Complete response to tacrolimus in a child with severe aplastic anemia resistant to cyclosporin A

Aplastic anemia (AA) is a rare disorder in children, usually treated with immunosuppressive therapy (IST) including antithymocyte globulin (ATG) and cyclosporin A. There are no current widely used alternative therapies with comparable efficacy. We describe a child with severe aplastic anemia (SAA), who developed severe gingival hyperplasia secondary to cyclosporin A, unresponsive to intensive dental intervention. When IST was changed to tacrolimus there was a significant improvement in the gingival hyperplasia, but equally important, he achieved complete response of his AA within several months. The use of tacrolimus in children with AA may be a potential modality of treatment. Pediatr Blood Cancer 2009;52:525–527. © 2008 Wiley‐Liss, Inc.     

免疫抑制治疗对儿童重型再生障碍性贫血 细胞因子表达的影响

目的 探讨重型再生障碍性贫血(AA)患儿经免疫抑制治疗（IST）后外周血相关细胞因子表达水平的变化。方法 纳入2017年10月至2018年12月在首都医科大学附属北京儿童医院（我院）住院初诊为获得性重型AA（SAA）/极重型AA（VSAA）且应用IST治疗的患儿为SAA/VSAA组，同期在我院住院初诊为获得性非重型AA（MAA）并给予环孢素A(CsA)口服治疗的患儿为MAA组。采用流式细胞术检测两组患儿初诊时、SAA/VSAA组治疗6个月和12个月、MAA组治疗6个月外周血中IFN-γ、TNF-α、IL-2、IL-4、IL-6和IL-10的表达水平。结果 SAA/VSAA组25例，MAA组37例。①初诊时SAA/VSAA组IFN-γ和IL-6表达较MAA组增加（P<0.05）。②SAA/VSAA组经IST治疗1年后，IFN-γ和IL-6较治疗前明显降低，差异均有统计学意义(P<0.05)。③截至末次随访，SAA/VSAA组除3例失访外，余22例全部生存，无复发。结论 SAA/VSAA患儿血清细胞因子水平异常，IST可显著改善初治患儿相关造血负向调控因子的表达。     

多种免疫抑制剂联合治疗儿童重型再生障碍性贫血

同时应用环胞菌素，抗胸腺细胞球蛋白，大剂量免疫球蛋白和大剂量甲工泼尼松龙等免疫抑制剂对１７例小儿ＳＡＡ（１０例ＳＡＡ－Ｉ，７例ＳＡＡ－Ⅱ）进行联合免疫抑制治疗。结果３例基本治愈，７例缓 解，３例明显进步，总有效率达７６．５％。（１３／１７例）。     

Immunosuppressive Therapy in Aplastic Anemia

Objective

To assess the response to antithymocyte globulin based immunosuppressive therapy (IST) in pediatric patients with idiopathic aplastic anemia.

Methods

Thirty patients (19 boys and 11 girls) with aplastic anemia received antithymocyte globulin and cyclosporine. Twenty-two patients had severe and 8 had very severe aplastic anemia.

Results

Mean age of the patients was 9.19?±?2.56?y. Three patients died within 1?mo of therapy, two due to sepsis and one due to intracranial hemorrhage. Twenty-seven patients were analyzed for response to therapy. Eight patients (29.7%) responded at 3?mo: 3 complete response (CR) and 5 partial response (PR). Six mo after the therapy, overall response (OR) was seen in 9/27 (33.3%), with one more patient in no response group achieving partial response. At 1?year, patients in CR maintained their status and 1 patient in PR group relapsed. He again achieved partial response with repeat course of ATG. Responders had significantly shorter duration of illness and higher absolute neutrophil count as compared to non responders to IST. None of the patients developed acute leukemia in the follow up.

Conclusions

The treatment of aplastic anemia in pediatric patients is a challenging task. One third of the patients achieved overall response which included both complete and partial response.     

