O R I G I N A L A R T I C L E

Efficacy and safety of peripheral blood stem cell mobilization andcollection: a single-center experience in 190 allogeneic donors_3619 1..8

Cristina Rinaldi, Chiara Savignano, Samantha Pasca, Alessandra Sperotto, Francesca Patriarca,

Miriam Isola, Renato Fanin, and Vincenzo De Angelis

BACKGROUND: In the past two decades peripheralblood stem cells (PBSCs) have increasingly replacedmarrow as stem cells source for allogeneic transplanta-tion. The PBSC donation initially applied only to relateddonors; later, due to the safety of the procedure, it wasextended to unrelated donors.STUDY DESIGN AND METHODS: We have retrospec-tively collected data regarding mobilization, collection,and short- and long-term follow-up of 190 consecutivedonors, 174 related and 16 unrelated. All donors fol-lowed a standard protocol for mobilization and under-went at least one PBSC collection. Follow-up in relateddonors was performed every 4 months in the first yearand then annually, with no time limits, while unrelateddonors were monitored for 10 years.RESULTS: All 190 donors completed the establishedmobilization protocol. The mobilizing capacity was sig-nificantly greater in males and in donors less than 60years old. No case of major toxicity by granulocyte–colony-stimulating factor was found, nor thromboembo-lic events. The total dose of CD34+/recipient (median5.8 ¥ 106/kg recipient/body weight) was statistically cor-related with age, CD34+ before and after mobilization,and collection efficiency. Compliance to follow-up was66%, with a significant difference between related andunrelated (63% vs. 100%, p = 0.03). During follow-upno significant abnormalities in hematologic variables orhematologic malignancies were reported.CONCLUSION: Our study allowed us to define thePBSC donation as “a safe procedure for the donors,”with short- and long-term effects limited to a small per-centage of donors and “effective for the recipient,” dueto the dose of collected CD34+, adequate for transplan-tation in almost all recipients.

In the past two decades peripheral blood stem cell(PBSC) collection has increasingly replaced bonemarrow harvest. Today 99% of autologous and 71%of allogeneic transplantations come from PBSCs.1

This trend began in the early 1990s and has been consoli-dated over time,2 as reported in the annual European BoneMarrow Transplantation (EBMT) activity survey. Thereasons for this shift are well known: higher CD34+ celldose collected, fast cell recovery, less blood componentsupport and graft-versus-leukemia effect; most recentlythis type of donation has been favored by the introductionof reduced-intensity conditioning regimens. The PBSCdonation initially involved only related donors; later,according to the accumulation of evidence on PBSC dona-tion safety, this type of donation was extended to unre-lated donors. In our country, the standards of the ItalianBone Marrow Donor Registry (IBMDR) allowed this typeof donation since January 2005, with a significant delaycompared to other international registries. Parallel to theincrease in PBSC donation, in 2008, for the first time inEurope, the number of matched unrelated donorsexceeded that of HLA-identical sibling donors. The spreadof reduced-intensity conditioning and nonmyeloablativeregimens associated with the use of peripheral bloodsource expanded the number of patients eligible to

ABBREVIATIONS: AE(s) = adverse event(s); FVG = Friuli

Venezia Giulia; HPC-A = hematopoietic progenitor cells–

apheresis; IBMDR = Italian Bone Marrow Donor Registry;

PBSC(s) = peripheral blood stem cell(s).

From the Transfusion Medicine Department and the Clinic of

Haematology, University Hospital of Udine, and the Depart-

ment of Statistics, University of Udine, Udine, Italy.

Address reprint requests to: Samantha Pasca, Transfusion

Medicine Department, University Hospital of Udine, P.le S.

Maria della Misericordia, 15, Udine, Italy; e-mail: sampasca@

alice.it.

