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Original Article
Acquired severe aplastic anemia treated with
antithymocyte globulin and cyclosporine: An experience
of regional cancer center, Western India
Ankit B. Patel, Harsha P. Panchal, Asha S. Anand, Apurva A. Patel, Sonia P. Parikh, Sandip A. Shah
Department of Medical and Paediatric Oncology, Gujarat Cancer and Research Institute, Ahmedabad, Gujarat, India

Address for correspondence: Dr. Ankit B Patel, Medical OPD Room No. 80, Gujarat Cancer and Research Institute, New Civil Campus, Asarwa,
Ahmedabad, Gujarat, India. E‑mail: ankit_ahm1985@yahoo.com

ABSTRACT
Severe aplastic anemia (SAA) is a serious bone marrow disease that needs a comprehensive and service-intense treatment with either bone
marrow transplantation (BMT) or immunosuppressive therapy (IST); both are difficult to optimally offer in resources-limited countries. Here,
we report the outcome of IST using horse Antithymocyte globulin (ATG) in 18 (7 children; 11 adults) patients with SAA referred to our center
in west India. Only 18 patients out of 102 diagnosed as AA in 2 years could receive IST, largely due to costs restraints. Although CR was
seen in 30% in adults and 33% in pediatric cases, but overall 50% cases were able to enjoy transfusion‑independence, requiring no further
treatment. Treatment related mortality occurred in 6.2%, relapse in 6.2% and 6.2% had clonal evolution. This makes IST a valuable option
for managing SAA in absence of bone marrow transplantation.
Key words: Antithymocyte globulin, aplastic anemia, cyclosporine, Western India

INTRODUCTION SUBJECTS AND METHODS

Aplastic anemia (AA) is an uncommon but serious
disorder characterized by peripheral blood (PB)
cytopenias resulting from acquired factors causing failure
of the bone marrow (BM) to produce blood cells. BM
transplantation (BMT) is the treatment of choice for
the majority of patients especially young patients but is
unfortunately limited due to various factors including
the cost of treatment, non‑availability of expertise or
matched donors. As acquired AA is thought to be caused
by immune damage including T‑cell related immune
destruction, immunosuppressive therapy (IST) has a
role. Several studies have shown encouraging results with
a combination of antithymocyte globulin (ATG) and
cyclosporine (CSA)[1,2] in improving survival compared
with supportive care alone,[3,4] with response rates vary
between 40% and 70% and short‑term survival similar
to unselected patients treated with BMT.[5,6]
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In this retrospective study, all patients who were
treated with ATG and CSA from January 2011 to
December 2012 were included and followed up for at
least 1 year at Gujarat Cancer and Research Institute,
Ahmedabad with permission of Institutional Review
Board. The disease was considered severe AA (SAA) if
hypocellular marrow was associated with at least two
of the following: a neutrophil count of <0.5 × 109/L,
a platelet count of <20 × 109/L, and a reticulocyte
count of <1%.[7] AA was considered very SAA (VSAA)
if the criteria for severe disease were fulfilled and the
neutrophil count was below 0.2 × 109 L. Chromosomal
fragility test was not available. However, patients were
screened for any phenotypic manifestation of Fanconi’s
and all had no family history of intrinsic BM failure
syndrome or of consanguinity. Only 4 patients were
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How to cite this article: Patel AB, Panchal HP, Anand AS, Patel AA,
DOI: Parikh SP, Shah SA. Acquired severe aplastic anemia treated with
antithymocyte globulin and cyclosporine: An experience of regional
10.4103/1658-5127.160198
cancer center, Western India. J Appl Hematol 2015;6:53-7.

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Patel, et al.: Acquired severe aplastic anemia treated with ATG and Cyclosporine