抗胸腺细胞球蛋白治疗儿童再生障碍性贫血的临床研究

目的 总结以抗胸腺细胞球蛋白(ATG)为主的免疫抑制疗法治疗儿童再生障碍性贫血时,ATG的实施方法、不良反应防治和长期随访措施等与远期疗效的相关性.方法 儿童再生障碍性贫血35例,其中极重型再生障碍性贫血(VSAA)6例,急性再生障碍性贫血(SAA)11例,慢性重型SAA8例,中型再生障碍性贫血(MAA)10例.ATG治疗期间措施包括:治疗前清除感染灶;积极防治过敏反应;密切观察和处理因ATG相关血小板减少所致严重出血和免疫抑制所致严重感染;积极防治血清病;重视长期随访中的治疗措施与质量.结果 ATG治疗后,所有病例均出现60%以上的淋巴细胞绝对计数下降.平均随访28个月,总有效率为77.14%(27/35),显效率为57.14%(20/35).VSAA、SAA和MAA间疗效无明显差异.ATG不良反应观察结果:①48.6%出现轻度类过敏反应;②血清病发生率42.9%,平均病程3.6 d;③9例(25.7%)外周血小板(BPC)计数＜10×109/L;④8例(22.9%)在ATG治疗后1个月内发生感染;⑤未发生ATG治疗相关死亡.Genzyme和Fresenius两种不同ATG制剂,在疗效和ATG相关不良反应发生率方面差异均无统计学意义.结论 ATG治疗儿童SAA和MAA疗效显著,但需积极预防和控制ATG不良反应,避免治疗相关死亡.长期辅助治疗和提高随访质量,也是确保疗效的重要环节.

Abstract：

Objective To evaluate the efficacy of antithymocyte globulin (ATG) based immunosupression therapy for childhood aplastic anemia, to reduce the adverse effects and to observe the long-term outcome. Method Thirty-five children with aplastic anemia (AA) were enrolled in this study.Six of the cases had very severe AA (VSAA), 11 had severe AA (SAA)-Ⅰ, 8 had SAA-Ⅱ and 10 had moderate AA (MAA). All these patients were treated with ATG plus Cyclosporin A (CSA). The following measures were taken during the ATG therapy: infection of the patients had been controlled before ATG treatment. Comprehensive anti-allergic measures were implemented. Close attention was paid to the hemorrhage related with platelet reduction caused by ATG and severe infection of the patients. Result Shortly after the ATG usage, all the patients had a significant decrease of absolute peripheral lymphoblast count by more than 60 percent. With a mean follow-up time of 28 months, the total effective rate was 77.14％ ( 27/35), significant response rate was 57.14％(20/35). There was no significant difference among VSAA, SAA and MAA groups in the response rate. Adverse reactions included the following:① 48.6％ (17/35) patients presented mild anaphylactoid reaction during the first day of ATG treatment; ②42.9％(15/35) cases presented serum sickness 5-11 days after the last dose of ATG with a mean duration of 3. 6 days, all the patients were cured effectively with methylprednisolone; ③25.7％ (9/35)patient's peripheral blood platelet count was reduced, might be caused by ATG, to below 10 × 109/L, but no patient had severe hemorrhagic complication after platelet transfusion was performed; ④22.9％ ( 8/35 ) of patients got infection within a month after ATG therapy, including 3 cases with clinical septicemia, all the 3 cases recovered after antibiotics treatment. There was no ATG treatment-related death in this series. Conclusion ATG is a very effective therapy for children with SAA and MAA. Comprehensive measures are needed to prevent and handle the side effects to avoid treatment-related death. Long-term supportive therapy and proper follow up contribute to the favourable outcomes of the patients.     