Received for publication September 20, 2011; revision

received January 25, 2012, and accepted January 26, 2012.

doi: 10.1111/j.1537-2995.2012.03619.x

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transplant, resulting in an increased number of potentialdonors, even among those of advanced age and inpresence of comorbidities,1,3,4 so that Al-Ali and col-leagues5 have defined the current scenario of stemcell transplantation as “. . . the era of older familydonors. . . .” At the same time of the spread of PBSC dona-tion, doubts have been raised on side effects recorded inthe short and long term in PBSC donors, compared tothose in marrow donors.6-10 In the light of recent evidenceof the existence of a small, but definite risk of severecomplications and fatalities in the short and longperiod, the international transplant community suggestedthe application of long-term follow-up protocols forrelated donors, already provided for unrelated donors.11

The aim was to evaluate the safety of PBSC donation inrelated and unrelated donors during short- and long-termfollow-up and to analyze factors affecting CD34+ mobili-zation capacity and collection efficacy, to optimize donorselection.

MATERIALS AND METHODS

Study design and study populationA total of 190 consecutive volunteer donors, 174 relatedand 16 matched unrelated donors, referred to UniversityHospital of Udine from 1996 to 2010, were retrospectivelyconsidered in this study. All donors underwent mobiliza-tion with granulocyte–colony-stimulating factor (G-CSF),followed by hematopoietic progenitor cells–apheresis(HPC-A) and entered a follow-up program after dona-tion. The medical evaluation to assess medical suitabilityincluded general health and medical history collectionby direct questioning and screening questionnaire (withparticular attention to thrombophilia, atherosclerosis,ischemic heart disease, epilepsy, autoimmune diseases,risk of prion disease, risk factors for transmission ofhuman immunodeficiency virus, hepatitis B or C, neo-plastic diseases, inflammatory diseases, pregnancy, orbreast-feeding) and laboratory and instrumental tests. Alldonors received extensive oral and written explanationson the procedures and potential effects or risks associ-ated with the mobilization and collection. All donorssigned informed consent to treatment, according to hos-pital ethics committee. The exceptions to eligibility crite-ria, established by local and international guidelines,were applied exclusively in related donors, where theurgency of the transplant did not allow the retrieval ofalternative sources of stem cells, after a careful examina-tion of the risks to the donor and the benefits to therecipient, always respecting and protecting the health ofboth and with agreement of both. Age of at least 65 yearsin related donors (upper limit of blood donation accord-ing to Italian transfusion law) did not represent a reasonfor exclusion.

MobilizationG-CSF mobilization protocols were as follows:

1. In HLA full-matched sibling and IBMDR donors:lenograstim (Granocyte 34f33, Sanofi-Aventis, Spa,Milan, Italy) 10 mg/kg body weight/daily, single-dosesubcutaneous administration for 4-6 days.

2. In haploidentical related donors: filgrastim (Neupo-gen, Amgen Dompé, Milan, Italy) 12 to 16 mg/kg bodyweight/daily, single-dose subcutaneous administra-tion for 4-5 days.

Collection (HPC-A)HPC-A started on Day +5 from onset of mobilization (Day1 was conventionally the first day of G-CSF administra-tion) and proceeded on Days +6 and +7, if the target doseof CD34+ was not reached. Target doses were, respectively:1) CD34+ at least 4.0 ¥ 106/kg recipient body weight inHLA-full-matched transplants and 2) CD34+ at least9.0 ¥ 106/kg recipient body weight in haploidenticaltransplants.

HPC-A procedures were performed with an apheresissystem (COBE Spectra, CaridianBCT, Lakewood, CO),MNC protocol. The median processed blood volume wastwo times the total blood volume of each donor.

Follow-up

Related donorsFollow-up controls were planned every 4 months in thefirst year after donation and then annually, with no timelimits. Before 2005 the follow-up was limited to 2 to 3 yearsafter donation, in accordance with the physician’s evalu-ation. The follow-up program was conducted by the phy-sicians of the transplant unit (Clinic of Haematology).

Unrelated donorsAccording to IBMDR standards, follow-up controls weremade on Days +2, +7, and +30; on Months +6 and +12; andthen annually for 10 years. The follow-up program wasconducted by the physicians of the apheresis unit (Trans-fusion Medicine Department).