screened for paroxysmal nocturnal hemoglobinuria Pretreatment characteristics of study population are
by immunophenotyping and the rest had a negative shown in Table 1. The median follow‑up time was
sucrose lysis test. Viral markers HIV, HBsAg, HCV 20 months (13–35). One pediatric patient died within
were negative in all patients and history of chemical 1 month due to intracranial hemorrhage and one adult
and radiation exposure was ruled out. No specific cause patient was lost to follow‑up (LFU) within 1 month
was found all patients. after taking ATG, so 2 patients were excluded from
analysis. Finally, 10 adults (9 AA: 1 VSAA) and 6
All patients were treated with horse ATG at a dose of
40 mg/kg for 8 days or 80 mg/kg for 4 days through pediatrics (5 AA: 1 VSAA) were analyzed for response
a central line over 4–6 h infusion. A test dose of [Table 2]. 6 months after treatment, 6 out of 10 (60%)
ATG (0.1 ml in 10 ml on forearm) was given before adult patients had remission (1 had CR and 5 had PR)
first course of ATG. Premedication with hydrocortisone and in pediatric subset, only 1 patient out of 6 (16.7%)
and pheniramine maleate was given before daily dose of had PR. At the end of 1 year, 5 out of 10 (50%) adult
ATG. For the prevention of serum sickness, intravenous patients had remission ‑ 3 CR and 2 PR (2 PR converted
methylprednisolone was given at 2 mg/kg divided in CR and 1 patient had relapse on 200 days and in
into 0.5 mg/kg 6 hourly doses over 8 days followed pediatric subset 2 out of 6 (33%) had remission ‑ 1
by tapering protocol of 1.5 mg/kg divided into two had CR and 1 had PR. One child had delayed response
equal doses on day 9, 10 then 1.0 mg/kg divided on achieving CR at 430 days. So finally, 50% response rate
day 11, 12; 0.5 mg/kg on day 13, 14, and 0.25 mg/kg
given on 15th day. CSA was started at 10 mg/kg orally
Table 1: Pretreatment characteristics of study
on day 1 and continued for responding patients until population initially included (n=18)
they become transfusion independent and for at least
Study population Adult (11) Pediatric (7)
1 year with monitoring of CSA level every week for
Median age 35 (16-58) 9 (7-13)
the first 2 weeks and then once every 2 weeks for the
Sex
remainder of the treatment or as necessary to maintain
Male:Female 8:3 4:3
a whole‑blood CSA level between 200 and 500 ng/ml. Duration of symptoms* 1.5 (1-6) months 1.2 (1-3) months
Those who failed to respond discontinued treatment Fever n (%) 5 (45) 4 (57)
after 6 months of treatment. Bleeding n (%) 6 (54) 4 (57)
Hb (g/dl) 7.3 (5.4-11.1) 6.2 (3.5-11.2)
Response Criteria and Toxicity
Absolute reticulocyte 1 (0.5-1.7) 0.9 (0.8-1.5)
Complete response (CR) was defined as transfusion count (×109/L)
independence and a neutrophil count >1.5 × 109/L, a ANC count (×109/L)* 0.6 (0.18-1.2) 0.6 (1.1-1.4)
platelet count >100 × 109/L, and a hemoglobin (Hb) Platelets (×109/L)* 7 (3-64) 5 (2-17)
level of >10 g/dl. Partial response (PR) was defined as *Values in mean. ANC=Absolute neutrophil count; Hb=Hemoglobin
transfusion independence and an unsupported increase
of counts of at least one cell line over baseline values (Hb
Table 2: Overall response rate of treated patients
by at least 2 g/dl and actual value ≥8 g/dl: neutrophils
according to time (n=16)
by at least 0.5 × 109/L and platelets >30 × 109/L, if
previously lower than 20 × 109/L) in patients with Duration Adult Pediatrics
SAA or VSAA.[1,2,8,9] All remissions were confirmed by CR PR No response CR PR No response
6 months 1 5*,# 4 0 1 5
2 blood counts at least 4 weeks apart. Clinical relapse
12 months 3 2 5 1 1 4
was defined by the return of PB counts to levels
18 months 3 2 5 2 1 3
meeting the definition of severe or moderate AA and
At present 3 2 5 2 1 3
the requirement for blood transfusion.[1,2] Toxicity of
*One patient relapsed after getting PR, #2 patients converted into CR.
treatment was evaluated and graded according to the CR=Complete response; PR=Partial response
criteria of World Health Organization.[10]

RESULTS Table 3: Kinetics (median time) of recovery of

PB count (n=16)
T h e re w e re 1 8   p a t i e n t s . O f w h i c h , 7 w e re Hematological parameters In days
pediatric (4 male: 3 female) and 11 were adult Hb 153 (60-320)
patients (8 male: 3 female), who were treated for ANC >500 64 (30-150)
aplastic anemia with ATG and CSA between January ANC >1000 110 (50-260)
2011 and December 2012. Median age of pediatric Platelet 96 (50-160)
patients was 9 years and of adult patients was 35 years. PB=Peripheral blood; Hb=Hemoglobin; ANC=Absolute neutrophil count

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Patel, et al.: Acquired severe aplastic anemia treated with ATG and Cyclosporine

in pediatric patients (2 CR: 1 PR). Both patient with 2 years could receive IST, largely due to costs restraints.
VSAA responded, 1 had PR and 1 had CR. Table 3 This also may be compounded by challenges in delivering
shows overall response rate according to time. such an important treatment at the optimal time.

