Immunosuppressive therapy with horse anti-thymocyte globulin and cyclosporine as treatment for fulminant aplastic anemia in children

Patients with severe aplastic anemia (SAA) and an absolute neutrophil count (ANC) of 0 typically have fatal outcomes. We defined fulminant AA (FAA) as ANC?=?0 for at least 2 weeks prior to and after immunosuppressive therapy (IST). We analyzed the outcomes of 35 children with FAA among 288 children who enrolled in a prospective study for AA (AA-97 study). AA was classified as FAA (n?=?35), very SAA (vSAA; n?=?129), or SAA (n?=?124). All of the children received the IST with horse anti-thymocyte globulin (ATG) and cyclosporine (CsA). A significantly lower response rate at 6 months was seen in children with FAA when compared to those with vSAA or SAA (40.0, 63.6, and 63.7 %, respectively; p?=?0.027). Of 20 nonresponder patients in the FAA group, 11 were rescued by alternative donor transplantation, and 5 patients showed a late response after 6 months. Consequently, no significant difference was noted in overall survival when comparing the FAA, vSAA, and SAA groups (88.5, 95.8, and 96.8 %). These findings indicate that IST with ATG and CsA is justified as a first-line treatment for children with FAA who lack a human leukocyte antigen-matched sibling donor.     

Intensive immunosuppression with antithymocyte globulin and cyclosporine as treatment for severe acquired aplastic anemia

Immunosuppressive therapy can produce hematologic improvement in a large proportion of patients with severe aplastic anemia. Antithymocyte globulin (ATG) is the current treatment of choice for patients who do not have histocompatible sibling donors or who are otherwise inegligible for allogeneic bone marrow transplantation. About 50% of patients respond to an initial course of ATG, and many nonresponders can be salvaged by subsequent treatment with cyclosporine (CsA). To determine whether simultaneous administration of these agents could further improve response rates, we enrolled 55 patients in a therapeutic trial of 4 days of ATG and 6 months of CsA. Among the 51 patients who had not received previous courses of ATG or CsA, 67% had responded by 3 months, and 78% had responded by 1 year (response was defined as an increase in peripheral blood counts sufficient that a patient no longer met the criteria for severe disease). There was a high incidence of relapse (36% actuarial risk at 2 years), but most relapsed patients responded to additional courses of immunosuppression, and relapse was not associated with a significant survival disadvantage. Evolution to myelodysplastic syndromes and acute leukemia was rare (1 of 51 patients), but the later appearance of paroxysmal nocturnal hemoglobinuria was more common (5 of 51 patients). Actuarial survival was 86% at 1 year and 72% at 2 years. These data support the use of a combination immunosuppressive regimen containing both ATG and CsA as first-line therapy for severe aplastic anemia.     

再生障碍性贫血免疫抑制治疗后阵发性睡眠性血红蛋白尿症克隆的演变及临床意义

目的 探索再生障碍性贫血(AA)免疫抑制治疗(IST)后阵发性睡眠性血红蛋白尿症(PNH)克隆变化情况及其临床意义.方法 将2008年1月至2012年2月收治的186例AA患者纳入本研究,其中55例重型AA(SAA)予抗胸腺细胞球蛋白(ATG)联合环孢素A(CsA)治疗,131例非重型AA(NSAA)予CsA治疗.治疗前所有患者进行PNH克隆筛查,治疗后进行随访.中位随访时间22(18 ～76)个月.结果 SAA组10例(18.9％)患者出现PNH克隆,NSAA组9例(7.4％)出现PNH克隆,前者出现PNH克隆比例高于后者(t=5.041,P=0.025),治疗后SAA组在6、12、18、＞24个月时PNH克隆规模大于NSAA组(13.38％比5.67％、14.88％比5.31％、20.00％比5.47％、18.85％比9.08％,P值均＜0.05).PNH克隆对2种IST方案疗效影响的差异无统计学意义.结论 AA患者予ATG联合CsA或CsA治疗后,均可出现PNH克隆,SAA患者ATG治疗后更明显.IST前后伴PNH克隆不影响IST疗效.     

