 0 (0) 1 0 (0) 0.0 [ 0.0, 0.0 ]
Schloerb 1993 16 14 (8) 13 15 (6.85) -1.00 [ -6.41, 4.41 ]
Ziegler 1992 24 20 (4.9) 20 18 (4.47) 2.00 [ -0.77, 4.77 ]
Total (95% CI) 58 48 0.57 [ -1.63, 2.76 ]
Heterogeneity: Chi2 = 2.91, df = 2 (P = 0.23); I2 =31%
Test for overall effect: Z = 0.51 (P = 0.61)
Test for subgroup differences: Not applicable
-10 -5 0 5 10
PN + Glutamine Standard PN
52Nutrition support for bone marrow transplant patients (Review)
Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Analysis 2.8. Comparison 2 PN + glutamine versus standard PN, Outcome 8 Actual numbers of patients
who have completed the study and survived to the 100th day post BMT..
Review: Nutrition support for bone marrow transplant patients
Comparison: 2 PN + glutamine versus standard PN
Outcome: 8 Actual numbers of patients who have completed the study and survived to the 100th day post BMT.
Study or subgroup PN + Glutamine Standard PNPeto
Odds RatioPeto
Odds Ratio
n/N n/N Peto,Fixed,95% CI Peto,Fixed,95% CI
Brown 1998 17/18 15/16 1.13 [ 0.07, 18.94 ]
Pytlik 2002 0/1 0/1 0.0 [ 0.0, 0.0 ]
Schloerb 1993 0/16 0/13 0.0 [ 0.0, 0.0 ]
Ziegler 1992 20/24 18/20 0.58 [ 0.10, 3.18 ]
Total (95% CI) 59 50 0.69 [ 0.16, 2.97 ]
Total events: 37 (PN + Glutamine), 33 (Standard PN)
Heterogeneity: Chi2 = 0.16, df = 1 (P = 0.69); I2 =0.0%
Test for overall effect: Z = 0.50 (P = 0.62)
Test for subgroup differences: Not applicable
0.1 0.2 0.5 1 2 5 10
PN + Glutamine Standard PN
53Nutrition support for bone marrow transplant patients (Review)
Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Analysis 2.9. Comparison 2 PN + glutamine versus standard PN, Outcome 9 Number of patients with
positive blood cultures.
Review: Nutrition support for bone marrow transplant patients
Comparison: 2 PN + glutamine versus standard PN
Outcome: 9 Number of patients with positive blood cultures
Study or subgroup PN + Glutamine Standard PNPeto
Odds RatioPeto
Odds Ratio
n/N n/N Peto,Fixed,95% CI Peto,Fixed,95% CI
Brown 1998 0/18 0/16 0.0 [ 0.0, 0.0 ]
Pytlik 2002 8/21 6/19 1.32 [ 0.37, 4.78 ]
Schloerb 1993 11/16 11/13 0.43 [ 0.08, 2.33 ]
Ziegler 1992 14/24 19/20 0.15 [ 0.04, 0.57 ]
Total (95% CI) 79 68 0.46 [ 0.20, 1.04 ]
Total events: 33 (PN + Glutamine), 36 (Standard PN)
Heterogeneity: Chi2 = 5.29, df = 2 (P = 0.07); I2 =62%
Test for overall effect: Z = 1.87 (P = 0.062)
Test for subgroup differences: Not applicable
0.1 0.2 0.5 1 2 5 10
Favours PN+Glutamine Favours Standard PN
54Nutrition support for bone marrow transplant patients (Review)
Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Analysis 3.1. Comparison 3 PN vs IV hydration, Outcome 1 Mean duration (+/-SD) of time in hospital (e.g.
from discharge admission to discharge or day 0 to discharge)..
Review: Nutrition support for bone marrow transplant patients
Comparison: 3 PN vs IV hydration
Outcome: 1 Mean duration (+/-SD) of time in hospital (e.g. from discharge admission to discharge or day 0 to discharge).
Study or subgroup Parenteral nutrition Intravenous hydratnMean
DifferenceMean
Difference
N Mean(SD) N Mean(SD) IV,Fixed,95% CI IV,Fixed,95% CI
Lough 1990 14 0 (0) 15 0 (0) 0.0 [ 0.0, 0.0 ]
Roberts 2003a 27 28.7 (8.8) 28 25.4 (4.3) 3.30 [ -0.38, 6.98 ]
Weisdorf 1987 71 0 (0) 66 0 (0) 0.0 [ 0.0, 0.0 ]
Total (95% CI) 112 109 3.30 [ -0.38, 6.98 ]
Heterogeneity: Chi2 = 0.0, df = 0 (P = 1.00); I2 =0.0%
Test for overall effect: Z = 1.76 (P = 0.079)
Test for subgroup differences: Not applicable
-10 -5 0 5 10
Favours PN Favours IV
55Nutrition support for bone marrow transplant patients (Review)
Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Analysis 3.2. Comparison 3 PN vs IV hydration, Outcome 2 Mean(+/-SD) number of days patients had some
degree of mucositis from start to end of study..