Four out of seven (2 adults and 2 children), non There is a paucity of literature pertaining to responses
responders are alive and on supportive care at present. of ATG and CSA in AA from developing world. The
Of remaining three, one adult patient later on develops results of the present study show that an overall
acute myeloid leukemia (AML) and died, and remaining response within 6 months in adult patients was
two were LFU. Patients who did not respond were 60% and 16.7% in children. More rapid response to
supported by regular blood transfusion to maintain treatment may results in lower rates of early death,
Hb >7 g/dl. Platelet transfusions were given for clinically less need of supportive care, less use of resources, and
evident bleeding and in the asymptomatic patient if thereby lower cost.[9]
platelets <10,000. Episodes of febrile neutropenia were
managed with broad spectrum antibiotics. Late presentations and referrals, difficulties in making
ATG/CSA optimally available, associated comorbidities
Kinetics of Remission and Recovery of Peripheral and complications, constraints in supportive care
Blood Counts like antifungal, antibacterials, and isolation may all
Blood counts of all 8 (5 adult: 3 children) patients, contribute to the relatively unsatisfactory results.
who responded showed an improvement in at least
one cell line within 3 months. Median time of recovery It is also important to realize that non‑SAA is the major
of Hb was 153 (60–320) days, absolute neutrophil group of patients who do extremely well with ATG
count (ANC) >500 was in 64 (30–150) days, therapy. Once this group is excluded, there is marked
ANC >1000 was in 110 (50–260) days and platelets variation in the results for the treatment of SAA with
recovered in 96 (50–160) days as shown in Table 3. ATG at different centers.[11,12] It has been seen that patient
with mild/moderate AA respond to immunosuppression
Relapse much better than those with SAA or VSAA.
One patient who had achieved PR at 150 days relapsed
on the 200th day. Due to the financial constraints, the Stanazol has been shown to be effective only in 38% of
patient was put on supportive treatment at present and non‑SAA in Indian patients with no responses in SAA
he is still alive and transfusion‑dependent. and VSAA.[13] The available Indian data on the use of
ATG in adults according to Agarwal et al.[11] showed 40%
Side Effects
response rates to ATG in SAA and no response in VSAA
No patient developed serum sickness. Gum hypertrophy
developed in 14 out of 16 (87%) patients. Hypertension
was experienced by 5 out of 16 (31%) patients, requiring Table 4: Side effects of ATG/CSA therapy (n=16)
short‑term antihypertensives. Laboratory evidence of Side effects Incidence (%)
renal dysfunction was recognized in 2 (12%) patients, Fever 11 (69)
which normalized after discontinuation of CSA. Febrile Gum hypertrophy 14 (88)
neutropenia was present in 11 (68%) patients, in which Hypertension 5 (31)
2 patients developed lobar pneumonia. One adult Altered creatinine 2 (12.5)
patient who never achieved transfusion independence Secondary malignancy 1 (6)
ATG=Antithymocyte globulin; CSA=Cyclosporine
developed AML after 8 months of treatment.[10] Side
effects profile is described in Table 4.
Table 5: Final outcome of all 16 patients in
DISCUSSION comparison to other studies
The present study cohort included consecutive patients Results Current Marsh Tichelli
study (%) et al.[20] (%) et al.[28] (%)
from a single center. All patients had SAA or VSAA.
Overall response 8 (50) 40 (74) 134 (70)
Patients with mild or moderate AA were excluded.
No response 8#,@ (50) 14 (26) 58 (30)
Although the present study may be criticized for the small Relapse 1 (6.2) 3 (6) 38 (20)
number of patients treated with ATG‑CSA, heterogeneity Mortality 1 (6.2) 2 (4) 44 (23)
of immunosuppressants used and of being from a single Secondary malignancy 1 (6.2) 0 7 (3)
center, yet it illustrates clearly the real life challenges of LFU@ 2 (12.4) 1 (1.8) 0
#
One patient who had no response developed AML at 8 months after therapy.
many hematology‑oncology centers in the developing @
2 patients LFU who not get the response. Mortality in a patient who develop
world. Only 18 patients out of 102 diagnosed as AA in AML. AML=Acute myeloid leukemia; LFU=Lost to follow‑up