环胞菌素A治疗儿童再生障碍性贫血疗效研究

探讨环胞菌素 A(CSA)治疗儿童再生障碍性贫血 (再障 )的方法 ,疗效和疗效相关因素。方法 :应用 CSA对 34例儿童再障行免疫抑制治疗 (IS) ;部分重型再障(SAA)加用抗胸腺细胞球蛋白 (ATG)或大剂量免疫球蛋白 (HDIG) ,均以雄性激素作为辅助治疗。结果 :基本治愈 4例 ,缓解 1 1例 ,明显进步 8例 ,总有效率为 6 7.6 5 % ;其中 2 9例 SAA总有效率为 6 5 .5 2 % ,1 8例慢性重型再障 (SAA- )有效率为5 5 .5 6 % ;1 1例急性再障 (SAA- )总有效率达 81 .82 % ,单项资料对比分析结果显示SAA的年龄 ,性别和治疗前外周血象等因素与 CSA有效率无关 ;但病程较短者 (<1 2个月 )有效率较高 ;CSA与 ATG等行联合 IS则有效率可明显提高。结论 :CSA为治疗儿童再障的有效方法之一 ,SAA拟选用联合 IS,雄性激素为 CSA的有效辅助治疗     

免疫抑制疗法治疗儿童再生障碍性贫血疗效分析

目的：探讨免疫抑制疗法(IST)治疗儿童再生障碍性贫血(AA)的疗效、安全性及影响疗效的主要因素。方法：对2007年1月至2010年12月接受IST治疗的55例重型再生障碍性贫血（SAA）及51例慢性再生障碍性贫血（CAA）患儿的临床资料进行回顾性分析。结果：① 在CAA患儿中,抗胸腺球蛋白（ATG）联合环孢素A（CsA）治疗组总有效率明显高于CsA单独治疗组(80％ vs 44％,P40%、治疗前无重症感染以及有G-CSF早期治疗反应的患儿治疗效果较好,而治疗效果与AA分型、年龄等指标无关。结论：ATG+CsA联合治疗是治疗儿童AA的一种安全有效的方法;病程长短、有无严重感染、骨髓造血面积及G-CSF早期治疗反应是影响疗效的主要因素。     

免疫抑制治疗儿童再生障碍性贫血疗效分析

目的探讨提高儿童再生障碍性贫血(再障,aplastic anemia,AA)疗效的治疗方法。方法回顾分析56例接受正规治疗且随访≥3个月的再障患儿的临床资料,56例按治疗方案分为2组,一组为单用环胞素A(CsA)治疗(A组),另一组抗胸腺细胞球蛋白(ATG)联合CsA免疫治疗(B组),比较两组患儿的疗效及生存率。结果 31例慢性再障(CAA)患儿中接受A组治疗30例,总体有效率为83.3%(25/30),仅1例CAA患儿接受B组治疗。25例重型再障(SAA)患儿接受B组治疗16例,治疗有效率为50.0%(8/16),较接受A组治疗的9例SAA患儿的有效率(44.4%)高,但差异无统计学意义(P>0.05)。接受B组治疗的16例SAA患儿,12个月生存率为66.7%,2年生存率70.0%。结论 ATG联合CsA免疫治疗是儿童再障,尤其是无合适供体进行造血干细胞移植的SAA患儿首选方案,但应注意足量、持续用药,并努力降低ATG治疗期间感染发生率,这对提高儿童SAA治愈率有重要意义。[临床儿科杂志,2012,30(5):428-430]     

Treatment of aplastic anemia with antithymocyte globulin,cyclosporin A,methylprednisolone, danazole and recombinant human granulocyte-colony stimulating factor

The main purpose of the present study was to determine the response rate to immunosuppressive therapy combined with recombinant human granulocyte-colony stimulating factor (rhG-CSF) and its efficacy for preventing infections in patients with severe aplastic anemia. The treatments included one course of antithymocyte globulin, cyclosporin A, methylprednisolone, danazole and rhG-CSF. Three patients had very severe aplastic anemia and two had moderate aplastic anemia. One patient relapsed 13 months following the first course of therapy and received a second course. Five patients received six courses of treatment and the response rate at 6 months was 83.3%. All patients achieved an absolute neutrophil count of greater than 1.0 × 10⁹/L within 40 days. All patients with a complete response are transfusion-free and doing well. All five patients are currently alive and have not had any episode of infection for 17–53 months. The results of the study indicate that this therapy may improve the poor prognosis of young patients with severe aplastic anemia. It has a good response rate and induces a rather rapid increase in the neutrophil count, which protects against life-threatening bacterial and fungal infections.     