Review: Nutrition support for bone marrow transplant patients
Comparison: 3 PN vs IV hydration
Outcome: 2 Mean(+/-SD) number of days patients had some degree of mucositis from start to end of study.
Study or subgroup Parenteral nutrition Intravenous HydratnMean
DifferenceMean
Difference
N Mean(SD) N Mean(SD) IV,Fixed,95% CI IV,Fixed,95% CI
Lough 1990 14 0 (0) 15 0 (0) 0.0 [ 0.0, 0.0 ]
Roberts 2003a 27 0 (0) 28 0 (0) 0.0 [ 0.0, 0.0 ]
Weisdorf 1987 71 0 (0) 66 0 (0) 0.0 [ 0.0, 0.0 ]
Total (95% CI) 112 109 0.0 [ 0.0, 0.0 ]
Heterogeneity: Chi2 = 0.0, df = 0 (P<0.00001); I2 =0.0%
Test for overall effect: Z = 0.0 (P < 0.00001)
Test for subgroup differences: Not applicable
-10 -5 0 5 10
Favours PN Favours IV
56Nutrition support for bone marrow transplant patients (Review)
Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Analysis 3.3. Comparison 3 PN vs IV hydration, Outcome 3 Number of patients who developed line
infections from start to end of study..
Review: Nutrition support for bone marrow transplant patients
Comparison: 3 PN vs IV hydration
Outcome: 3 Number of patients who developed line infections from start to end of study.
Study or subgroup Parenteral nutrition Intravenous hydratnPeto
Odds RatioPeto
Odds Ratio
n/N n/N Peto,Fixed,95% CI Peto,Fixed,95% CI
Lough 1990 8/10 1/15 21.23 [ 4.15, 108.73 ]
Roberts 2003a 0/27 0/28 0.0 [ 0.0, 0.0 ]
Weisdorf 1987 0/71 0/66 0.0 [ 0.0, 0.0 ]
Total (95% CI) 108 109 21.23 [ 4.15, 108.73 ]
Total events: 8 (Parenteral nutrition), 1 (Intravenous hydratn)
Heterogeneity: Chi2 = 0.0, df = 0 (P = 1.00); I2 =0.0%
Test for overall effect: Z = 3.67 (P = 0.00025)
Test for subgroup differences: Not applicable
0.1 0.2 0.5 1 2 5 10
Favours PN Favours IV
57Nutrition support for bone marrow transplant patients (Review)
Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Analysis 3.4. Comparison 3 PN vs IV hydration, Outcome 4 Difference in mean % change in body weight
from start to end of the study between the trial groups..
Review: Nutrition support for bone marrow transplant patients
Comparison: 3 PN vs IV hydration
Outcome: 4 Difference in mean % change in body weight from start to end of the study between the trial groups.
Study or subgroup Parenteral nutrition Intravenous hydratnMean
DifferenceMean
Difference
N Mean(SD) N Mean(SD) IV,Fixed,95% CI IV,Fixed,95% CI
Lough 1990 10 -4.42 (2.3) 15 -7.18 (0.9) 2.76 [ 1.26, 4.26 ]
Roberts 2003a 27 -2 (13.8) 28 -6.5 (17.7) 4.50 [ -3.87, 12.87 ]
Weisdorf 1987 71 0 (0) 66 0 (0) 0.0 [ 0.0, 0.0 ]
Total (95% CI) 108 109 2.81 [ 1.34, 4.29 ]
Heterogeneity: Chi2 = 0.16, df = 1 (P = 0.69); I2 =0.0%
Test for overall effect: Z = 3.74 (P = 0.00018)
Test for subgroup differences: Not applicable
-10 -5 0 5 10
Favours IV Favours PN
58Nutrition support for bone marrow transplant patients (Review)
Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Analysis 3.5. Comparison 3 PN vs IV hydration, Outcome 5 Mean duration (+/-SD) that nutritional
intervention is given..
Review: Nutrition support for bone marrow transplant patients
Comparison: 3 PN vs IV hydration
Outcome: 5 Mean duration (+/-SD) that nutritional intervention is given.
Study or subgroup Parenteral nutrition Intravenous HydratnMean
DifferenceMean
Difference
N Mean(SD) N Mean(SD) IV,Fixed,95% CI IV,Fixed,95% CI
Lough 1990 14 10 (4) 15 0 (0) 0.0 [ 0.0, 0.0 ]
Roberts 2003a 27 17.5 (7.4) 28 5.3 (5.9) 12.20 [ 8.66, 15.74 ]
Weisdorf 1987 71 0 (0) 66 0 (0) 0.0 [ 0.0, 0.0 ]
Total (95% CI) 112 109 12.20 [ 8.66, 15.74 ]
Heterogeneity: Chi2 = 0.0, df = 0 (P = 1.00); I2 =0.0%
Test for overall effect: Z = 6.75 (P < 0.00001)
Test for subgroup differences: Not applicable
-10 -5 0 5 10
Favours PN Favours IV
59Nutrition support for bone marrow transplant patients (Review)
Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Analysis 3.6. Comparison 3 PN vs IV hydration, Outcome 6 Number of patients who developed > grade 2
graft versus host disease (GVHD)..
