Antithymocyte globulin and cyclosporine for severe aplastic anemia: association between hematologic response and long-term outcome

Context  In most patients, aplastic anemia results from T-cell–mediated immune destruction of bone marrow. Aplastic anemia can be effectively treated by stem cell transplantation or immunosuppression. Objective  To assess long-term outcomes after immunosuppressive therapy. Design, Setting, and Patients  Cohort of 122 patients (31 were 18 years and 91 were >18 years) with severe aplastic anemia, as determined by bone marrow cellularity and blood cell count criteria, were enrolled in a single-arm interventional research protocol from 1991 to 1998 at a federal government research hospital. Interventions  A dose of 40 mg/kg per day of antithymocyte globulin administered for 4 days, 10 to 12 mg/kg per day of cyclosporine for 6 months (adjusted for blood levels), and a short course of corticosteroids (1 mg/d of methylprednisolone for about 2 weeks). Main Outcome Measures  Survival, improvement of pancytopenia and transfusion-independence, relapse, and evolution to other hematologic diseases. Results  Response rates were 60% at 3 months after initiation of treatment, 61% at 6 months, and 58% at 1 year. The blood cell counts of patients who responded no longer satisfied severity criteria and they were transfusion-independent. Overall actuarial survival at 7 years was 55%. Survival was associated with early satisfaction of response criteria (86% vs 40% at 5 years; P<.001) and by blood counts at 3 months (reticulocyte count or platelet count of >50 x 10³/µL predicted survival at 5 years of 90% [64/71] vs 42% [12/34] for patients with less robust recovery [P<.001 by log-rank test]). There were no deaths among responders more than 3 years after treatment. Relapse was common, but severe pancytopenia usually did not recur. Relapse did not influence survival. Thirteen patients showed evolution to other hematologic diseases, including monosomy 7. Conclusions  Approximately half of patients with severe aplastic anemia treated with antithymocyte globulin and cyclosporine have durable recovery and excellent long-term survival. These outcomes were related to the quality of hematologic recovery.      

Treatment of severe aplastic anemia by immunosuppressor anti-lymphocyte globulin/anti-thymus globulin as the chief medicine in combination with Chinese drugs

Objective:To study the therapeutic effect of combined therapy with Chinese drugs and immunosuppressors, mainly anti-lymphocyte globulin/anti-thymus globulin(ALG/ATG),for the treatment of severe aplastic anemia(SAA),the efficacy associated factors and adverse effects as well.Methods:A retrospective analysis was conducted on 65 patients with SAA treated by combined therapy which was supplemented with cyclosporin A,androgen,hematopoietic growth factor,etc.Results:Of the 57 patients followed-up,26 (45.6%) we...     

抗淋巴细胞球蛋白联合环孢菌素A治疗重型再生障碍性贫血

目的:观察抗淋巴细胞球蛋白(ALG)和环孢菌素A(CsA)联合治疗重型再生障碍性贫血(SAA)的疗效. 方法: SAA患者13例,联合使用ALG 10 mg/(kg·d)静脉输注,1～5 d;CsA 3～5 mg/(kg·d)口服,31 d开始使用,疗程3 mo,根据血清肌酐及胆红素浓度调节剂量. 结果: 目前存活患者10例,死亡3例. 治疗1 mo内即有血液学反应,脱离红细胞以及血小板输注的中位时间分别为52 d和44 d. 治疗3 mo血象可以满足基本生活需要. 在治疗期间有少量并发症发生. 结论: ALG联合CsA治疗SAA疗效明显.     

抗淋巴细胞球蛋白联合环孢素A治疗重型再生障碍性贫血

目的:观察抗淋巴细胞球蛋白(ALG)和环孢素A(CsA)、雄激素联合治疗重型再生障碍性贫血(SAA)的疗效.方法:对43倒SAA患者联合使用CsA5 mg/(kg·d)剂量,服用6个月、雄激素和ALG治疗按15mg/(kg·d)的剂量,加入0.9%氯化钠注射液1000 ml中静滴,每日1次,每次维持10 h,连用5 d.结果:治疗6个月后,患者的各项血细胞计数明显上升(P＜0.01).基本治愈6例,缓解18例,明显进步8倒,无效5例,死亡3倒,转化为阵发性睡眠性血红蛋白尿2例,总有效率74.4%.环孢素A不良反应:11例肝功能受损,6例肾功能受损,4例牙龈增生,1例多毛症;ALG不良反应:2例血清病,1例脑出血死亡.结论:ALG联合环孢素A、雄激素治疗SAA疗效明显.     