兔抗人胸腺细胞免疫球蛋白治疗重型再生障碍性贫血25例疗效分析

目的探讨使用兔抗人胸腺细胞免疫球蛋白(ATG)治疗重型再生障碍性贫血(SAA)的疗效及毒副反应。方法回顾性分析2004-2009年共25例SAA患儿应用ATG+环孢素A+雄激素治疗后随访半年以上的疗效。观察患儿血象变化、远期克隆性改变、感染。结果 ATG治疗半年后25例患儿中17例(68%)有效,其中5例(20%)基本治愈,3例(12%)缓解,9例(36%)明显进步,8例(32%)无效中2例(8%)行异基因造血干细胞移植后治愈,2例(8%)半年后因感染死亡。随访期间1例SAA-II型发生远期克隆性改变转变为MDS。1例患儿在输注ATG过程中出现皮疹、发烧、关节痛;2例出现喉头水肿;输注后2周内患儿出现血清病反应,表现为皮疹、发热、关节痛。第1周7例,第2周1例。结论本组患儿用ATG+环孢素A+雄激素治疗有效率68%。毒副作用主要表现为发热、皮疹、关节痛,极少数出现喉头水肿,ATG使用过程中出现的过敏反应及使用后出现的血清病反应均可获得较好控制。     

儿童重型/超重型再生障碍性贫血免疫抑制治疗后克隆演变的临床特征分析

目的 探讨儿童重型/超重型再生障碍性贫血(SAA/VSAA)免疫抑制治疗(IST)后发生克隆演变患儿的临床特征及克隆演变发生的危险因素。方法 回顾性分析231例初诊并接受IST的SAA/VSAA患儿临床资料,统计IST后克隆演变的发生率,并分析克隆演变的危险因素。结果 231例患儿的5年总体生存率为82.7%,其中18例早期死亡,213例进行疗效评价。231例患儿初诊时14例(7.4%)检测到至少2个中期分裂象的染色体异常,95例患者外周血粒细胞或红细胞可检测到PNH克隆。213例进行疗效评价的患者中15例发生IST后克隆演变,其中包括MDS/AML和7号染色体缺失在内的不良克隆演变10例,以及PNH及+8染色体异常的良性克隆演变5例;IST后良性克隆演变与不良克隆演变的5年累积发生率为(2.2±2.2)%与(4.8±3.3)%;至末次随访,良性与不良克隆演变患儿分别100%(5/5)与50%(5/10)存活。初诊WBC3.5×10~9/L、CD~(3+)T细胞/淋巴细胞比值80%、抗胸腺细胞球蛋白每日剂量3.0 mg/kg及IST后6个月的治疗反应与不良克隆演变发生相关,其中CD~(3+)T细胞/淋巴细胞80%和IST后6个月的治疗无反应为独立影响因素。结论 SAA/VSAA患儿初诊淋巴细胞亚群CD~(3+)T细胞/淋巴细胞比值显著增高或IST早期反应不良与IST远期发生不良克隆演变相关,尽早识别发生不良克隆演变的高危患儿对于制定合理的诊疗决策至关重要。     

抗淋巴细胞球蛋白治疗再生障碍性贫血的疗效及不良反应

目的 探讨抗淋巴细胞球蛋白(ALG)治疗再生障碍性贫血(AA)的疗效.分析ALG不良反应的特点和防治方法.方法对2002年4月-2009年10月本院收治的162例诊断为AA并接受ALG治疗的患儿的临床资料进行回顾性分析,共154例完成了ALG 疗程.其中极重型AA(VSAA)34例,重型AAⅠ型(SAAⅠ)103例,重型AAⅡ型(SAAⅡ)7例,中型AA(MAA)10 例.结果 154例中,基本治愈62例(40.3%),缓解15例(9.7%),进步28例(18.2%),无效或死亡23例(14.9%),失访26例(16.9%),总有效率为68.2%,复发8例(5.2%).63例出现变态反应,主要表现为发热和皮疹等.发生时间为用药1～5 d,持续1～4 d.8例因严重变态反应而停止使用ALG,其中1例死于严重的全身血管性变态反应.81例出现血清病反应,主要表现为发热、皮疹和关节肿痛等.发生时间为ALG治疗结束2～14 d,持续1～12 d.有无血清病与ALG疗效差异无统计学意义(P>0.05).患儿性别、年龄、CD4/CD8、人白细胞Dr抗原与血清病发生率的差异均无统计学意义(Pa>0.05).结论 ALG治疗AA疗效肯定,变态反应和血清病为治疗中常见的不良反应,应用甲泼尼龙可较好地控制过敏和血清病症状.     