Review: Nutrition support for bone marrow transplant patients
Comparison: 3 PN vs IV hydration
Outcome: 6 Number of patients who developed > grade 2 graft versus host disease (GVHD).
Study or subgroup Parenteral nutrition Intravenous HydratnPeto
Odds RatioPeto
Odds Ratio
n/N n/N Peto,Fixed,95% CI Peto,Fixed,95% CI
Lough 1990 0/14 0/15 0.0 [ 0.0, 0.0 ]
Roberts 2003a 0/27 0/28 0.0 [ 0.0, 0.0 ]
Weisdorf 1987 0/71 0/66 0.0 [ 0.0, 0.0 ]
Total (95% CI) 112 109 0.0 [ 0.0, 0.0 ]
Total events: 0 (Parenteral nutrition), 0 (Intravenous Hydratn)
Heterogeneity: Chi2 = 0.0, df = 0 (P<0.00001); I2 =0.0%
Test for overall effect: Z = 0.0 (P < 0.00001)
Test for subgroup differences: Not applicable
0.1 0.2 0.5 1 2 5 10
Favours PN Favours IV
60Nutrition support for bone marrow transplant patients (Review)
Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Analysis 3.7. Comparison 3 PN vs IV hydration, Outcome 7 Number of days(+/-SD) to achieve normal
neutrophil level (>0.5 X 10/9/l) after day 0 of BMT..
Review: Nutrition support for bone marrow transplant patients
Comparison: 3 PN vs IV hydration
Outcome: 7 Number of days(+/-SD) to achieve normal neutrophil level (>0.5 X 10/9/l) after day 0 of BMT.
Study or subgroup Parenteral nutrition Intravenous hydratnMean
DifferenceMean
Difference
N Mean(SD) N Mean(SD) IV,Fixed,95% CI IV,Fixed,95% CI
Lough 1990 14 0 (0) 15 0 (0) 0.0 [ 0.0, 0.0 ]
Roberts 2003a 27 0 (0) 28 0 (0) 0.0 [ 0.0, 0.0 ]
Weisdorf 1987 71 0 (0) 66 0 (0) 0.0 [ 0.0, 0.0 ]
Total (95% CI) 112 109 0.0 [ 0.0, 0.0 ]
Heterogeneity: Chi2 = 0.0, df = 0 (P<0.00001); I2 =0.0%
Test for overall effect: Z = 0.0 (P < 0.00001)
Test for subgroup differences: Not applicable
-10 -5 0 5 10
Favours PN Favours IV
61Nutrition support for bone marrow transplant patients (Review)
Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Analysis 3.8. Comparison 3 PN vs IV hydration, Outcome 8 Actual numbers of patients who have
completed the study and survived to the 100th day post BMT..
Review: Nutrition support for bone marrow transplant patients
Comparison: 3 PN vs IV hydration
Outcome: 8 Actual numbers of patients who have completed the study and survived to the 100th day post BMT.
Study or subgroup Parenteral nutrition Intravenous hydratnPeto
Odds RatioPeto
Odds Ratio
n/N n/N Peto,Fixed,95% CI Peto,Fixed,95% CI
Lough 1990 0/14 0/15 0.0 [ 0.0, 0.0 ]
Roberts 2003a 0/27 0/28 0.0 [ 0.0, 0.0 ]
Weisdorf 1987 0/71 0/66 0.0 [ 0.0, 0.0 ]
Total (95% CI) 112 109 0.0 [ 0.0, 0.0 ]
Total events: 0 (Parenteral nutrition), 0 (Intravenous hydratn)
Heterogeneity: Chi2 = 0.0, df = 0 (P<0.00001); I2 =0.0%
Test for overall effect: Z = 0.0 (P < 0.00001)
Test for subgroup differences: Not applicable
0.1 0.2 0.5 1 2 5 10
Favours PN Favours IV
62Nutrition support for bone marrow transplant patients (Review)
Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Analysis 3.9. Comparison 3 PN vs IV hydration, Outcome 9 Actual number of patients who survived to day
200 post BMT..
Review: Nutrition support for bone marrow transplant patients
Comparison: 3 PN vs IV hydration
Outcome: 9 Actual number of patients who survived to day 200 post BMT.