丙种球蛋白联合环孢素、雄激素治疗重型再生障碍性贫血

目的探讨进一步提高重型再生障碍性贫血(SAA)疗效的方法。方法对我院1998年1月至2004年6月采用雄激素基础上大剂量丙种球蛋白(HDIG)联合环孢霉素A(CsA)治疗SAA8例进行疗效及早期感染率观察。结果CsA联合HDIG及雄激素治疗SAA有效率为75%,早期感染率(治疗3月内)为37.5%。结论该方案治疗SAA能提高疗效,且安全、简便。     

Analysis of the prognostic factors of very severe aplastic anemia treated with Chinese Kidney-invigorating drugs in combination with anti-lymphocyte globulin or anti-thymocyte globulin

<正>Objective:To explore the prognostic factors for very severe aplastic anemia(VSAA) patients treated mainly with Chinese Kidney(Shen)-invigorating drugs(CKID) combined with anti-lymphocyte globulin (ALG) or anti-thymocyte globulin(ATG).Methods:Twenty-seven VSAA patients were treated with CSID+ALG/ ATG therapy in conjunction with cyclosporine A,androgen,hemopoietic growth factor,etc.The relationship of the effectiveness and some factors(age of patients,course of illness,blood and bone marrow figures, etc.) were analyzed.Results:In the 25 evaluated VSAA patients who had been followed up for over 1 year,9 patients(36.0%) were basically cured,5(20.0%) remitted,6(24.0%) were markedly improved,and 5(20.0%) were treated in vain,with the total effective rate of treatment being 80.0%(20/25).Better clinical therapeutic effects were shown in patients newly diagnosed with VSAA,of male sex(P=0.037),20 years old(P=0.045), with an illness course≤1 month(P=0.048),with peripheral neutrophil count0.1×10~9/L(P=0.023),and with reticulocyte count10×10~9/L(P=0.002).Platelet count(P=0.620) and bone marrow lymphocyte percentage (P=0.736) showed no correlation with the therapeutic effectiveness.Multi-factor analysis by the Kaplan-Meier procedure on the factors influencing survival showed that rather longer survival times occurred in patients20 years old,with peripheral neutrophil count≤0.1×10~9/L,reticulocyte count10×10~9/L,and platelet count10×10~9/L(all P=0.0001).Bone marrow lymphocyte percentage and the initiation time of ALG/ATG application (from onset of the illness) showed no significant influence on patients' survival time(P=0.085 and P=0.935, respectively).Conclusions:CSKD+ALG/ATG therapy for treatment of VSAA could enhance the current clinical therapeutic effects and elevate patients' survival rate.Conditions including male sex,age20 years,illness course1 month,neutrophil count0.1×10~9/L,and reticulocyte count10×10~9/L are the likely effective indices for predicting favorable therapeutic effectiveness in newly diagnosed VSAA patients.     

以FCA预处理的造血干细胞移植治疗SAA的临床研究

目的 探讨以氟达拉滨(Flu)、低剂量环磷酰胺(CTX)和抗胸腺细胞球蛋白(ATG)为预处理的FCA方案异基因造血干细胞移植治疗重型再生障碍性贫血(SAA)的疗效及安全性.方法 用FCA预处理方案预处理移植治疗SAA-Ⅰ型和SAA -Ⅱ型患者各2例,其中同胞供者人类白细胞抗原(HLA)低分辨配型(6/6位点)全相合的骨髓联合外周血造血干细胞移植3例、非血缘关系高分辨HLA配型(10/10位点)全相合的外周血造血干细胞移植1例.同胞供者的预处理方案:Flu 30 mg·m-2d-1×5 d,CTX 50～60 mg· kg-1d-1×5 d,ATG 3 mg·kg-1d-1×3 d.非血缘关系的预处理方案:CTX 20 mg· kg-1d-1×2 d,ATG 5 mg· kg-1d-1 ×3 d,Flu 30 mg· m-2d-1 ×4 d.移植物抗宿主病(GVHD)的预防:均采用低剂量环孢素A(CsA)联合低剂量短程甲氨蝶呤(MTX),非血缘关系移植加用霉酚酸酯(MMF)0.5 g bid,+1 d～+28 d.观察移植并发症、输血量、造血重建、嵌合体和生存状态.结果 4例患者均获得造血干细胞的成功植入,移植后中性粒细胞绝对值(ANC)＞0.5×109/L的时间为+10 d～+15 d,血小板(PLT) ＞20× 109/L的时间为+10 d ～ +20 d,移植后输注红细胞3～6 U,血小板4～10 U,随访7～42个月,完全供者嵌合体,血液学完全缓解;患者1出现广泛型慢性移植物抗宿主病(cGVHD),死于多脏器功能衰竭,其余3例无病生存,其中非血缘关系移植的患者4发生轻度局限型cGVHD和巨细胞病毒血症,经过治疗很快控制.结论 Flu、低剂量CTX和ATG的FCA预处理方案的异基因造血干细胞移植治疗SAA的疗效肯定,患者耐受性好,值得推广.     