Statistical analysesQuantitative variables were described in terms of means,standard deviations, median, and range. For qualitativevariables absolute and relative frequency distribution wascalculated. Quantitative variables were tested for normaldistribution using the Shapiro-Wilk test. Comparisonsbetween groups were performed with t test or Mann-Whitney U test, depending on Shapiro-Wilk test results.

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Chi-square tests were used to analyze categorical values;when assumptions for chi-square test were not verified,Fisher’s exact test was used.

Pearson’s correlation or Spearman’s correlationanalyses were used to explore possible associationbetween quantitative variables, depending on the datadistribution. Results were considered significant whenp values were not more than 0.05. Statistical analyses wereperformed using computer software (SPSS 18 forWindows, SPSS, Inc., Chicago, IL).

RESULTS

A total of 190 consecutive donors are included in thisstudy, covering a 15-year period (1996-2010); baselinecharacteristics are shown in Table 1.

MobilizationAll the 190 donors completed the established mobilizationprotocol without interruption; no donor required hospi-talization during the treatment with G-CSF. In 12 donors itwas necessary to reduce the scheduled growth factordosage on Day +4, because of white blood cell (WBC)count of at least 50 ¥ 109/L.

The peak of CD34+, the first day of collection, was onaverage 68.5 mL (range, 14-225 mL). The other variablesrelated to mobilization are summarized in Table 2.

In univariate analysis the value of peripheral bloodCD34+ before mobilization was predictive of postmobili-zation value (Fig. 1). The age was inversely correlated withthe ability to mobilize (Fig. 2). The mobilizing capacity

(peak of CD34+) was significantly greater in males (78.5 mLvs. 59.5 mL, p < 0.001) and in donors less than 60 years(70 mL vs. 48 mL, p = 0.006; Figs. 3 and 4).

In only one case, a female over 60 years old, the peak ofCD34+ after mobilization was 14 mL. In 13 of 190 donors(6.8%) the peak of CD34+ after mobilization was less than30 mL. The statistical analysis reported in Table 3 comparesthe groups with peak values of less than or 30 mL or moreand showed that the only predictor of poor mobilizationwas the number of CD34+ cells before mobilization.

No case of major toxicity by G-CSF was found. Inthree donors, postmobilization WBC count was more than70 ¥ 109 cells/L, despite a dose reduction of G-CSF on Day+4. The prevalence of short-term adverse events (AEs)was statistically higher in unrelated donors than relateddonors (100% vs. 84%, p = 0.005) and in males (males 98%

TABLE 1. Baseline characteristics of donors

CharacteristicsNumber(median) Range or %

SexMales 105/190 55Females 85/190 45

TypologyRelated 174/190 92Unrelated (IBMDR) 16/190 8

Age (years) 44 18-72Weight (kg) 72 45-125Place of origin

FVG region 133/190 70Italy (outside FVG region) 48/190 25Other countries (outside Italy) 9/190 5

TABLE 2. Variables related to mobilizationVariable Median Range

G-CSF (mg/kg/day) 10 10-16CD34+ (mL)

Basal, before mobilization 2.8 0.8-7.5First day of collection 68.5 14-225

WBC count (¥109/L)Basal, before mobilization 6.0 3.0-12.4First day of collection 46.6 18.6-78.0

Fig. 1. Correlation of CD34+ before and after mobilization

(Spearman’s r = 0.487, p < 0.0001).

Fig. 2. Correlation of CD34+ after mobilization and age of

donor (Spearman’s r = -0.204, p = 0.005).

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vs. females 83%, p = 0.005); there were no differencesrelated to age. Bone pain was the most common AE, com-plained of by 81% of the donors, headache by 22%, andflu-like symptoms by 13%. Other reported AEs were oneallergic reaction in the G-CSF administration site; threecases of conjunctivitis; three cases of pain in the spleniclodge (negative to ultrasound check); one attack of gout;

one periodontal abscess; and one bronchopneumonia,with onset 6 days after donation. No thromboemboliccomplications related to G-CSF were registered.