中性粒细胞为0的成人重型再生障碍性贫血强化免疫抑制治疗研究

目的评价兔抗人胸腺细胞免疫球蛋白(anti-thymocyte globulin,ATG)联合环孢素A(cyclosporine,CsA)强化免疫抑制治疗(intensive immunosuppressive therapy,IIST)中性粒细胞为0的成人再生障碍性贫血的疗效。方法回顾性分析2014年1月至2018年3月国内三家医院86例接受IIST的重型再生障碍性贫血(severe aplastic anemia,SAA)临床资料。将免疫抑制治疗前中性粒细胞为0的SAA定义为暴发型再生障碍性贫血(fulminant aplastic anemia,FAA),与SAA、极重型再生障碍性贫血(very SAA,vSAA)比较对IIST的疗效。结果 86例患者中,FAA 19例,vSAA 23例,SAA 44例。3个月总有效率分别为21.1%,56.5%和54.5%,6个月总有效率分别为42.1%,60.9%和72.7%。FAA组患者3个月的有效率明显低于vSAA和SAA组(21.1%vs. 56.5%,P=0.032;21.1%vs. 54.5%,P=0.023),6个月的有效率明显低于SAA组(42.1%vs. 72.7%,P=0.028),疗效与中性粒细胞计数显著相关(P=0.019)。三组的中位起效时间分别为17.0个月,4.0个月和3.0个月,FAA组慢于vSAA组、SAA组(P=0.031,P=0.001)。FAA组患者总生存率明显低于vSAA和SAA组(63.2%, 91.3%和95.5%,P=0.001),生存率与中性粒细胞计数及疗效显著相关(P=0.026,P=0.010)。结论中性粒细胞为0的成人FAA临床预后严重不良,需要探索新的治疗方案。     

Treatment of severe aplastic anaemia with combined immunosuppression: anti-thymocyte globulin, ciclosporin and mycophenolate mofetil

Severe aplastic anaemia (SAA) can be successfully treated with immunosuppressive therapies or haematopoietic stem cell transplantation (HSCT). Response rates with horse anti-thymocyte globulin (h-ATG) plus ciclosporin (CsA) are about 60-70%, and robust responders have an excellent long-term survival. We introduced a third immunosuppressive agent to standard h-ATG/CsA, mycophenolate mofetil (MMF), in an attempt to improve the response rate and survival, and to decrease the relapse rate and clonal evolution to myelodysplasia. A total of 104 consecutive patients with SAA were treated with h-ATG/CsA/MMF between May 1999 and June 2003 at the National Institutes of Health Clinical Center. The overall response rate at 6 months was 62%, with 24 (37% of responders) patients relapsing at a median of 389 d from ATG. Nine patients showed evidence of clonal evolution following ATG. After a median follow up of 42 months, the median survival among responders was not reached and among non-responders was 58 months. Over half of the relapses occurred during MMF administration. Despite a strong theoretical rationale for its use, MMF did not result in the improvement of response or relapse rates when compared with historical standard h-ATG/CsA.     

Is the early cyclosporine A level predictive of the outcome of immunosuppressive therapy in severe aplastic anemia?

Immunosuppressive therapy (IST) has provided an alternative treatment option for cure of aplastic anemia patients who cannot receive bone marrow transplantation. Although there have been many recent studies on the efficacy of antithymoglobulin (ATG) combined with cyclosporine A (CsA), there is no data on the correlation between the variability of CsA levels and the response to IST. Therefore, we retrospectively assessed the factors associated with IST efficacy in patients with acquired severe aplastic anemia (SAA). Sixty‐six patients were treated with ATG combined with CsA for 6 months. In the response group, the CsA levels were increased rapidly to more than 200 ng/mL within the first 2 wk after starting the IST. However, the non‐response group had a pattern of slower increase of the CsA levels. The CsA levels, during the first and second week of treatment with IST, were significantly different in the responders and non‐responders. The factors predictive of response to IST and survival were analyzed. The univariate analysis showed that a younger age at the initiation of IST, a high absolute neutrophil count prior to starting IST, a short interval between the diagnosis and initiation of IST, and high CsA levels during the first and second week of IST treatment were positively associated with the response rate and overall survival. The multivariate analysis showed that these four factors were independent factors associated with a longer patient survival. A high response rate was associated with a short interval between diagnosis and initiation of IST as well as high CsA levels during the first and second week of IST. Therefore, early intensification of CsA levels might improve patient outcome.     

Treatment of adults with severe aplastic anemia: primary therapy with antithymocyte globulin (ATG) and rescue of ATG failures with bone marrow transplantation.