ATG联合环孢素A治疗重型再生障碍性贫血近期疗效分析

目的：分析抗人胸腺球蛋白(ATG)联合环孢素A(CsA)治疗重型再生障碍性贫血(SAA)患者的近期疗效以及不良反应,为SAA的治疗提供依据。方法：选择2009年12月-2011年5月于本中心接受ATG联合CsA治疗的SAA患者15例,观察治疗后患者临床表现的改善、外周血象的变化及用药期间不良反应的发生率等情况。结果：15例患者中,达到疗效评估时间者共10例,其中完全缓解4 例(40.0%),部分缓解4 例(40.0%),无效1例(10.0%),死亡1例(10.0%),近期总有效率为80.0%。患者血象在ATG治疗后1~2个月开始逐渐改善,首先出现白细胞及中性粒细胞的回升,血红蛋白及血小板在治疗3个月后开始稳定并回升。用药后最常见的不良反应为急性过敏反应及血清病反应（53%）,其次为感染（40%）。结论：对于不能行造血干细胞移植的SAA患者,ATG联合CsA是标准治疗方案,疗效满意。     

抗胸腺球蛋白联合环孢素A治疗儿童重型再生障碍性贫血9例分析

目的探讨联合使用抗胸腺球蛋白（ATG）及环孢素A（CSA）治疗儿童重型再生障碍性贫血（SAA）的疗效及影响因素。方法应用ATG联合CSA治疗9例儿童SAA。ATG4—5mg／（kg·d）静脉滴注,CSA起始量为3-5mg!（kg·d）,辅以成分血输注、造血生长因子等支持治疗。检测治疗前后外周血象及骨髓象的变化,以流式细胞仪测定治疗前后外周血T淋巴细胞亚群的改变情况。结果随访9例中基本治愈3例,缓解3例,明显进步2例,死亡1例,总有效率为88．89％。治疗后3个月外周血CD4＋细胞比例升高,CD8＋细胞比例降低,CD4＋／CD8＋比值升高,与治疗前比较差异有统计学意义（P〈0．01）。结论联合使用ATG、CSA作为初诊儿童SAA的首次治疗方案效果良好。     

中西医结合治疗重型再生障碍性贫血26例

目的：观察多种药物联合治疗重型再生障碍性贫血的疗效及中西医结合治疗重型再生障碍性贫血的效果。方法：联合应用抗淋巴细胞球蛋白和环孢素及中药治疗重型再生障碍性贫血,从患者临床表现及血常规、骨髓象变化观察治疗效果。结果：治疗总有效率达89%,显著高于单用环孢素或抗淋巴细胞球蛋白治疗,且取得临床缓解的时间明显缩短。结论：中西医结合方法治疗再生障碍性贫血有较好的疗效。     

Aplastic anemia associated with dyskeratosis congenita treated with antilymphocyte globulin and cyclosporine: a case report

Dyskeratosis congenita (DC) is a severe inherited disease characterized by a triad of clinical manifestations including abnormal skin pigmentation, nail dystrophy, and mucosal leukoplakia.^1 Bone marrow failure is the principal cause of early mortality, together with an increased predisposition to malignancy and fatal pulmonary complications.     

山莨菪碱与康力龙联合治疗再生障碍性贫血的疗效观察

目的:探讨山莨菪碱与蛋白同化剂(康力龙)联合治疗再生障碍性贫血的疗效。方法:125例再生障碍性贫血患者分为2组,治疗组用山莨菪碱和康力龙联合治疗,对照组用康力龙治疗。结果:治疗组与对照组相比较,疗效差异有统计学意义(P<0.05)。结论:山莨菪碱治疗再生障碍性贫血有较好疗效,且无明显毒副作用,方法简单,价格低廉,值得临床进一步推广应用。     

Treatment of severe aplastic anemia: comparison of bone marrow transplantation to immunotherapy