联合免疫抑制治疗儿童重型和难治型再生障碍性贫血

目的　本研究旨在探索联合免疫抑制 (CIS)治疗儿童重型再障 (SAA)和难治型再障 (RAA)的疗效 ,并进行有关疗效预测和临床方法学等方面的研究。方法　应用抗胸腺细胞球蛋白 /抗淋巴细胞球蛋白、环胞菌素A和大剂量免疫球蛋白 (HDIG)等对 36例儿童SAA(n =33)和RAA(n =3)进行CIS治疗 ,随访观察疗效 ,并将以往接受单一药物免疫抑制 (SIS)治疗的 4 3例病儿 (42例SAA ,1例RAA)作为疗效对照组。同时进行外周血淋巴细胞亚群和血清细胞因子等免疫功能指标检测 ,探索儿童再障的免疫介导致病机制及其与IS疗效的关系 ,并总结临床治疗方法与经验。结果　CIS治疗儿童再障 ,总有效率为 80 .6 % (2 9/36 ) ,其中SAA有效率和显效率分别达到 78.8% (2 6 /33)和 6 0 .6 % (2 0 /33) ,均明显高于以往SIS治疗对照组 [5 7.1% (2 4 /42 ) ,2 8.6 % (12 /42 ) ]。CIS治疗3例RAA均有效 ,而SIS治疗 1例RAA无效。儿童再障的主要异常指标为CD4 /CD8比例下降 ,IL 2R、IL 8和TNF表达增高 ,所有病例均存在 2项以上指标的明显异常。疗效预测研究显示 ,治疗前 ,病程短于 6个月或网织红细胞绝对计数高于 10× 10 9/L者 ,SIS治疗有效率显著增高 ,但上述因素与CIS疗效无关。由于采用较为合理的治疗方法和副反应防治措施 ,两组未出现明显的重要     

THE BENEFIT OF ATG IN IMMUNOSUPPRESSIVE THERAPY OF CHILDREN WITH MODERATE APLASTIC ANEMIA

Background. Previous studies specifically focused on the immunosuppressive therapy (IST) of children with moderate aplastic anemia (MAA) are rare. The aim of this study was to evaluate the advantage of using antithymocyte globulin (ATG) in the IST and its outcome of children with MAA. Methods. Forty-two children diagnosed with moderate aplastic anemia from 1993 to 2006 were retrospectively reviewed. Eighteen patients treated with ATG, cyclosporin A (CSA), and androgen are defined as the ATG group, the other 24 patients treated with CSA and androgen are defined as the non-ATG group. Survival and hematological response of the two groups were studied. Results. Response rate and transfusion-independent survival of the ATG group were both significantly higher than those of the non-ATG group (83.33 vs. 41.7%, p =. 006; and 83.33 vs. 50%, p =. 043, respectively). Compared with non-ATG group, fewer patients in ATG group progress to severe aplastic anemia (p =. 03). Conclusion. Immunosuppressive therapy including ATG benefits children with moderate aplastic anemia.     

ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION IS SUPERIOR TO IMMUNOSUPPRESSIVE THERAPY IN INDIAN CHILDREN WITH APLASTIC ANEMIA—A SINGLE-CENTER ANALYSIS OF 100 PATIENTS