Collection (HPC-A)The 190 donors underwent a total of 246 HPC-A proce-dures (median, 1; range 1-3); most donors (61.5%) reachedthe target dose with a single collection procedure, onlyone donor required three leukapheresis procedures.

Only two related donors, females, needed femoralvenous access for collection. Postcollection platelet (PLT)decrease was on average 42% (range, 6%-72%). In 13donors (6.8%) postdonation PLT counts were between30 ¥ 109 and 50 ¥ 109/L; thrombocytopenia was nevercomplicated by bleeding. The median of CD34+ cells col-lected and calculated by weight of the recipient was5.8 ¥ 106/kg (range, 1.1 ¥ 106-22.0 ¥ 106/kg). The total doseof CD34+/kg recipient was statistically correlated withage, CD34+ before mobilization, CD34+ after mobiliza-tion, and collection efficiency (Table 4).

The CD34+ cell collected dose was significantly differ-ent between the two sexes (males, 6.4 ¥ 106/kg recipient;females, 5.2 ¥ 106/kg recipient). In 26 donors at least 60years old, the median dose of collected CD34+ cells was4.6 ¥ 106/kg recipient, significantly less than the dose col-lected in 164 donors less than 60 years (median of5.9 ¥ 106/kg recipient).

The target dose of CD34+ cells (�4 ¥ 106/kg recipient)was achieved in 80% of HLA-full-matched donors, a non-optimal yield in 16% of donors (CD34+ <4 ¥ 106/�2 ¥ 106/kg), with only 4% of donors collecting a CD34+ dose lessthan 2 ¥ 106/kg recipient.

Only four leukapheresis procedures were stoppedbefore the scheduled end: three due to symptomatichypocalcemia (carpal spasm) unresponsive to supple-mentation therapy and one due to anaphylactoid reactionto anticoagulant (ACD-A). The prevalence of symptomatichypocalcemia was statistically higher in females versusmales (79% vs. 25%, p < 0.0001); moreover, it also inverselycorrelated with the weight of donors (p < 0.0001).

Follow-upThe compliance of the donors to follow-up was 66%. Atotal of 125 of 190 donors performed at least one of the

scheduled controls after donation. Themedian length of follow-up was 21months (range, 1-124 months). Compli-ance was higher among the unrelated(IBMDR) compared to related donors(100% vs. 63%, p = 0.003). This probablyreflects the fact that all unrelated donorslived in the Friuli Venezia Giulia (FVG)region, while the origin of the related

Fig. 3. CD34+ peak after mobilization, males versus females

(Mann-Whitney test, p < 0.0001).

Fig. 4. CD34+ peak after mobilization: less than 60 years

versus more than 60 years (Mann-Whitney test, p = 0.006).

TABLE 3. CD34+ after mobilization (<30 mL vs. �30 mL)

Variable

CD34+ after mobilization

<30 mL �30 mL p value

Number D 13/190 177/190 NSSex (male/female) 6/7 99/78 NSAge (years), mean (range) 50 (30-66) 44 (18-72) NSCD34+ (mL) before mobilization 1.4 (1.0-2.0) 2.9 (0.8-7.5) <0.001WBC count (¥109) before mobilization 5.6 6.2 NS

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donors was quite different: 117 of 174 (68%) from FVG, 48of 174 (28%) from other Italian regions, and 9 of 174 (5%)from foreign countries. Compliance among the relateddonors was significantly higher among residents in FVG(74% vs. 40%, p < 0.0001). The impact of the condition ofthe recipient (living/deceased) on adherence to the post-donation controls was also evaluated. Donors withdeceased recipients showed a tendency toward loweradherence than donors with living recipients (58% vs.70%), although the difference was not significant. Neithersex nor age correlated with the donor compliance atfollow-up. During short-term follow-up on Days +1 and+30 from PBSC collection, the 16 unrelated donors filled ina written questionnaire concerning the satisfaction ofdonation, according to IBMDR standards.