Study or subgroup Parenteral nutrition Intravenous hydratnPeto
Odds RatioPeto
Odds Ratio
n/N n/N Peto,Fixed,95% CI Peto,Fixed,95% CI
Lough 1990 10/14 8/15 2.10 [ 0.48, 9.18 ]
Roberts 2003a 0/27 0/28 0.0 [ 0.0, 0.0 ]
Weisdorf 1987 0/71 0/66 0.0 [ 0.0, 0.0 ]
Total (95% CI) 112 109 2.10 [ 0.48, 9.18 ]
Total events: 10 (Parenteral nutrition), 8 (Intravenous hydratn)
Heterogeneity: Chi2 = 0.0, df = 0 (P = 1.00); I2 =0.0%
Test for overall effect: Z = 0.99 (P = 0.32)
Test for subgroup differences: Not applicable
0.1 0.2 0.5 1 2 5 10
Favours IV Favours PN
63Nutrition support for bone marrow transplant patients (Review)
Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Analysis 3.10. Comparison 3 PN vs IV hydration, Outcome 10 Mean % change in albumin.
Review: Nutrition support for bone marrow transplant patients
Comparison: 3 PN vs IV hydration
Outcome: 10 Mean % change in albumin
Study or subgroup PN Intravenous hydratioMean
DifferenceMean
Difference
N Mean(SD) N Mean(SD) IV,Fixed,95% CI IV,Fixed,95% CI
Lough 1990 10 -1.24 (5.3) 15 4.69 (4.4) -5.93 [ -9.90, -1.96 ]
Roberts 2003a 27 12.9 (6) 28 15.6 (4) -2.70 [ -5.41, 0.01 ]
Weisdorf 1987 71 0 (0) 66 0 (0) 0.0 [ 0.0, 0.0 ]
Total (95% CI) 108 109 -3.72 [ -5.96, -1.49 ]
Heterogeneity: Chi2 = 1.74, df = 1 (P = 0.19); I2 =42%
Test for overall effect: Z = 3.27 (P = 0.0011)
Test for subgroup differences: Not applicable
-10 -5 0 5 10
Favours IV Favours PN
64Nutrition support for bone marrow transplant patients (Review)
Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Analysis 4.1. Comparison 4 PN vs enteral feeding studies, Outcome 1 Mean duration (+/-SD) of time in
hospital (e.g. from admission to discharge or day 0 to discharge)..
Review: Nutrition support for bone marrow transplant patients
Comparison: 4 PN vs enteral feeding studies
Outcome: 1 Mean duration (+/-SD) of time in hospital (e.g. from admission to discharge or day 0 to discharge).
Study or subgroup Enteral ParenteralMean
DifferenceMean
Difference
N Mean(SD) N Mean(SD) IV,Fixed,95% CI IV,Fixed,95% CI
Cope 1997 23 0 (0) 40 0 (0) 0.0 [ 0.0, 0.0 ]
Szeluga 1987 30 0 (0) 31 0 (0) 0.0 [ 0.0, 0.0 ]
Young 1997 10 0 (0) 10 0 (0) 0.0 [ 0.0, 0.0 ]
Total (95% CI) 63 81 0.0 [ 0.0, 0.0 ]
Heterogeneity: Chi2 = 0.0, df = 0 (P<0.00001); I2 =0.0%
Test for overall effect: Z = 0.0 (P < 0.00001)
Test for subgroup differences: Not applicable
-10 -5 0 5 10
Favours Enteral Favours Parenteral
65Nutrition support for bone marrow transplant patients (Review)
Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Analysis 4.2. Comparison 4 PN vs enteral feeding studies, Outcome 2 Mean(+/-SD) number of days patients
had some degree of mucositis from start to end of study..
Review: Nutrition support for bone marrow transplant patients
Comparison: 4 PN vs enteral feeding studies
Outcome: 2 Mean(+/-SD) number of days patients had some degree of mucositis from start to end of study.
Study or subgroup Enteral ParenteralMean
DifferenceMean
Difference
N Mean(SD) N Mean(SD) IV,Fixed,95% CI IV,Fixed,95% CI
Cope 1997 23 0 (0) 40 0 (0) 0.0 [ 0.0, 0.0 ]
Szeluga 1987 30 0 (0) 31 0 (0) 0.0 [ 0.0, 0.0 ]
Young 1997 10 0 (0) 10 0 (0) 0.0 [ 0.0, 0.0 ]
Total (95% CI) 63 81 0.0 [ 0.0, 0.0 ]
Heterogeneity: Chi2 = 0.0, df = 0 (P<0.00001); I2 =0.0%
Test for overall effect: Z = 0.0 (P < 0.00001)
Test for subgroup differences: Not applicable
-10 -5 0 5 10
Favours enteral Favours parenteral
66Nutrition support for bone marrow transplant patients (Review)
Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Analysis 4.3. Comparison 4 PN vs enteral feeding studies, Outcome 3 Number of patients who developed
line infections from start to end of study..
Review: Nutrition support for bone marrow transplant patients
Comparison: 4 PN vs enteral feeding studies
Outcome: 3 Number of patients who developed line infections from start to end of study.