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Patel, et al.: Acquired severe aplastic anemia treated with ATG and Cyclosporine
compared to which our study demonstrated response rates
50% in adults with SAA and 100% those with VSAA (but
only 1 patient had VSAA). According to pediatric data
of Chandra et al.[14] response to ATG was 50%, which is
similar to our study. We compared our study with different
international studies as shown in Table 5.
Our study revealed an overall response rate of 50%
which is low as compared to two other studies by Marsh
et al.[15] (74%) and Tichelli et al.[16] (70%). This may
be due small number of patients in the study population
and variation in a response rates (between 40% and
70%).[5] It could be hypothesized that the mechanism
of development of AA may be different in different
patients and there may be an intrinsic stem cell defect
rather than an autoimmune etiology.[17]
The 6.2% mortality (1/16) in the study cohort is
similar to patients using androgens and lower than
stanazol (22% mortality) within 2 months of starting
therapy. [13] Another Indian series reported 100%
mortality in nonresponders to ATG.[11] Unhygienic
living conditions led to increased morbidity in Indian
patients. Because of improved supportive care, better
control of infections and the use of leukocyte‑depleted
blood products, patients can be kept alive during
prolonged periods of pancytopenia before and after
treatment with IST.[18,19] This also allows for the delayed
recovery of BM function and salvage treatment with
thesecond course of IST. Initial mortality can be reduced
with early diagnosis, early referral, and better care.
Patients being LFU is also a major issue, as in our study,
1 patient (5.5%) was LFU after getting treatment and
2 (28.7%) were lost after not getting a response. This
is because of poverty, lack of education, and logistics
related to long distance.
All the patients who responded revealed an improvement
in at least one cell line within 3 months and continued
to evolve into CR till the end of 1st year. 3 months
thus may be a reasonable checkpoint to consider
salvage treatment or alternative treatment strategies
as compared to the 4 months as earlier suggested.[10,20]
Relapses were seen in SAA patients after attaining
PR. It was seen in 1 patient who relapsed after a first
course. Over half of such patients may respond again.
Unlike most of the published series, in our study,
only 1 patient (6.2%) relapsed compared to Tichelli
et al.[16] where the relapse rate was 20%, possibly due to
prolonged duration of CSA therapy and slow tapering.
In a study from the European Group for BMT group,
10‑year cumulative risk of secondary malignancy
was 18.8% in AA patients treated with IST,[21] while
Journal of Applied Hematology
another study reported an incidence of 25%. The risk
was particularly high in patients treated with a repeat
course of IST.[21,22] In our study, only 1 patient (6.2%)
who did not respond to IST developed AML after
8 months, which is low compared to a study by Tichelli
et al. (20%). Clinically, apparent adverse effects of CSA
were mild, but the drug causes subclinical organ toxicity
and is expensive.[10,23] We therefore, recommend tapering
and finally discontinuing CSA in patients with stable
remissions for 12 months so as to avoid early relapse.
Favorable early results of the treatment with ATG,
methylprednisolone, and CSA have been confirmed in
several small series and large trials.[2‑15,17-19,24-27] ATG and
combination of CSA are more effective than CSA alone.
AA may be particularly sensitive to CSA in children.[28]
This report demonstrates that IST is of therapeutic
benefit to half of the adult and pediatric aplastic anemia