The donation experience was judged positively by 15of 16 donors; the care of physicians and nurses wasdefined good by 16 of 16. The majority of donors (15/16)did not notice any change in their physical and psycho-logical condition while one female donor reported amarked improvement in her mood. All except one wouldbe available to a subsequent donation. For related donorswritten satisfaction questionnaires were not provided. Theassessment of hematologic variables before mobilizationand during follow-up (+6 months and +12 months)showed no significant changes in the values of WBCs,hemoglobin, and PLTs, compared to predonation values.

Table 5 summarizes the diseases diagnosed duringfollow-up, limited to clinically significant diseases and theones requiring hospitalization. No cases of hematologicmalignancy have been reported.

DISCUSSION

The experience of the University Hospital of Udine in allo-geneic hematopoietic stem cell transplantation covers 20years, and peripheral blood source was used in the alloge-neic setting since 1996, anticipating a trend later observedworldwide. During the period of this study (1996-2010),the approach of the transplant community to the PBSCdonation has considerably changed. After initial workdemonstrating an acceptable risk for PBSC donors,12,13 theattention of clinicians was focused almost exclusively oneffectiveness of mobilization, collection, and recipientoutcome, sometimes forgetting the rights and the needs ofthe donors. Over the past decade it has been recognizedthat the PBSC donation is not risk free; the selection cri-teria of donors adhered to standards defined by the inter-national bone marrow registry and enforced into nationallegislations, with the aim of protecting the health of boththe donor and the recipient, so that the donors have fullyrecovered their leading role. Our study included 190donors: 16 unrelated, from the IBMDR registry, all resi-dents in the FVG region, and 174 related, 30% of whichcame from other Italian regions or foreign countries.

Our case series confirms the effectiveness of themobilization protocol used, with a median peak of CD34+after mobilization of 68.5 mL (range, 14-225 mL). Similar toreports by other authors,4,5,14-16 univariate statistical analy-sis showed that the mobilization capacity, after G-CSFadministration, correlates negatively with age and femalesex. These variables can be usefully considered in unre-lated donor choice, but have less clinical relevance infamily setting where options are never quite possible.

We have been able to confirm data from de la Rubiaand colleagues17 and Brown and colleagues,18 showing thatCD34+ in steady state, before G-CSF administration, pre-dicts the efficacy of mobilization. This value, easy to obtainduring donor workup, can be a useful tool in related donor

TABLE 4. Correlation CD34+/kg recipient versusvariables of D and CD34+/kg recipient versus

efficiencyVariable Spearman’s test p value*

Age -0.333 <0.001Weight (kg) -0.024 NSCD34+ (mL)

Before mobilization 0.413 <0.001After mobilization 0.661 <0.001

WBC count (¥109/L)Basal, before mobilization 0.195 0.011First collection day 0.301 <0.001

Efficiency of CD34+ collection 0.211 0.005

* Significant correlation p = 0.01.

TABLE 5. Diseases, clinically significant, diagnosed in the donors during follow-upDiagnosis Number of donors Age at diagnosis (years) Sex Months from donation Follow-up (months)

Amyotrophic lateral sclerosis 1 65 Female 12 38 (donor died)Mixed connectivitis 1 48 Female 12 96Monoclonal gammopathy of

undeterminated significance1 51 Male 26 89

Epstein-Barr virus relapse 1 43 Female 27 27Deep vein thrombosis 1 56 Female 28 124Colon cancer with metastases 1 59 Female 35 47 (donor died)Breast cancer 1 46 Female 41 57Follicular thyroid cancer 1 71 Female 66 66Ischemic cardiopathy 1 65 Male 74 98Papillary thyroid cancer 1 64 Female 84 102Pulmonary sarcoidosis 1 67 Male 85 87Squamous cell cancer (face) 1 65 Female 96 102

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selection, especially in older ones, to prevent mobilizationfailures; alternatively, in case of low steady-state CD34+value, physicians can increase G-CSF dosage or, in thefuture, associate G-CSF with one of the new mobilizingagents.