The authors compared the outcome in 100 children (61 boys, 39 girls; median age of 10.1 ± 3.4 years) with aplastic anemia who underwent either immunosuppressive therapy (IST; n = 70) or hematopoietic stem cell transplantation (HSCT; n = 30) between 1998 and 2007. Conditioning regimes for HSCT were a combination of either cyclophosphamide (Cy) with antilymphocyte globulin (ALG) or fludarabine (Flu) with Cy or busulfan (Bu) ± antithymocyte globulin (ATG). Stem cell source was bone marrow in 20 and peripheral blood stem cells (PBSCs) in 10. Patients undergoing IST received either equine ALG or ATG in combination with steroids and cyclosporine. Primary engraftment was seen in 25 children (83.3%), with acute graft-versus-host disease (aGvHD) in 5 (16.6%). The day 100 transplant-related mortality (TRM) was 30% and at a median follow up of 36 months (range: 6–197), the overall and disease-free survival is 70%. Among children who received IST, 60 children received ALG while 10 received ATGAM. Responses were seen in 27 children (43.5%), which was complete (CR) in 12 and partial (PR) in 15. At a median follow up of 38 months (range: 1–84), the overall survival is 37.1%, with 81.4% survival among responders and <10% survival among non-responders. HSCT would be the treatment of choice in children with severe aplastic anemia who have a human leukocyte antigen (HLA)-matched related donor and is superior to IST in this series from India.     

Outcome of children with severe acquired aplastic anemia treated with rabbit antithymocyte globulin and cyclosporine A

ObjectiveTo evaluate the outcome of children with severe acquired aplastic anemia treated with rabbit antithymocyte globulin and cyclosporine as first-line treatment at this institution.MethodsRetrospective analysis of 26 pediatric patients with aplastic anemia, treated between 1996 and 2011 with rabbit antithymocyte globulin plus cyclosporine.ResultsThe overall response rate at six months was 34.6% (9/26), and the cumulative incidence of relapse was 26.5% (95% confidence interval [CI]: 1.4%-66%) at 5 years. The cumulative incidence of clonal evolution after immunosuppressive therapy was 8.3% (95% CI: 0.001%-53.7%) at five years with both clonal evolutions in non -responders who acquired monosomy 7 karyotype. The overall survival at five years was 73.6% (95% CI: 49.2%-87.5%).ConclusionsThe present results confirm the poor response rate with rabbit antithymocyte globulin as first therapy in pediatrics patients, similar to what has been reported for patients of all ages. This confirmation is problematic in Brazil, given the lack of horse antithymocyte globulin in many markets outside the United States.     

Immunosuppressive therapy versus bone marrow transplantation for children with aplastic anemia

A total of 15 patients 1 to 16 years of age were treated for aplastic anemia (13 of a severe degree) and followed-up for a mean of 24 months (range 2 to 64 months). Six patients had an HLA-matched sibling and underwent allogeneic bone marrow transplantation. Nine patients who lacked a suitable donor were given immunosuppressive therapy. Antithymocyte globulin was the initial treatment for eight of these nine patients. Two patients who failed to respond to antithymocyte globulin were then treated with cyclosporine A. Pretreatment age, hematologic measurements, duration of follow-up, and interval prior to therapy were similar between the two groups. All of the patients receiving bone marrow transplants had a complete response and now have normal blood cell counts. Six of nine patients (67%) responded to antithymocyte globulin and are now transfusion free, although three have mild thrombocytopenia. Both patients given cyclosporine A had a good response and are also transfusion free. Patients who underwent marrow transplantation had a significantly shorter period of transfusion dependence for RBCs (9 v 4 weeks, P less than .005) and platelets (5 v 21 weeks, P less than .05). The patients given immunosuppressive therapy have significantly lesser platelet counts in follow-up but have similar values for both hemoglobin and absolute granulocyte counts. Although HLA-matched bone marrow transplantation leads to a faster and more complete recovery for children with aplastic anemia, immunosuppressive therapy can provide a good outcome for children with this disorder.     