patients. Although CR was seen in 30% in adults and
33% in pediatric cases, but overall 50% cases were able to
enjoy transfusion‑independent life, requiring no further
treatment and no treatment associated adverse effects.
CONCLUSION
SAA is very difficult to manage without the availability
of BMT and in the presence of limited resources. ATG
is a hope with reasonable response ATG rates in view
of the fact that BMT is not available for every patient.
Financial Support and Sponsorship
Nil.
Conflicts of Interest
There are no conflicts of interest.
REFERENCES
1. Frickhofen N, Kaltwasser JP, Schrezenmeier H, Raghavachar A,
Vogt HG, Herrmann F, et al.Treatment of aplastic anemia with
antilymphocyte globulin and methylprednisolone with or without
cyclosporine. The German aplastic anemia study group. N Engl
J Med 1991;324:1297-304.
2. Rosenfeld SJ, Kimball J, Vining D, Young NS. Intensive
immunosuppression with antithymocyte globulin and
cyclosporine as treatment for severe acquired aplastic anemia.
Blood 1995;85:3058‑65.
3. Champlin R, Ho W, Bayever E, Winston DJ, Lenarsky C, Feig SA,
et al. Treatment of aplastic anemia: results with bone marrow
transplantation, antithymocyte globulin, and a monoclonal anti‑T
cell antibody. Prog Clin Biol Res 1984;148:227‑38.
4. Camitta B, O’Reilly RJ, Sensenbrenner L, Rappeport J,
Champlin R, Doney K, et al. Antithoracic duct lymphocyte globulin
therapy of severe aplastic anemia. Blood 1983;62:883‑8.
5. Bacigalupo A, Brand R, Oneto R, Bruno B, Socié G, Passweg J,
et al. Treatment of acquired severe aplastic anemia: Bone
marrow transplantation compared with immunosuppressive
therapy – The European Group for Blood and Marrow
Transplantation experience. Semin Hematol 2000;37:69‑80.
6. Frickhofen N, Kaltwasser JP, Schrezenmeier H, Raghavachar A,
Vogt HG, Herrmann F, et al. Treatment of aplastic anemia with
antilymphocyte globulin and methylprednisolone with or without
56 Vol. 6 • Issue 2 • April-June 2015
[Downloaded free from http://www.jahjournal.org on Wednesday, August 30, 2017, IP: 112.215.154.18]
Patel, et al.: Acquired severe aplastic anemia treated with ATG and Cyclosporine
cyclosporine. The German Aplastic Anemia Study Group. N Engl
J Med 1991;324:1297‑304.
7. Camitta BM, Thomas ED, Nathan DG, Santos G,
Gordon‑Smith EC, Gale RP, et al. Severe aplastic anemia: a
prospective study of the effect of early marrow transplantation
on acute mortality. Blood 1976;48:63‑70.
8. Frickhofen N, Heimpel H, Kaltwasser JP, Schrezenmeier H,
German Aplastic Anemia Study Group. Antithymocyte
globulin with or without cyclosporin A: 11‑year follow‑up of a
randomized trial comparing treatments of aplastic anemia. Blood
2003;101:1236‑42.
9. Miller AB, Hoogstraten B, Staquet M, Winkler A. Reporting
results of cancer treatment. Cancer 1981;47:207‑14.
10. Naithani R, Chandra J, Sharma S. Acute myeloid leukemia after
intensive immunosuppressive therapy in aplastic anemia. Indian
Pediatr 2005;42:939‑42.
11. Agarwal MB, Agarwal UM, Bhave AB, Vishwanathan C.
Anti‑lymphocyte globulin therapy in acquired aplastic anaemia.
J Assoc Physicians India 1993;41:371‑3.
12. Bacigalupo A, Hows J, Gluckman E, Nissen C, Marsh J, Van
Lint MT, et al. Bone marrow transplantation (BMT) versus
immunosuppression for the treatment of severe aplastic
anaemia (SAA): a report of the EBMT SAA working party. Br J
Haematol 1988;70:177‑82.
13. Marwaha RK, Bansal D, Trehan A, Varma N. Androgens in
childhood acquired aplastic anaemia in Chandigarh, India. Trop
Doct 2004;34:149‑52.
14. Chandra J, Naithani R, Ravi R, Singh V, Narayan S, Sharma S,
et al. Antithymocyte globulin and cyclosporin in children with
acquired aplastic anemia. Indian J Pediatr 2008;75:229‑33.
15. Saracco P, Quarello P, Iori AP, Zecca M, Longoni D, Svahn J,