Even our study has highlighted a wide individual vari-ability among donors in response to G-CSF, which does notallow us to draw a definite profile of the “poor mobilizer.”The study also faced the critical issues related to the increas-ing age of the donors and the impact of older age on mobi-lization capacity and incidence of AEs. We consideredseparately donors 60 years and older and donors less than60 years old. The peak of CD34+ after mobilization,although significantly less in the older than in the youngerdonors, did not affect adversely the PBSC collection andrecipient transplantation. The effects of G-CSF administra-tion and collection were not different in the two groups.Conversely with Lysak and coworkers,4 but according toAl-Ali and coworkers,5 in our study the age was not “a priori”a criterion for exclusion from donation, in the absence ofcomorbidities that could negatively affect the collection.

Also in our study, as previously published in othercase series,9,19-21 80% of donors reached the target dose fortransplantation (CD34+ �4 ¥ 106/kg recipient in HLA-full-matched transplants). We registered only 4% (7/190) fail-ures of PBSC collection (CD34+ <2.0 ¥ 106/kg recipient),requiring marrow harvest or a second donor mobilization,but we could not identify predictive variables others thanthe female sex and the premobilization CD34+, alreadymentioned.

No cases of severe toxicity from G-CSF, requiring thesuspension of treatment or the hospitalization, were reg-istered in our case series. Conversely with that publishedby Halter and coworkers,10 in our study no cases of signifi-cant cardiovascular or thromboembolic complicationswere found within 30 days from donation. The strictadherence to donor selection criteria, provided by trans-fusion law and IBMDR standards, both in related and inunrelated settings, explains these results; in fact, no donorat increased cardiovascular or thrombotic risk was admit-ted to PBSC donation.

Mobilization side effects were observed more fre-quently in unrelated donors than in related ones (100% vs.85%); this observation can be ascribed to the differencesin collecting data regarding side effects in the two groups:related donors were interviewed directly, while unrelateddonors were asked to fill in a questionnaire at +1 and +30days from donation, according to IBMDR standards. Inaddition, related donors, being more involved with recipi-ents and having stronger motivation than unrelateddonors, may accept a greater level of morbidity or under-report side effects.

The compliance of donors to follow-up controls washigh (66%), if compared with other studies which havefocused attention on this topic,19,22,23 even if the median

length of follow-up was only 21 months (range, 1-124months). The difference in compliance between relatedand unrelated donors (63% vs. 100%, p = 0.03) can beascribed to the different management of postdonationcontrols (see “Study design and study population”).Another reason lies in the residence, being far away fromthe donation center for 33% of related donors (livingoutside the FVG region in other Italian regions or foreigncountries), while all the unrelated donors lived in the FVGregion. Thus, we can confirm previously reported resultsthat this geographic variable impacts significantly on thecompliance to follow-up.23 According to the same report,23

still in our case the state of the related recipient (living ordeceased) had an impact on compliance to follow-up; thegreater compliance was seen in the donor with recipientliving (58% vs. 70%).

The assessment of hematologic variables at 6 and 12months after the donation did not show the presence ofsignificant cytopenias, as previously reported by Martinoand colleagues,22 but in contrast with other studies,19,24

which showed reductions in WBC counts, persistent untilthe third to fourth year after donation.

The clinically relevant diseases diagnosed in donorsduring follow-up are barely related to the mobilizationand collection procedures. While the G-CSF might haveplayed a role in the case of mixed connectivitis diagnosed12 months after the donation, as described by otherauthors,25 it is difficult to establish a causal link betweenthe use of G-CSF and the onset of ischemic heart diseaseat a distance of 74 months from donation. The case ofamyotrophic lateral sclerosis does not appear to be relatedto G-CSF, despite the close temporal relationship with thedonation (onset 4 months after donation).

In conclusion, our study on 190 allogeneic donors hasallowed us to define the PBSC donation as “a safe proce-dure for the donor,” burdened with limited short- andlong-term side effects and “effective for the recipient,” dueto the dose of collected CD34+ cells, nearly alwaysadequate for recipient transplantation. However, theonset of clinically significant events and neoplastic dis-eases, at a distance of several years from donation, sug-gests the need to extend follow-up, possibly lifelong.Donors lost at follow-up should be contacted and asked toundergo annual medical controls, to collect more compre-hensive data on long-term safety of PBSC donation.