PURPOSE: To evaluate a policy of immunosuppression with antithymocyte globulin (ATG) as primary therapy for adults with severe aplastic anemia (SAA) regardless of the availability of an HLA-identical bone marrow donor. PATIENTS AND METHODS: Thirty-one consecutive adults with SAA who satisfied the age criteria for allogeneic bone marrow transplantation (BMT) (age less than 51 years) were treated with ATG 20 mg/kg/day for 10 days along with high-dose corticosteroids. Patients with an HLA-identical donor received a transplant if they did not respond to ATG or if they developed life-threatening complications during or soon after ATG administration. Eight patients with no response to ATG were also treated with oral cyclosporine 12.5 mg/kg/day. RESULTS: Eleven patients had a complete and five a partial response to ATG; two patients improved with cyclosporine treatment, resulting in an overall response rate of 58% to immunosuppression. Nine of 14 patients with donors received a BMT: seven because they did not respond to ATG and two because of serious infections. Seven grafts were obtained from related and two from unrelated donors. There was no significant difference in survival between those with and without a related HLA-identical donor (log-rank p value = 0.969). At a median follow-up of 58 months, 26 of 31 are alive with an actuarial survival of 80% at 5 years. Two patients died of infection, two died from complications of BMT, and one remains transfusion-dependent. One patient died of refractory leukemia at 30 months; one patient relapsed with hypoplasia 95 months after initial therapy with ATG. He showed a complete response to treatment with cyclosporine. No other late hematologic events have occurred. CONCLUSIONS: This treatment approach resulted in the restoration of hematopoiesis and independence from transfusion in 80% of patients with SAA entered into the study. The efficacy of allogeneic BMT in salvaging cases in which ATG failed does not appear to be compromised. Follow-up for the development of clonal hematologic disorders remains an important part of this treatment policy.     

Horse antithymocyte globulin as salvage therapy after rabbit antithymocyte globulin for severe aplastic anemia

The effectiveness of salvage therapy for aplastic anemia patients unresponsive to initial rabbit antithymocyte globulin (r‐ATG) or cyclophosphamide is not known. We investigated the administration of standard horse ATG (h‐ATG) plus cyclosporine (CsA) in patients who were refractory to initial r‐ATG/CsA (n = 19) or cyclophosphamide/CsA (n = 6) (registered at clinicaltrials.gov as NCT00944749). The primary endpoint was hematologic response at 3 months and was defined as no longer meeting the criteria for severe aplastic anemia. Of the 19 patients who received r‐ATG as initial therapy, 4 (21%) achieved a hematologic response by 3 months, and of the 6 patients who received cyclophosphamide, only 1 (17%) responded by 6 months. Among the responders there were no cases of relapse, and in nonresponders 2 patients evolved to monosomy 7. The overall survival for the cohort at 3 years was 68% (95% CI, 50–91%). These results suggest that only a minority can be successfully salvaged after receiving as first therapy either r‐ATG or cyclophosphamide. Although h‐ATG may be utilized in the salvage setting, the overall response rate probably will be lower than when h‐ATG is used as initial treatment. Am. J. Hematol. 89:467–469, 2014. © Published 2014.     

Restoration of immunity and reactivation of hepatitis B virus after immunosuppressive therapy in a patient with severe aplastic anaemia

We recently treated a patient with severe aplastic anaemia (SAA) who also had chronic hepatitis B virus (HBV) infection. The HBV serological status at the time of diagnosis of SAA was HBsAg(+) and HBeAg(+). Subsequent analysis of the precore region of HBV DNA showed wild-type. He received anti-thymocyte globulin (ATG) and cyclosporin A (CsA) therapy twice. After each course of ATG infusion and during CsA therapy he developed lymphopenia for 1 and 2.5 months, respectively. His serum alanine aminotransferase (ALT) became normalized during the period of lymphopenia, but the serum HBV viral load increased. When his peripheral lymphocytes count recovered, his ALT became elevated again. Lamivudine was effective to normalize his elevated ALT and suppress viral replication. The phenomenon observed in this case supports the prevailing notion that hepatitis B flare-up in HBV carriers after chemotherapy is caused by an immune-mediated mechanism. Meanwhile, this is the first documented case of SAA who developed HBV reactivation upon recovery of lymphopenia after immunosuppressive therapy. This also highlights the necessity of pre-emptive therapy with lamivudine in SAA/HBsAg(+) patients to receive immunosuppressive therapy with ATG/CsA.     