Between February 1985 and May 1988, sixteen patients with severe aplastic anemia (SAA) post multitransfusion were treated with either allogeneic bone marrow transplantation (BMT) (9) or immunosuppression (7). The latter group was further divided into two subgroups: horse anti-human thymocyte-lymphocyte globulin (ATG-ALG) (2) and high dose methylprednisolone (HDMP) (5). There were 8 males and 8 females, age ranged from 10 to 35 years for the BMT group and 19 to 56 for the immunosuppression group. As of analysis, 9 patients in the BMT group had been followed from 1 to 31 months after transplant (median,24). Graft rejection was noted in 2, both had positive mixed lymphocyte culture (MLC) index. Seven had full recovery of hematopoiesis. Of these 7 survivals, none developed acute graft-versus-host disease (GVHD), whereas 2 had chronic GVHD which resolved completely after a 9-month treatment with azathioprine and prednisolone. Kaplan-Meier survival probability at 31 month was 75%. In the immunosuppressive therapy group 2, who received ATG-ALG both failed the treatment, died 7 and 29 months later, respectively. There were 3 responders in the HDMP subgroup, 1 complete, 2 partial. The 1-year survival probability for this group was 42.9% compared with 75% in the BMT group (p greater than 0.10). However, the hematologic reconstitution and Karnofsky performance were complete in all 7 transplant survivals vs one of 3 in the immunosuppression group (p less than 0.01). This experience supports that for patients with SAA under the age of 40, BMT is the treatment of choice if an HLA-identical MLC-nonreactive marrow donor is available, if not, immunosuppression is an alternative approach.(ABSTRACT TRUNCATED AT 250 WORDS)     

重组人白细胞介素-11治疗重型再生障碍性贫血血小板减少的临床观察

目的  观察重组人白介素-11（rhIL-11）治疗重型再生障碍性贫血（SAA）患者血小板减少的疗效和安全性。方法  选取2005年6月-2014年12月该院SAA住院患者30例,所有患者接受猪抗人淋巴细胞球蛋白（p-ALG）治疗。将有无应用rhIL-11患者分为治疗组和对照组。治疗组所有患者在p-ALG治疗后给予rhIL-11治疗。用法为rhIL-11 3 mg,皮下注射,1次/d。当血小板计数（PLT）<10×109/L时,输注单采血小板。监测血常规并观察记录患者用药后的不良反应及单采血小板输注量。结果  两组PLT由最低恢复至≥20×109/L的时间分别为（43.43±11.78）和（53.42±10.80）d,差异有统计学意义（t =-2.672,P =0.012）;两组PLT由最低恢复至≥100×109/L的时间分别为（72.43±16.97）和（86.85±10.73）d,差异有统计学意义（t =-2.734,P = 0.011）;两组在PLT恢复至≥20×109/L时,输注血小板悬液的数量分别为（5.81±2.17）和（8.00±2.29）u,差异有统计学意义（t =-2.688,P =0.012）。主要不良反应为水肿、注射部位疼痛、结膜充血、乏力、发热等,无Ⅳ度不良反应,不良反应都较轻,可以耐受。结论  SAA血小板减少患者应用rhIL-11可促进血小板增生,加快血小板恢复,减少血小板输注量,从而减少出血等并发症的发生,节约费用,提高治疗的效果。其不良反应较轻,患者可耐受,值得推广应用。

     

血美安胶囊治疗再生障碍性贫血临床分析

目的：探讨血美安胶囊对再生障碍性贫血的临床疗效。方法：采用前瞻性随机对照方法,观察血美安胶囊加康力龙联合治疗38例再生障碍性贫血患者血红蛋白,白细胞,血小板上升变化情况。结果：血美安胶囊联合治疗组总有效率86．84％,明显高于基础治疗组（有效率仅为53．5％）,两组对比有较明显差异（P＜0．05）,结论：;血美安胶囊是治疗再生障碍性贫血安全,廉价,效果满意的药物。     

造血生长因子对成人再生障碍性贫血伴严重感染患者的疗效分析

目的 探讨对成人再生障碍性贫血伴严重感染患者实施造血生长因子治疗的效果。方法 随机将2018年1月～2019年7月我院62例再生障碍性贫血伴严重感染患者分为对照组（31例,应用免疫抑制治疗）和观察组（31例,在对照组治疗基础上应用造血生长因子治疗）。对比两组治疗总有效率、症状缓解时间、T淋巴细胞亚群（CD3+、CD4+、CD8+、CD4+/CD8+值）水平及不良反应总发生率。结果 观察组治疗总有效率（93.55%）高于对照组（74.19%）,差异有统计学意义（P＜0.05）;观察组体温恢复时间、咳痰消失时间、肺部啰音消失时间均较对照组更短,差异有统计学意义（P＜0.05）;观察组治疗后CD3+、CD8+较对照组更低,CD4+、CD4+/CD8+值较对照组更高,差异有统计学意义（P＜0.05）;观察组不良反应总发生率和对照组比较,差异无统计学意义（P＞0.05）。结论 对成人再生障碍性贫血伴严重感染患者实施造血生长因子治疗有助于增加T淋巴细胞免疫力,对病情恢复具有较好促进作用。     