Study or subgroup Enteral ParenteralPeto
Odds RatioPeto
Odds Ratio
n/N n/N Peto,Fixed,95% CI Peto,Fixed,95% CI
Cope 1997 0/23 0/40 0.0 [ 0.0, 0.0 ]
Szeluga 1987 0/30 0/31 0.0 [ 0.0, 0.0 ]
Young 1997 0/10 0/10 0.0 [ 0.0, 0.0 ]
Total (95% CI) 63 81 0.0 [ 0.0, 0.0 ]
Total events: 0 (Enteral), 0 (Parenteral)
Heterogeneity: Chi2 = 0.0, df = 0 (P<0.00001); I2 =0.0%
Test for overall effect: Z = 0.0 (P < 0.00001)
Test for subgroup differences: Not applicable
0.1 0.2 0.5 1 2 5 10
Favours Enteral Favours Parenteral
67Nutrition support for bone marrow transplant patients (Review)
Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Analysis 4.4. Comparison 4 PN vs enteral feeding studies, Outcome 4 Difference in mean % change in body
weight from start to end of the study between the trial groups..
Review: Nutrition support for bone marrow transplant patients
Comparison: 4 PN vs enteral feeding studies
Outcome: 4 Difference in mean % change in body weight from start to end of the study between the trial groups.
Study or subgroup Enteral ParenteralMean
DifferenceMean
Difference
N Mean(SD) N Mean(SD) IV,Fixed,95% CI IV,Fixed,95% CI
Cope 1997 23 0 (0) 40 0 (0) 0.0 [ 0.0, 0.0 ]
Szeluga 1987 30 0 (0) 31 0 (0) 0.0 [ 0.0, 0.0 ]
Young 1997 10 0 (0) 10 0 (0) 0.0 [ 0.0, 0.0 ]
Total (95% CI) 63 81 0.0 [ 0.0, 0.0 ]
Heterogeneity: Chi2 = 0.0, df = 0 (P<0.00001); I2 =0.0%
Test for overall effect: Z = 0.0 (P < 0.00001)
Test for subgroup differences: Not applicable
-10 -5 0 5 10
Favours Parenteral Favours enteral
68Nutrition support for bone marrow transplant patients (Review)
Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Analysis 4.5. Comparison 4 PN vs enteral feeding studies, Outcome 5 Mean duration (+/-SD) that
nutritional intervention is given..
Review: Nutrition support for bone marrow transplant patients
Comparison: 4 PN vs enteral feeding studies
Outcome: 5 Mean duration (+/-SD) that nutritional intervention is given.
Study or subgroup Enteral ParenteralMean
DifferenceMean
Difference
N Mean(SD) N Mean(SD) IV,Fixed,95% CI IV,Fixed,95% CI
Cope 1997 23 0 (0) 40 0 (0) 0.0 [ 0.0, 0.0 ]
Szeluga 1987 30 0 (0) 31 0 (0) 0.0 [ 0.0, 0.0 ]
Young 1997 10 0 (0) 10 0 (0) 0.0 [ 0.0, 0.0 ]
Total (95% CI) 63 81 0.0 [ 0.0, 0.0 ]
Heterogeneity: Chi2 = 0.0, df = 0 (P<0.00001); I2 =0.0%
Test for overall effect: Z = 0.0 (P < 0.00001)
Test for subgroup differences: Not applicable
-10 -5 0 5 10
Favours enteral Favours parenteral
69Nutrition support for bone marrow transplant patients (Review)
Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Analysis 4.6. Comparison 4 PN vs enteral feeding studies, Outcome 6 Number of patients who developed >
grade 2 graft versus host disease (GVHD)..
Review: Nutrition support for bone marrow transplant patients
Comparison: 4 PN vs enteral feeding studies
Outcome: 6 Number of patients who developed > grade 2 graft versus host disease (GVHD).
Study or subgroup Enteral ParenteralPeto
Odds RatioPeto
Odds Ratio
n/N n/N Peto,Fixed,95% CI Peto,Fixed,95% CI
Cope 1997 0/23 0/40 0.0 [ 0.0, 0.0 ]
Szeluga 1987 0/30 0/31 0.0 [ 0.0, 0.0 ]
Young 1997 0/10 0/10 0.0 [ 0.0, 0.0 ]
Total (95% CI) 63 81 0.0 [ 0.0, 0.0 ]
Total events: 0 (Enteral), 0 (Parenteral)
Heterogeneity: Chi2 = 0.0, df = 0 (P<0.00001); I2 =0.0%
Test for overall effect: Z = 0.0 (P < 0.00001)
Test for subgroup differences: Not applicable
0.1 0.2 0.5 1 2 5 10
Favours enteral Favours parenteral
70Nutrition support for bone marrow transplant patients (Review)
Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Analysis 4.7. Comparison 4 PN vs enteral feeding studies, Outcome 7 Number of days(+/-SD) to achieve
normal neutrophil level (>0.5 X 10/9/l) after day 0 of BMT..
Review: Nutrition support for bone marrow transplant patients
Comparison: 4 PN vs enteral feeding studies
Outcome: 7 Number of days(+/-SD) to achieve normal neutrophil level (>0.5 X 10/9/l) after day 0 of BMT.