ATG加CsA方案治疗重型再生障碍性贫血临床研究

目的:探讨ATG加CsA方案治疗重型再生障碍性贫血(再障)的疗效、疗程和治疗相关并发症.方法:对56例重型再障给予ATG加CsA方案治疗,每月至少观察一次血常规、肝、肾功能等项目.结果:56例中完全反应45例(80％),部分反应5例(9％),无效6例(11％).复发10例(20％).结论:ATG加CsA治疗重型再障疗效...     

Predictors of early mortality after rabbit antithymocyte globulin as first-line treatment in severe aplastic anemia

Despite being recommended as first-line immunosuppressive therapy in severe aplastic anemia (SAA), horse antithymocyte globulin (ATG) is still unavailable in many countries outside the USA. Rabbit ATG is more lymphocytoxic than horse ATG, and this might result in a higher incidence of severe infections and early mortality. This study was designed to identify the risk factors for early mortality and overall survival (OS) after rabbit ATG in patients with SAA. We retrospectively reviewed 185 patients with SAA who underwent rabbit ATG and cyclosporine. The incidence of death in 3 months following rabbit ATG therapy was 15.1% (28/185). Early mortality was mainly related to infectious complications, despite adequate antibiotic and/or antifungal treatment. Age > 35 years (odds ratio [OR] 5.06, P = 0.001) and baseline absolute neutrophil count (ANC) ≤ 0.1 × 10⁹/L (OR 7.64, P < 0.001) were independent risk factors for early mortality after immunosuppressive therapy with this agent. Hematological response at 6 months was observed in only 29.7% of all patients. OS at 1 year after rabbit ATG was 75.3%; and age > 35 years (OR 1.88, P = 0.03), baseline ANC ≤ 0.1 × 10⁹/L (OR 2.65, P < 0.001), and lack of response to rabbit ATG (OR 11.40, P < 0.001) were independently associated with mortality. Alternative strategies are needed for the treatment of SAA patients in countries were horse ATG is unavailable, particularly for those at high risk for early mortality after rabbit ATG due to a higher age and very low pre-treatment neutrophil count.     

环孢霉素A联合脐血血浆治疗重型再生障碍性贫血的探讨

目的：探讨进一步提高重型再生障碍性贫血（SAA）疗效的方法。方法：采用环孢霉素A（CsA)联合脐血血浆（CBP）治疗SAA13例,并与CsA加细胞因子治疗组进行疗效比较。结果：CsA联合CBP治疗SAA总有效率为69．2％,与CsA加细胞因子治疗组疗效（60．0％）相近（P＞0．05）。结论：CsA联合CPB是安全、方便的治疗SAA的有效方案。     

Results at a single centre of immunosuppression with cyclosporine A in 66 children with aplastic anaemia

A retrospective analysis of cyclosporine A (CsA) monotherapy administered to 66 children with aplastic anaemia (AA) at a single centre was carried out. The study was conducted on 66 children (F34/M32) with a median age of 10.5 years. 30 children (45%) achieved complete or partial remission within a median of 8 weeks. The response rate was 3/19 (16%) in cases of very severe aplastic anaemia (vSAA), 16/34 (47%) in severe aplastic anaemia (SAA) and 11/13 (85%) in nonSAA. 10 remitters (33%) relapsed after CsA cessation or dose tapering and six of those responded again on CsA alone. The only variable predictive for response was granulocyte count before treatment. The actuarial probability of survival was 51% at 4 years (85% in moderate AA, 50% in SAA and 32% in vSAA). The optimal dosage of CsA has yet to be established.     