CONFLICT OF INTEREST

The authors declare no conflict of interest relative to this paper.

REFERENCES

1. Baldomero H, Gratwohl M, Gratwohl A, Tichelli A, Nieder-

wieser D, Madrigal A, Frauendorfer K; for the European

Group for Blood and Marrow Transplantation EBMT. The

RINALDI ET AL.

6 TRANSFUSION Volume **, ** **

EBMT activity survey 2009: trend over the past 5 years.

Bone Marrow Transplant 2011;46:485-501.

2. Gratwohl A, Baldomero H. Trend of hematopoietic stem

cell transplantation in third millennium. Curr Opin

Hematol 2009;16:420-6.

3. Rhodes B, Anderlini P. Allogeneic peripheral blood stem

cell collection as of 2008. Transfus Apher Sci 2008;38:219-

27.

4. Lysak D, Koristek Z, Gasova Z, Skoumalová I, Jindra P. Effi-

cacy and safety of peripheral blood cell collection in

elderly donors; does age interfere? J Clin Apher 2010;26:9-

16.

5. Al-Ali HK, Burgeois M, Krahl R, Edel E, Leiblein S, Poenisch

W, Basara N, Lange T, Niederwieser D. The impact of the

age of HLA-identical siblings on mobilization and collec-

tion of PBSCs for allogeneic hematopoietic cell transplan-

tation. Bone Marrow Transplant 2010;6:1-7.

6. Pulsipher MA, Chitphakdithai P, Miller JP, Logan BR, King

RJ, Rizzo JD, Leitman SF, Anderlini P, Haagenson MD,

Kurian S, Klein JP, Horowitz MM, Confer DL. Adverse

events among 2408 unrelated donors of peripheral blood

stem cells: results of a prospective trial from National

Marrow Donor Program. Blood 2009;113:3604-11.

7. Siddiq S, Pamphilon D, Brunskill S, Doree C, Hyde C, Stan-

worth S. Bone marrow harvest versus peripheral stem cell

collection for haemopoietic stem cell donation in healthy

donors. Cochrane Database Syst Rev 2009;(1):CD006406.

8. Miller JP, Perry EH, Price TH, Bolan CD Jr, Karanes C, Boyd

TM, Chitphakdithai P, King RJ. Recovery and safety profiles

of marrow and PBSC donors: experience of the National

Marrow Donors Program. Biol Blood Marrow Transplant

2008;14 Suppl:29-36.

9. Holig K, Kramer M, Kroschinsky F, Bornhäuser M, Men-

gling T, Schmidt AH, Rutt C, Ehninger G. Safety and effi-

cacy of hematopoietic stem cell collection from mobilized

peripheral blood in unrelated volunteers: 12 years of

single-center experience in 3928 donors. Blood 2009;114:

3757-63.

10. Halter J, Kodera Y, Ispizua AU, Greinix HT, Schmitz N,

Favre G, Baldomero H, Niederwieser D, Apperley JF,

Gratwohl A. Severe events in donors after allogeneic

hematopoietic stem cell donation. Haematologica 2009;94:

94-101.

11. Anderlini P. Effects and safety of granulocyte colony-

stimulating factor in healthy volunteers. Curr Opin

Hematol 2009;16:35-40.

12. Anderlini P, Przepiorka D, Seong D, Miller P, Sundberg J,

Lichtiger B, Norfleet F, Chan KW, Champlin R, Körbling M.

Clinical toxicity and laboratory effects of granulocyte-

colony-stimulating factor (filgrastim) mobizilation and

blood stem cell apheresis from normal donors, and analy-

sis of charges for the procedures. Transfusion 1996;36:590-

95.

13. Anderlini P, Przepiorka D, Champlin R, Körbling M.

Biologic and clinical effects of granulocyte-colony

stimulating factor normal individuals. Blood 1996;88:2819-

25.