Study or subgroup Enteral ParenteralMean
DifferenceMean
Difference
N Mean(SD) N Mean(SD) IV,Fixed,95% CI IV,Fixed,95% CI
Cope 1997 23 0 (0) 40 0 (0) 0.0 [ 0.0, 0.0 ]
Szeluga 1987 30 0 (0) 31 0 (0) 0.0 [ 0.0, 0.0 ]
Young 1997 10 0 (0) 10 0 (0) 0.0 [ 0.0, 0.0 ]
Total (95% CI) 63 81 0.0 [ 0.0, 0.0 ]
Heterogeneity: Chi2 = 0.0, df = 0 (P<0.00001); I2 =0.0%
Test for overall effect: Z = 0.0 (P < 0.00001)
Test for subgroup differences: Not applicable
-10 -5 0 5 10
Favours enteral Favours parenteral
71Nutrition support for bone marrow transplant patients (Review)
Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Analysis 4.8. Comparison 4 PN vs enteral feeding studies, Outcome 8 Actual numbers of patients who have
completed the study and survived to the 100th day post BMT..
Review: Nutrition support for bone marrow transplant patients
Comparison: 4 PN vs enteral feeding studies
Outcome: 8 Actual numbers of patients who have completed the study and survived to the 100th day post BMT.
Study or subgroup Enteral ParenteralPeto
Odds RatioPeto
Odds Ratio
n/N n/N Peto,Fixed,95% CI Peto,Fixed,95% CI
Cope 1997 0/23 0/40 0.0 [ 0.0, 0.0 ]
Szeluga 1987 0/30 0/31 0.0 [ 0.0, 0.0 ]
Young 1997 0/10 0/10 0.0 [ 0.0, 0.0 ]
Total (95% CI) 63 81 0.0 [ 0.0, 0.0 ]
Total events: 0 (Enteral), 0 (Parenteral)
Heterogeneity: Chi2 = 0.0, df = 0 (P<0.00001); I2 =0.0%
Test for overall effect: Z = 0.0 (P < 0.00001)
Test for subgroup differences: Not applicable
0.1 0.2 0.5 1 2 5 10
Favours enteral Favours parenteral
72Nutrition support for bone marrow transplant patients (Review)
Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Analysis 4.9. Comparison 4 PN vs enteral feeding studies, Outcome 9 Actual number of patients who have
completed the study and survived beyond day 200 post BMT..
Review: Nutrition support for bone marrow transplant patients
Comparison: 4 PN vs enteral feeding studies
Outcome: 9 Actual number of patients who have completed the study and survived beyond day 200 post BMT.
Study or subgroup Enteral ParenteralPeto
Odds RatioPeto
Odds Ratio
n/N n/N Peto,Fixed,95% CI Peto,Fixed,95% CI
Cope 1997 0/23 0/40 0.0 [ 0.0, 0.0 ]
Szeluga 1987 0/30 0/31 0.0 [ 0.0, 0.0 ]
Young 1997 0/10 0/10 0.0 [ 0.0, 0.0 ]
Total (95% CI) 63 81 0.0 [ 0.0, 0.0 ]
Total events: 0 (Enteral), 0 (Parenteral)
Heterogeneity: Chi2 = 0.0, df = 0 (P<0.00001); I2 =0.0%
Test for overall effect: Z = 0.0 (P < 0.00001)
Test for subgroup differences: Not applicable
0.1 0.2 0.5 1 2 5 10
Favours enteral Favours parenteral
Analysis 5.1. Comparison 5 Oral eicosapentaenoic acid supplementation versus nil, Outcome 1 Numbers
not developing graft versus host disease.
