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APLASTICAPLASTIC

ANEMIAANEMIA

Dairion Gatot, Soegiarto Gani, Savita HandayaniDivision of Hematology-Medical Onkology

Departement of Internal Medicine

Faculty of Medicine, Sumatera Utara University

2!

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D"FI#I$IO#

* Pancytopenia with markedly hypocellular marrow

* Incidence world wide is 2 to 5 cases/million population/year

* Severe aplastic anemia has been defined as marrow of

less than 25 % celularity or less than 50 % hemopoieticcells with at least two of the followin!"

# $bsolute neutrophil count less than 500/l

# Platelet count of less than 20&000/l

# 'orrected reticulocyte inde( of less than )

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%&$HO'"#"SIS

* echanism of patho!enesis

# Intrinsic stem cell defect

# +ailure of stromal microenvironment

# ,rowth factor defect or dificiency# Immune suppression of marrow

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* $c-uired

# 'hemicals

# .ru!s

# adiation # iruses

# iscellaneous

"$IO(O')

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* 1ereditary

# +aconi $nemia

# $utosomal recessive

# $bnormal skin pi!mentation

# 'hromosome fra!ility

# .yskeratosis con!enita may evolve into aplastic

anemia

# Schwachman # .iamond syndrome

* Idiopathic

"$IO(O')

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*(I#I*&( F"&$U+"S

* +ati!ue bleedin! or infections as a conse-uence

of cytopenias

* Physical e(amination !enerally is unrevealin! e(cept for si!ns of anemia bleedin! or infections

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(&O+&$O+) F"&$U+"S

* Pancytopenia

* ow reticulocyte inde(3 red cells may be macrocytic

* arkedly hypocellular marrow

* ow $bsolute neutrophil count

* $bnormal cyto!enetic findin!s su!!est hypoplastic

myelodysplastic syndrome rather than aplastic anemia

* 4e!ative sucrose hemolysis test to rule out P41

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D"F"+"#$I&( DI&'#OSIS OF

%*)$O%"#I& H)%O%(&S$I* M&++O.

)& 1ypoplastic myelodysplastic syndrome

2& Paro(ysmal nocturnal hemo!lobinuria

& 1ypoplastic acute lymphocytic leukemia

6& 1airy cell leukemia

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BMP and biopsy :

for the determination of cellularity and exclusion of other

diseases!he presence of blasts or abundant mega"aryocytes is not

compatible #ith the diagnosis of $$

Diagnostic considerations

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$a/le !0 *lassification of aplastic anemia /y counts0

Severe &&

%$&' ( )**+ul

%$' ( -*,***+ul in anemic

+tranfusion.dependent patients

%Platelets ( /* x 0*1 +ul

/ out of 1 criteria

Moderate &&

$$ not fulfilling severity criteria

in Diagnosis of chronic M$$

re2uires persistent moderately

depressed counts 3 1 months

$bbreviations: $&', absolute neutrophil count4 $', absolute reticulocyte

count4 M$$, moderate $$

Jaroslaw P. Maciejewski and Antonio M. Risitano

$merican Society of Hematology /**)

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*(I#I*&( *OU+S"

edian survival of untreated severe

aplastic anemia is to 7 months

820 % survive lon!er than ) year9

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$+"&$M"#$

* arrow transplantation is curative

* Indicated in patients less than 60 years of a!e with and

1$#related matched or ) anti!en mismatched donor

* :nly :ne#third of patients have a suitable donor

* ;5 to

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$+"&$M"#$

* Immunosupressive therapy " not curative

* $ntithymocyte !lobulin 8$>,9

# 50 % response rate

# dose " )5 to 60 m!/k! intravenously for 6 to )0 days

# fever chills common on first day of treatment

# accelerated platelet destruction with

thrombocytopenia fre-uent

# serum sickness common with fever rash ? arthral!ias

occurrin! ; to )0 days after be!innin! treatment

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$+"&$M"#$

* 'yclosporine 8'SP9

# primary treatment or in patients refractory to $>,

# dose" to ; m!/k! daily orally for at least 6 to 7

months # dose ad@usted to maintain proper blood levels

# renal impairment common side effect

# 25 % of patients respond overall 8 ran!e of response

is 0 to

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$+"&$M"#$

* 'ombinations

#$>, and 'SP may yield an improved response rate

# as hi!h as 5; % of patients in one series showed lon!

term se-uelae if immunosupressive therapy after

< years such as "

# recurrent aplasia

# P41

# acute myelo!enous leukemia

# myelodysplastic syndrome

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$+"&$M"#$

* $ndro!en as primary therapy has not been efficacious

in severe or moderate aplastic anemia

* 1emopoietic !rowth factors have been used to treat

neutropenia

# >emporary improvement in neutrophil count has been observed with ,#'S+ or ,#'S+ treatment in some

patients

# I# !ave temporary improvement in the absolute

neutrophil count in a few patients # I# ) was not effective in a small !roup of patients

5 G.'S7 8 'ombination #ith an $!G+'s$ regimen,

. 6mprove neutropenia and response to this therapy constitutes

an early positive prognostic factor

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$+"&$M"#$

* Support 'are

# Immediate 1$ typin! of patient and siblin!s as

possible marrow donors

# inimal or no transfusions in potential transplant

recipients # If transfusions are needed do not use family donors in

a potential transplant recipients

# >ransfuse platelets based on assessment of risk of

bleedin! and not solely on platelet count # Sin!le donor platelets should be used to minimiAe 1$

sensitiAation and subse-uent refractoriness

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$+"&$M"#$

* Support 'are # Bse of leukocyte#depleted blood products helps to reduce

sensitiAation

# >ransfuse packed C'Ds when hemo!lobin level is less

than ; to < !/dl # :btain ' serolo!y for prospective transplant recipients

# 4eutropatic precautions for hospitaliAed patients with

absolute neutrophill counts of less than 500

# Prompt institution of board spectrum I antibiotics forfever after appropriate cultures have been obtained

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%rotocol $1erapy *onservative t1erapies

Immunosuppression 3IS4

0 Horse 9$!Gam at /* mg+"g per day for - days

/ abbit $!G 9!hymoglobulin at 1) mg+"g per day for ) days

Horse $!Gespon rate ;*.

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Respon criteria :

Was defined improvement of blood count

(complete or partial) Within 4 month.

Complete Remission (CR) :

1. Haemoglobin (Hb) level was normal for

the patient age

. !eutrophils "1#$ % 1&.'l

. *latelets "1$& + 1&.&,

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*artial Remission (*R) :

Was defined b- transfusion independence and

b- an unsupported increase in counts atleast one cell line over the baseline

value:

( Hb level b- at least gdl#

!eutrophil b- at least $ % 1&'l#

f previousl- lower than $ % 1&'l#

and platelet b- at least & + 1&',#

f previous lower than & + 1&',# )

or b- doubling# or normali/ation of counts

of at least one cell lineif previous counts of the respective cell

line(s)did not meet the criteria for 0