14. Vasu S, Leitman SF, Tisdale JF, Hsieh MM, Childs RW,

Barrett AJ, Fowler DH, Bishop MR, Kang EM, Malech HL,

Dunbar CE, Khuu HM, Wesley R, Yau YY, Bolan CD. Donor

demographic and laboratory predictors of allogeneic

peripheral blood stem cell mobilization in an ethnically

diverse population. Blood 2008;112:2092-100.

15. Wang TF, Wen SH, Chen RL, Lu CJ, Zheng YJ, Yang SH, Chu

SC, Kao RH, Chen SH. Factors associated with peripheral

blood stem cell yield in volunteer donors mobilized with

granulocyte colony-stimulating factors: the impact of

donor characteristics and procedural settings. Biol Blood

Marrow Transplant 2008;14:1305-11.

16. Richa E, Papari M, Allen JA, Martinez G, Wickrema A,

Anastasi J, Van Besien K, Artz A. Older age but not donor

health impairs allogeneic granulocyte colony-stimulating

factor (G-CSF) peripheral blood stem cell mobilization.

Biol Blood Marrow Transplant 2009;15:1394-9.

17. de la Rubia J, Lorenzo JI, Torrebadella M, Marín P, Insunza

A, Sanz MA. Basal CD34+ cell count predicts peripheral

blood progenitor cell mobilization and collection in

healthy donors after administration of granulocyte

colony-stimulating factor. Haematologica 2004;89:

1530-2.

18. Brown RA, Adkins D, Goodnough LT, Haug JS, Todd G,

Wehde M, Hendricks D, Ehlenbeck C, Laub L, DiPersio J.

Factors that influence the collection and engraftment of

allogenic peripheral-blood stem cells in patients with

hematological malignancies. J Clin Oncol 1997;15:

3067-74.

19. de la Rubia J, de Arriba F, Arbona C, Pascual MJ, Zamora C,

Insunza A, Martínez D, Paniagua C, Díaz MA, Sanz MA.

Follow-up of healthy donors receiving granulocyte colony-

stimulating factor for peripheral blood progenitor cell

mobilization and collection. Results of the Spanish Donor

Registry. Haematolgica 2008;93:735-40.

20. Lysák D, Koza V, Jindra P. Factors affecting PBSC mobiliza-

tion and collection in healthy donors. Transfus Apher Sci

2005;33:275-83.

21. Martino M, Cllea I, Condemi A, Dattola A, Irrera G, Mar-

cuccio D, Messina G, Pontari A, Pucci G, Console G, Laco-

pino P. Predictive factors that affect the mobilization of

CD34+ cells in healthy donors treated with recombinant

granulocyte colony-stimulating factor (G-CSF). J Clin

Apher 2006;26:169-75.

22. Martino M, Console G, Dattola A, Callea I, Messina G,

Moscato T, Massara E, Irrera G, Fedele R, Gervasi A,

Bresolin G, Iacopino P. Short and long-term safety of

lenograstim administration in healthy peripheral haemato-

poietic progenitor cell donors: a single centre experience.

Bone Marrow Transplant 2009;44:163-8.

23. Leitner GC, Baumartner K, Kahls P, Biener D, Greinix HT,

Hoecker P, Worel N. Regeneration, health status and

quality of life after rhG-CSF-stimulated stem cell collection

EFFICACY AND SAFETY OF PBSC COLLECTION

Volume **, ** ** TRANSFUSION 7

in healthy donors: a cross-sectional study. Bone Marrow

Transplant 2009;43:357-63.

24. Tassi C, Razzari PL, Bonifazi F, Giudice V, Nannetti A, Ricci

F, Rizzi S, Bandini G, Conte R. Short and long-term hae-

matological surveillance of healthy donors allogeneic

peripheral haematopoietic progenitors mobilized with

G-CSF: a single institution prospective study. Bone Marrow

Transplant 2005;36:289-94.

25. Anderlini P, Champlin RE. Biologic and molecular effects

of granulocyte colony-stimulating factor in healthy

individuals: recent findings and current challenges. Blood

2008;111:1767-72.

RINALDI ET AL.

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