Review: Nutrition support for bone marrow transplant patients
Comparison: 5 Oral eicosapentaenoic acid supplementation versus nil
Outcome: 1 Numbers not developing graft versus host disease
Study or subgroup Treatment Control Odds Ratio Weight Odds Ratio
n/N n/N M-H,Fixed,95% CI M-H,Fixed,95% CI
Takatsuka 2002 3/8 0/9 100.0 % 12.09 [ 0.52, 280.40 ]
Total (95% CI) 8 9 100.0 % 12.09 [ 0.52, 280.40 ]
Total events: 3 (Treatment), 0 (Control)
Heterogeneity: not applicable
Test for overall effect: Z = 1.55 (P = 0.12)
Test for subgroup differences: Not applicable
0.1 0.2 0.5 1 2 5 10
Favours treatment Favours control
73Nutrition support for bone marrow transplant patients (Review)
Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
A D D I T I O N A L T A B L E S
Table 1. Summary table - Quality of studies assessed
Study ID Randomisation Allocation con-
ceal
Double blind Participants
masked
Clinicians
masked
Assessors
masked
Anderson 1998 Truly random Adequate Yes Yes Yes Yes
Jebb 1995 Unclear Unclear Yes Yes Yes Yes
Schloerb 1999 Truly random Adequate Yes Yes Yes Yes
Coghlin
Dickson 2000
Unclear Unclear Yes Yes Unclear Unclear
Brown 1998 Truly random Adequate Yes Yes Yes Yes
Schloerb 1993 Truly random Adequate Yes Yes Yes Yes
Ziegler 1992 Unclear Adequate Yes Yes Yes Uncertain
Lough 1990 Truly random Adequate No No No No
Weisdorf 1987 Unclear Unclear No Uncertain Uncertain Uncertain
Szeluga 1987 Unclear Unclear No Uncertain Uncertain Uncertain
Young 1997 Unclear Unclear No Uncertain Uncertain Uncertain
Cope 1997 Unclear Unclear No Uncertain Uncertain Uncertain
Macburney
1994
Unclear Unclear Yes Yes Yes Yes
Scheltinga 1991 Unclear Unclear Yes Yes Yes Uncertain
Young 1993 Unclear Unclear Yes Yes Yes Yes
Ziegler 1998 Unclear Unclear Yes Uncertain Uncertain Uncertain
Charhuas 1997 Unclear Unclear Yes Yes Yes Yes
Mulder 1989 Unclear Unclear No Uncertain Uncertain Uncertain
Lenssen 1998 Unclear Unclear Uncertain Uncertain Uncertain Uncertain
74Nutrition support for bone marrow transplant patients (Review)
Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Table 1. Summary table - Quality of studies assessed (Continued)
Aldamiz 1996 Unclear Unclear Uncertain Uncertain Uncertain Uncertain
Lenssen 1987 Truly random Adequate Yes Yes Yes Yes
Jimenez 1999
Malhotra 1996 Unclear Unclear Uncertain Uncertain Uncertain Uncertain
Muscaritoli
1998
Unclear Unclear No No No Uncertain
Takatsuka 2002 Unclear Unclear No Uncertain Uncertain Uncertain
Roberts 2003a Unclear Unclear No No No Uncertain
Pytilik 2002 Truly random Adequate Yes Yes Yes Yes
Santos 2001 Truly random Adequate Uncertain Uncertain Uncertain Uncertain
Aquino 2005 Truly random Adequate Yes Unclear Unclear Unclear
A P P E N D I C E S
Appendix 1. Example search strategy
#1 explode “Nutrition”/ all subheadings
#2 explode “Nutrition-Assessment”/ all subheadings
#3 explode “Feeding-Methods”/ all subheadings
#4 “Intubation,-Gastrointestinal”/ all subheadings
#5 “Gastrostomy”/ all subheadings
#6 “Eating”/ all subheadings
#7 explode “Foods,-Specialized”/ all subheadings
#8 explode “Food”/ all subheadings
#9 explode “Feeding-Behavior”/ all subheadings
#10 explode “Appetite”/ all subheadings
#11 “Jejunostomy”/ all subheadings
#12 “Glutamine”/ all subheadings
#13 glutamin*
#14 nutrition*
#15 food*
#16 feed*
#17 nasogastr*
#18 nasojejun*
#19 nasoduoden*
#20 gastrostom*
75Nutrition support for bone marrow transplant patients (Review)
Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
#21 gastrojejunostom*
#22 naso near duoden*
#23 naso near1 gastr*
#24 jejun*
#25 bolus*
#26 intub*
#27 appetite*
#28 parenteral*
#29 calor*
#30 intake*
#31 sip*
#32 oral*
#33 diet*
#34 intraven*
#35 enteral*
#36 tube*
#37 supplement*
#38 fortif*
#39 formula*
#40 eat*
#41 hydrolysate*
#42 novel* substrate*
#43 elemental
#44 PN in TI,TO,CM,AB
#45 EN in TI,TO,CM,AB
#46 TPN in TI,TO,CM,AB
#47 NG in TI,TO,CM,AB
#48 PEG in TI,TO,CM,AB
#49 “Bone-Marrow-Transplantation”/ all subheadings
#50 bone marrow near transplan*
#51 Peripheral blast stem cell transplan*
#52 BMT*
#53 MATCH* SIB* DON*
#54 MATCH* UNREL* DON*
#56 PBSCT*
#57 #1 or #2 or #3 or #4 or #5 or #6 or #7 or #8 or #9 or #10 or #11 or #12 or #13 # or #14 or #15 or #16 or #17 or #18 or #19 or #
20 or #21 or #22 or #23 or #24 or #5 or #26 or #27 or #28 or #29 or #30 or #31 or #32 or #33 or #34 or #35 or #36 or #37 or #38
or #39 or #40 or #41 or #42 or #43 or #44 or #45 or #46 or #47 or #48
#58 #49 or #50 or #51 or #52 or #53 or #54 or #55 or #56
#59 #57 and #58
F E E D B A C K
76Nutrition support for bone marrow transplant patients (Review)
Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Including the study by Pytlik 2002, 2 October 2013
Summary
With regard to the analysis ’Parenteral nutrition with glutamine versus standard parenteral nutrition’ I would respectfully ask the authors
to consider the appropriateness of including the study by Pytlik 2002. The intervention group received daily GLN supplementation
from day +1 to day +14 of transplant regardless of their need for PN. In fact the intervention group received PN for just 3.5 days on
average. Hence this study was not of glutamine supplemented PN.If there is a benefit of GLN it is likely to be in those patients requiring
nutritional support as per the other studies originally included (Ziegler and Schloerb). Subsequent studies have shown a benefit in
allogeneic but not autologous transplant patients - if this review were to be updated it would be very useful to see meta-analysis per
transplant type“
Name: Julie Beckerson
Affiliation: Imperial College Healthcare NHS Trust
Role: Haematology Dietitian
Reply
The inclusion criteria for this review were: Study type- Randomised Controlled Trial, Patient type - receiving any type of bone marrow
transplant, and the Type of Intervention- must compare one form of enteral or parenteral nutrition with another mode of nutrition
support or IV fluid. There was no minimum or maximum duration specified for receiving the intervention.