et al. Cyclosporin A response and dependence in children
with acquired aplastic anaemia: a multicentre retrospective
study with long‑term observation follow‑up. Br J Haematol
2008;140:197‑205.
16. Schrezenmeier H. Treatment of Aplasticanemia with
Immunosuppressin and Hematopoient Growth Factors:
25th Annual EBMT Meeting Eductional Book. Hamburg,
Germany; 1998. p. 123‑31.
17. Tichelli A. Immunosuppressive therapy in aplasticanemia. Blood
2011;117:4433.
18. Bacigalupo A, Bruno B, Saracco P, Di Bona E, Locasciulli A,
Locatelli F, et al. Antilymphocyte globulin, cyclosporine,
prednisolone, and granulocyte colony‑stimulating factor for
severe aplastic anemia: An update of the GITMO/EBMT
study on 100 patients. European Group for Blood and
Marrow Transplantation (EBMT) Working Party on Severe
Aplastic Anemia and the Gruppo Italiano Trapianti di Midolio
Osseo (GITMO). Blood 2000;95:1931‑4.
Vol. 6 • Issue 2 • April-June 2015
19. Gluckman E, Esperou‑Bourdeau H, Baruchel A, Boogaerts M,
Briere J, Donadio D, et al. Multicenter randomized study comparing
cyclosporine‑A alone and antithymocyte globulin with prednisone
for treatment of severe aplastic anemia. Blood 1992;79:2540‑6.
20. Gupta V, Gordon‑Smith EC, Cook G, Parker A, Duguid JK,
Wilson KM, et al. A  third course of anti‑thymocyte globulin in
aplastic anaemia is only beneficial in previous responders. Br J
Haematol 2005;129:110‑7.
21. Tichelli A, Passweg J, Nissen C, Bargetzi M, Hoffmann T,
Wodnar‑Filipowicz A, et al. Repeated treatment with horse
antilymphocyte globulin for severe aplastic anaemia. Br J
Haematol 1998;100:393‑400.
22. Di Bona E, Rodeghiero F, Bruno B, Gabbas A, Foa P,
Locasciulli A, et al. Rabbit antithymocyte globulin (r‑ATG) plus
cyclosporine and granulocyte colony stimulating factor is an
effective treatment for aplastic anaemia patients unresponsive to
a first course of intensive immunosuppressive therapy. Gruppo
Italiano Trapianto di Midollo Osseo (GITMO) Br J Haematol
1999;107:330‑4.
23. Schrezenmeier H, Hinterberger W, Hows J, Ljungman P,
Locasciulli A, Marin P, et al. For the EBMT SAAWorking party
second immunosuppressive treatment of patients with aplastic
anemia not responding to the first course of immunosuppression:
A report from the working party on severe aplastic anemia of the
EBMT. Bone Marrow Transplantation 1995;15 Suppl. 1: S10.
24. Socié G, Henry‑Amar M, Bacigalupo A, Hows J, Tichelli A,
Ljungman P, et al. Malignant tumors occurring after treatment of
aplastic anemia. European Bone Marrow Transplantation‑Severe
Aplastic Anaemia Working Party. N Engl J Med 1993;329:1152‑7.
25. Marsh J, Schrezenmeier H, Marin P, Ilhan O, Ljungman P,
McCann S, et al. Prospective randomized multicenter study
comparing cyclosporin alone versus the combination of
antithymocyte globulin and cyclosporin for treatment of patients
with nonsevere aplastic anemia: a report from the European
Blood and Marrow Transplant (EBMT) Severe Aplastic Anaemia
Working Party. Blood 1999;93:2191‑5.
26. Reghavachar A, Kolbe K, Hoffken K. Standard
immunosuppression is superior to cyclosporine/filgrastim in
severe aplasticanemia: the German Multicemter Study [abstract].
Bone Marrow Transplant 1999;23 Suppl 1:S31.
27. Kojima S, Hibi S, Kosaka Y, Yamamoto M, Tsuchida M,
Mugishima H, et al. Immunosuppressive therapy using
antithymocyte globulin, cyclosporine, and danazol with or
without human granulocyte colony‑stimulating factor in children
with acquired aplastic anemia. Blood 2000;96:2049‑54.
28. Fogarty PF, Yamaguchi H, Wiestner A, Baerlocher GM,
Sloand E, Zeng WS, et al. Late presentation of dyskeratosis
congenita as apparently acquired aplastic anaemia due to
mutations in telomerase RNA. Lancet 2003;362:1628‑30.
57 Journal of Applied Hematology