Screening for paroxysmal nocturnal hemoglobinuria (PNH) clone in Egyptian children with aplastic anemia

Aplastic anemia and paroxysmal nocturnal hemoglobinuria (PNH) are clinically related. In addition to their concurrent or sequential appearance in individual patients, PNH and aplastic anemia share several pathophysiologic features. The aim of the present study was to screen for PNH clone in Egyptian aplastic anemia pediatric patients before the initiation of any specific therapy and to evaluate the clinical status of studied patients 3-6 months after initiation of immunosuppressive therapy. We studied 11 pediatric patients with newly diagnosed acquired aplastic anemia and followed them up clinically for 3-6 months after initiation of immunosuppressive therapy. In addition to routine clinical and laboratory evaluation, sucrose lysis test and staining of bone marrow for CD59 were performed in all subjects. All studies cases had severe aplastic anemia (SAA) except one case which had very severe aplastic anemia (VSAA). Sucrose lysis test was negative in all studied cases. Presence of PNH clone (as evident by loss of normal staining of hematopoietic cells for CD59 = CD59 negative cells) was evident in four subjects. All cases with PNH clone were >6 years old and one of them developed splenic vein thrombosis. As regards the laboratory data WBC < or = 2.8 x 10(3)/mm3 and reticulocytes > or = 0.6 per cent were the most frequent factors associated with PNH clone found in all PNH subjects, but only in 28.6 per cent and 14.3 per cent respectively, of non-PNH subjects. Mortality rate was higher in non-PNH subjects (28.5 per cent) compared to 25 per cent of PNH subjects. We conclude that immunohistochemical staining of bone marrow sections is a sensitive tool to detect the emergence of PNH clone in aplastic anemia patients. Thrombotic complications should be anticipated in cases with aplastic anemia having a PNH clone.     

免疫抑制治疗儿童重型再生障碍性贫血54例疗效分析

目的 探讨免疫抑制治疗儿童重型再生障碍性贫血（severe aplasia anemia,SAA）的疗效。方法 回顾性分析我院1997年1月—2003年6月儿童重型再生障碍性贫血54例,应用环孢素A（cyclosporine,CSA）和抗胸腺细胞球蛋白（antithymie globlin,ATG）为主的免疫抑制治疗,其中应用CSA联合ATG治疗31例（称为CSA联合ATG组）,应用CSA治疗23例（称为CSA组）,比较两组的治疗有效率、复发率、不良反应和无病生存率。结果两组的分型和极重型患者资料具有可比性。CSA联合ATG组和CSA组起效时间平均分别为2．5个月和3．5个月,两组有效率分别为81％（25／31）和52％（12／23）（x^2=4．962,P〈0．05）。治疗有效者共37例,CSA联合ATG组和CSA组的复发率分别为8％（2／25）和50％（6／12）（xc^2=6．143,P〈0．05）。两组患者不良反应的发生率差异无统计学意义。所有患者随访至少1年,CSA联合ATG组和CSA组1年以上生存率分别为81％（25／31）和52％（12／23）;随访超过2年者共47例,CSA联合ATG组和CSA组2年以上生存率分别为74％（20／27）和50％（10／20）（P〈0．01）。结论免疫抑制治疗儿童重型再生障碍性贫血的疗效肯定,而CSA联合ATG治疗重型再生障碍性贫血的疗效更优于单用CSA。     

Comparison between bone marrow transplantation and antithymocyte globulin in treatment of young patients with severe aplastic anemia

Fifty-seven patients younger than 25 years with severe aplastic anemia underwent either bone marrow transplantation or antithymocyte globulin therapy (ATG) to ascertain which approach should be used in young patients. Thirty-five patients who had an HLA-identical sibling donor underwent bone marrow transplantation after conditioning with cyclophosphamide and low-dose total-body radiation. Twenty-two patients who did not have an HLA-identical donor received ATG. The 2-year actuarial survival of patients after transplant is 72% (95%, CI 64% to 80%), versus 45% (95%, CI 29% to 61%) in those given ATG therapy (P = 0.18). In those patients surviving 6 months after treatment, return of peripheral blood counts to normal values was more common in patients who received marrow transplant compared with those given ATG therapy (P less than 0.001). Furthermore, 24 of 26 transplant survivors had Karnofsky performance scores greater than 90%, compared with only five of 13 ATG survivors. These data suggest that bone marrow transplantation is the preferred therapy for severe aplastic anemia in young patients who have an HLA-identical sibling donor. ATG should be reversed for those young patients with severe aplastic anemia who do not have a histocompatible marrow donor.