With the Pytilik 2002 study, the intervention group received daily GLN supplementation from day +1 to day +14 of transplant
regardless of their need for PN. The intervention group received PN for just 3.5 days on average.
The duration for receiving the PN with or without GLN (albeit for an average of 3.5 days ) was not a reason for excluding this study.
The hypothesis being that we do not know the optimum duration for receiving the intervention. This remains an included study.
In a future update a meta-analysis for the different types of transplants would be worthy to investigate.
Contributors
Susan Murray, Royal College of Physicians.
W H A T ’ S N E W
Last assessed as up-to-date: 30 April 2008.
Date Event Description
4 April 2014 Amended This review has been withdrawn. Please see Published notes.
77Nutrition support for bone marrow transplant patients (Review)
Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
H I S T O R Y
Protocol first published: Issue 1, 2001
Review first published: Issue 2, 2002
Date Event Description
4 April 2014 Feedback has been incorporated Feedback added regarding a query about the appro-
priateness of the Pytilik 2002 study for inclusion. See
Feedback.
12 November 2008 Amended Contact details updated
13 August 2008 Amended This review update should have been put up for publi-
cation in Issue 3, 2008 but unfortunately due to tech-
nical error did not make it
14 May 2008 Amended Converted to new review format.
30 April 2008 New citation required and conclusions have changed This review is made up of four small sub reviews. For
the update of this review 17 potential studies were
identified in the re-run of the search which was con-
ducted in June 2006. Five of the 17 studies were in-
cluded, three of which were grouped within three other
reviews which are included in this review that is:
Oral Glutamine versus placebo (one study Aquino
2005 (n = 120 children)), Parenteral nutrition (PN)
with Glutamine versus standard PN (one study Pytilik
2002 (n = 40)) and Parenteral nutrition versus Intra-
venous hydration (one study Roberts 2003 (n = 55))
. The two other studies were not pooled but added to
the eight other heterogenous studies identified in the
original review
The addition of data from the studies by Aquino 2005
and Roberts 2003 does not affect the results or conclu-
sions of the sub reviews that they were part of. How-
ever, for the sub review that compared PN with addi-
tional glutamine versus standard PN, following further
analysis with the additional data from Pytilik 2002 the
pooled result for hospital duration did not show the
same benefit to patients who received the interven-
tion PN with Glutamine in that, hospital duration no
longer seemed to be reduced for patients who received
the intervention. However, the likelihood that these
patients will have less infections remains the same. In
the original review of this material we proposed that
for patients who were unable to have an adequate oral
diet and who had gastrointestinal failure resulting in
the need for PN, PN with added glutamine should be
78Nutrition support for bone marrow transplant patients (Review)
Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
(Continued)
considered. We would now alter this to say that giv-
ing patients PN with additional glutamine could be of
benefit but also further research on this is required to
further confirm this.
Previous readers of this review would benefit from
reading this updated review
C O N T R I B U T I O N S O F A U T H O R S
SM & SP both worked on the protocol, review and the update with SM primarily writing up the revisions to the text for the update.
D E C L A R A T I O N S O F I N T E R E S T
None known
N O T E S
This review is now out of date although it is correct as of the date of publication [Issue 4, 2008]. The original author team is unable
to complete the update, hence the decision to withdraw.
We are seeking new authors to develop a new protocol which would serve to update the existing review and incorporate the latest
evidence into a new Cochrane Review. However, we would suggest that the current topic is too broad and would therefore recommend
reassessing the title prior to registration. Please contact PaPaS if you are interested: http://papas.cochrane.org/contact-us.
I N D E X T E R M SMedical Subject Headings (MeSH)
∗Enteral Nutrition; ∗Parenteral Nutrition; Bone Marrow Transplantation [∗adverse effects]; Fluid Therapy [methods]; Glutamine
[administration & dosage]; Length of Stay; Malnutrition [etiology; ∗prevention & control]; Randomized Controlled Trials as Topic
MeSH check words
Humans
79Nutrition support for bone marrow transplant patients (Review)
Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.