Severe aplastic anemia with autoimmune thyroiditis showing no hematological response to intensive immunosuppressive therapy

A 39-year-old woman with severe aplastic anemia (SAA) was transferred to our institution. She also had autoimmune thyroiditis with several positive autoantibodies. Clonal or oligoclonal T-cell proliferation was demonstrated by determining the size distribution of the complementarity-determining region 3 (CDR3) of T-cell receptor beta-chain (TCR-Vbeta) subfamilies in the patient's bone marrow and peripheral blood cells. The results suggested that hematopoiesis was suppressed by immune-mediated mechanisms. Immunosuppressive therapy for SAA using cyclosporin A (CsA) alone or concurrent CsA and antithymocyte globulin (ATG) failed to induce a hematological response. The intensity of the autoantibodies, however, partially decreased during this period. In addition, the CD4/CD8 ratio was inverted after immunosuppressive therapy. These observations indicate that, in a subset of SAA, immune-mediated hematopoietic suppression cannot be successfully treated by conventional immunosuppressive therapy, even though a substantial improvement in the underlying immunological changes can be achieved. Other therapies such as hematopoietic stem cell transplantation or more intensified repeated ATG therapy may be necessary for such patients.     

Retreatment with rabbit anti-thymocyte globulin and ciclosporin for patients with relapsed or refractory severe aplastic anaemia

The management of patients with severe aplastic anaemia (SAA) who do not have a matched sibling donor and fail a course of horse anti-thymocyte globulin (h-ATG)/ciclosporin (CsA) is uncertain. Repeated courses of ATG-based immunosuppression are often employed; in children and increasingly in adults, alternative donor haematopoietic stem cell transplantation is an option. We analysed the success rate of retreatment with rabbit ATG (r-ATG)/CsA in 43 patients treated at our institution in the last 5 years; 22 were refractory (20 adults; two children) to h-ATG/CsA-based regimens and 21 (17 adults; four children) had relapsed after h-ATG/CsA-based regimens. The overall response rate was 30% in patients who were refractory to h-ATG and 65% in patients who had relapsed following h-ATG. The 1000-d survival in patients who responded to r-ATG was 90% compared with 65% in non-responders. Six patients developed a clonal haematological disorder; two were responders, two were non-responders and in two the evolution occurred before the response could be assessed at 3 months following r-ATG. Thirteen patients died; three were responders, six were non-responders and four patients died prior to 3 months when response was assessed. In our study, the response rate in refractory patients was inferior to what has been previously reported.     

Antithymocyte globulin and cyclosporine for treatment of 44 children with hepatitis associated aplastic anemia

We analyzed the outcomes of 44 children with hepatitis associated aplastic anemia (HAA) who received immunosuppressive therapy (IST) with antithymocyte globulin (ATG) and cyclosporine (CsA). Fourteen (31.8%) patients achieved complete response and 17 (38.6%) achieved partial response, for an overall response rate of 70.4% after 6 months. Seven non-responders received bone marrow transplantation from an HLA-matched unrelated donor and 6 out of 7 are alive. The probability of overall survival at 10 years was 88.3+/-4.9%, which supports the role of IST with ATG and CsA as treatment of choice for children with HAA without an HLA identical sibling donor.     

Immunosuppressive therapy for acquired severe aplastic anemia (SAA): a prospective comparison of four different regimens

OBJECTIVE: This study was designed to investigate four different immunosuppressive therapy (IST) regimens as treatment of acquired severe aplastic anemia (SAA). PATIENTS AND METHODS: 142 consecutive SAA patients were randomized to receive one of the following IST regimens: equine anti-human thymocyte immunoglobulin (E-ATG) alone (IST regimen I); E-ATG and cyclosporine A (CSA) (IST regimen II); E-ATG, CSA plus recombinant human granulocyte-macrophage colony-stimulating factor (rhuGM-CSF) and rhu erythropoietin (rhuEPO) (IST regimen III); or rabbit ATG (ATG-F), CSA, rhuGM-CSF, and rhuEPO (IST regimen IV). No repeated courses of E-ATG or ATG-F were given for nonresponders. All patients also received stanozolol or testosteron propionate. RESULTS: The overall response rate to IST regimen I was 58%. The response to IST regimen II (79%) was significantly higher (p = 0.04), more rapid and complete than after IST regimen I. The response rate to IST regimen IV (53%) was significantly lower than that of IST regimen III (73%, p = 0.039). The additional use of growth factors did not reduce early deaths and did not accelerate hematopoietic recovery after IST. Of the 142 patients enrolled in this trial, 92 (65%) are alive at a median follow-up time of 102 months (range, 54-166 months). The 5-year actuarial survival for IST regimens I, II, III, and IV was 58%, 81%, 80%, and 66%, respectively. CONCLUSION: The combination of E-ATG and CSA remains the best combination for the treatment of SAA patients, producing a survival advantage at 5 years. The addition of growth factors did not improve these results. Rabbit ATG-F appeared less effective than E-ATG.     