扶正养营汤对免疫介导再生障碍性贫血小鼠的治疗作用

目的：观察扶正养营汤对免疫介导再生障碍性贫血（再障）小鼠骨髓增殖及外周血IL-2水平的影响。方法：采用完全随机数字表法将制作的免疫介导再障小鼠(BALB/c)模型40只分为4组,另用10只同批正常小鼠设为正常对照组(E组)。采用盲法分别胃饲生理盐水(A组及E组)、扶正养营汤(B组)、环孢霉素A (C组)、扶正养营汤+环孢霉素A (D组)共10d。检测各组小鼠外周血象、骨髓有核细胞计数、测定各组骨髓造血组织容量及外周血IL-2水平。结果：A组小鼠外周血象、骨髓有核细胞数、造血组织容量显著低于E组(P<0.05);B,C,D组较A组增加(P<0.05),尤以D组最为明显(P<0.05);而B组与C组比较差异无统计学意义(P>0.05)。A组小鼠外周血IL-2水平明显高于E组(P<0.05);B,C,D组低于A组(P<0.05);D组低于B组及C组(P<0.05);B组与C组比较差异无统计学意义(P>0.05)。结论：扶正养营汤具有促进免疫介导再障小鼠骨髓增殖,降低其外周血IL-2水平的作用。     

环孢素A联合康力龙治疗慢性再生障碍性贫血的疗效观察

目的探讨环孢素A联合康力龙治疗慢性再生障碍性贫血的疗效。方法选择2016年12月～2017年12月我院收治的慢性再生障碍性贫血患者60例,将其随机分为观察组和对照组,每组各30例,对照组予环孢素A治疗,观察组同时联合康力龙,治疗后对两组的临床疗效进行评价,同时检测两组患者治疗前后白细胞、血小板、血红蛋白的水平。结果观察组患者治疗后基本治愈12例、缓解10例,总有效率达73.3%,显著高于对照组的总有效率50.0%,差异有显著性(P0.05)。治疗前,两组患者的白细胞、血小板、血红蛋白水平比较,差异无显著性(P0.05)。治疗后,两组患者的白细胞、血小板、血红蛋白水平分别较治疗前比较显著升高,且观察组患者治疗后的白细胞(4.72±0.36)×10~9/L,血小板(35.04±4.65)×10~9/L,血红蛋白(94.93±14.25)g/L,分别显著高于对照组,差异具有显著性(P0.05)。结论环孢素A联合康力龙治疗慢性再生障碍性贫血可以显著提高临床疗效,改善贫血等临床症状,提高患者的生活质量,值得临床推广和应用。     

单倍体亲缘异基因造血干细胞移植治疗SAA1例

目的探讨单倍体亲缘异基因造血干细胞移植治疗重型再生障碍性贫血(SAA)的可行性。方法对1例诊断SAA 4年余,先后经Cs A治疗、脐血移植治疗均无效并反复输注红细胞、血小板的12岁男性患者进行单倍体亲缘异基因造血干细胞移植,供者为其胞兄,高分辨HLA基因型5/10相合,预处理方案为BU+CTX+ATG:BU3.2 mg/kg×2 d,CTX 50 mg/kg×4 d,ATG 2.5 mg/kg×4 d。干细胞来源为G-CSF动员的骨髓+外周造血干细胞,共计输注单个核细胞(MNC)4.055×108/kg(受者体重),CD 34 2.331×106/kg。GVHD预防:-1 d采用与受者HLA部分相合的第三方脐带血细胞,术后联合应用环孢素A、短程氨甲碟呤、霉酚酸酯。结果造血缓慢重建,术后22天(+22 d)ANC>0.5×109/L,术后3月血小板脱离输注。+26天DNA指纹图全部表现为供者基因型。+40天血型转为供者型"O"型。+29 d出现急性移植物抗宿主病a GVHD(胃肠型,Ⅲ度),+31 d、+34 d及+42 d予巴利昔单抗20 mg静滴,+40 d、+44 d、+63 d输注间充质干细胞,患者急性GVHD逐渐控制。期间曾出现肺部感染、口腔黏膜炎及巨细胞病毒血症,经抗感染后可控制。现随访3年,血象正常稳定,Kamofsky评分100分。结论单倍体亲缘异基因造血干细胞移植治疗SAA,对无相合供者(包括亲缘或非亲缘)且强效免疫抑制治疗失败的患者,可考虑进行,GVHD和感染为主要并发症,需根据患者病情采用相应措施。