Treatment of severe aplastic anemia with antithymocyte globulin and cyclosporin A with or without G-CSF in adults: a multicenter randomized study in Japan

We report the results of a randomized study to elucidate whether addition of granulocyte colony-stimulating factor (G-CSF) to immunosuppressive therapy is valuable for the treatment of severe aplastic anemia (SAA) in adults. A total of 101 previously untreated patients (median age, 54 years; range, 19 to 75 years) were randomized to receive antithymocyte globulin (ATG) and cyclosporin A (CyA) (G-CSF- group) or ATG, CyA, and G-CSF (G-CSF+ group). In the G-CSF+ group, the hematologic response rate at 6 months was higher (77% vs 57%; P = .03) than in the G-CSF- group. No differences were observed between the groups in terms of the incidence of infections and febrile episodes. There were no differences between the G-CSF- group and the G-CSF+ group in terms of survival (88% vs 94% at 4 years), and the development of myelodysplastic syndrome (MDS)/acute leukemia (AL) (1 patient vs 2 patients). However, the relapse rate was lower in the G-CSF+ group compared with the G-CSF- group (42% vs 15% at 4 years; P = .01). Further follow-up is required to elucidate the role of G-CSF in immunosuppressive therapy for adult SAA.     

Long‐term follow‐up study of porcine anti‐human thymocyte immunoglobulin therapy combined with cyclosporine for severe aplastic anemia

Immunosuppressive therapy with antithymocyte immunoglobulin (ATG) and cyclosporine A is the first treatment option for severe aplastic anemia (SAA) patients without transplantation. Horse ATG is not marketed in China. Because the price of porcine ATG (pATG) is only about one‐third of the price of rabbit ATG (rATG), long‐term follow‐up studies of pATG's efficacy will help provide valuable insights into the treatment of SAA. Retrospective studies were performed to analyze the clinical information of 102 SAA patients treated with pATG and cyclosporine A from 1999 to 2014 in Peking Union Medical College Hospital. The median age was 29 years old (range 12–72). Median follow‐up time was 59.6 months (0.2–176.8). The overall response rate was 74.5% (CR 42.1%, PR 32.4%). The recurrence rate was 9.9%. The mortality rate was 16.7%. The median survival time has not been reached, and the 5‐year survival rate was 81.8%. Other hematologic abnormalities were observed in 7.8% of patients, including symptomatic PNH, MDS, and AML. Multivariate analysis revealed there was no significant effect on survival by factors such as gender, age, severity of disease, treatment time, and PNH clone (P > 0.05). These data have indicated pATG therapy combined with cyclosporine A has significant long‐term efficacy and high overall survival in SAA.     

Rabbit-antithymocyte globulin combined with cyclosporin A as a first-line therapy: improved, effective, and safe for children with acquired severe aplastic anemia

Purpose

Acquired aplastic anemia is an organ-specific auto-immune disease characterized by pancytopenia and hypoplastic bone marrow. Immunosuppression with anti-thymocyte globulin (ATG) and cyclosporine A (CsA) is an effective and safe therapy for patients without undergoing hematopoietic stem cell transplantation. The aim of the current study was to investigate the effect of rabbit-ATG (r-ATG) combined with CsA as an intensive immunosuppressive therapy (IST) for acquired severe aplastic anemia (SAA) in children.

Methods

From January 2003 to November 2008, 46 children (30 boys and 16 girls), with a median age of 7?years (between 2 and 15?years) were diagnosed with acquired SAA. They received an IST of r-ATG combined with CsA. The average time was 3.4?months (ranging from 1 to 13?months). The effective rates 3, 6, 9, and 12?months after treatment were 30.4, 65.2, 78.8, and 84.8%, respectively. After 2?years of follow-up, the response rate was 84.8% (39/46). No response was found in five cases and relapse was found in two.

Results

Among the five cases without response, two received unrelated hematopoietic stem cell transplantation and are already disease-free and two died from infection caused by long-term dependence on infusion. No myelodysplastic syndrome or acute myeloid leukemia was found among the patients.

Conclusions

We propose that r-ATG combined with CsA as an intensive IST is effective and safe in treating acquired SAA in children.