老年重型再生障碍性贫血的治疗

免疫抑制治疗（IST）被推荐为60岁以上重型再生障碍性贫血(SAA)或极重型再生障碍性贫血(VSAA)的首选方 案,但该人群合并症较多,加之既往疗效欠佳,故应用并不广泛。目前老年SAA的治疗选择差异非常大,且其选择往 往不完全基于客观标准。年龄本身并不是老年SAA使用IST的限制性因素,如果老年患者一般状态良好,且合并症 指数评分较低,则可将此方案作为一线治疗方案;身体状态不佳或有严重合并症的患者,可予环孢素A单独或联合其 他药物治疗。此外,做好支持治疗对该人群的生存亦有很大影响。     

再生障碍性贫血的免疫抑制治疗现状

目前免疫抑制治疗已忧为再生障碍性贫血的主要治疗措施之一。抗淋巴细胞球蛋白／抗胸腺细胞球蛋白治疗使严重型再生障碍性贫血的预后大为改观，免疫抑制剂的序贯治疗及联合强化治疗使ＳＡＡ的疗效得到了进一步提高。近年来由于一些重组造血因子的不断涌现，ＡＬＧ／ＡＴＧ联合一些造血因子，如粒细胞集落刺激因子，粒细胞－巨噬细胞集落刺激因子等治疗ＡＡ，缩短了中性粒细胞的恢复时间，减少了感染率，使ＡＡ的疗效有进一步提高的趋     

重型再生障碍性贫血的治疗

重型再生障碍性贫血是一组由一个或多个因素引起的骨髓造血功能衰竭，其病死率很高。近年来由于免疫抑制疗法、造血干细胞移植等新治疗手段的开展，其预后得到很大改善。本文就其新近进展作一综述。     

免疫抑制联合脐血输注治疗重型再生障碍性贫血

目的 :评价采用免疫抑制联合脐血输注治疗重型再生障碍性贫血(severe aplastic anemia,SAA)的疗效。方法:分析2010年5月至2016年5月间我院收治的19例接受氟达拉滨、兔抗胸腺细胞球蛋白(anti-thymocyte globulin,ATG)和环孢素(cyclosporin A,Cs A)免疫抑制并联合脐带血输注患者的临床资料,统计造血恢复情况、治疗反应、治疗相关死亡率、总生存(overall survival,OS)率等。结果:中性粒细胞恢复的中位时间仅为22(13,36)d,血小板恢复的中位时间为180(48,217)d。6例患者有短暂性或持续性脐带血植入,有脐带血植入患者中位血小板恢复时间显著快于无脐带血植入的患者(46 d比206 d,P=0.006)。3个月内治疗相关死亡率仅为5.3%,12个月的累积反应率为88.7%±7.5%,其中完全缓解(complete remission,CR)率达72.2%±10.6%。预期2年和5年OS率分别为94.7%±5.1%和78.9%±15.0%。结论:免疫抑制联合脐血输注治疗SAA安全有效,脐带血输注可能加速免疫抑制治疗SAA患者的造血恢复,有助于降低早期死亡率,增加CR率,保证患者较高的OS率和良好的生活质量。     

大剂量五湖安治疗重型再生障碍性贫血

目的：研究观察大剂量环磷酰胺（ＨＤ－ＣＴＸ）治疗重型再生障碍性贫血（ＳＡＡ）的疗效。方法：６８例ＳＡＡ患者应用了短疗程ＨＤ－ＣＴＸ治疗,第１－４天剂量分别为８００,８００,１６００,１６００ｍｇ,静脉点滴,同时注意加强支持治疗,并进行了长期随访观察。结果：基本治愈及缓解者２６例（３８．２３％）,明显进步１１例（１６．１８％）,总有效率５４．４１％,且无近期及远期严重并发症发生。结论：大剂量环磷酰胺     

几种免疫抑制剂联合方案治疗重型再生障碍性贫血的疗效比较

重型再生障碍性贫血(ＳＡＡ)进展迅速,预后凶险,免疫功能紊乱在其发病机制中起重要作用[1]。近年发现联合运用免疫抑制剂(ＩＳ)可提高疗效,但组合方案及疗效报道不一[2,3]。我科以含抗胸腺细胞球蛋自(ＡＴＧ)、环胞霉素(ＣｓＡ)及大剂量甲基强的松龙(ＨＤＭＰ)方案,并用大剂量免疫球蛋白(ＨＤＩＶＩｇＧ)或重组人粒细胞集落刺激因子(ＧＣＳＦ)联合康力龙或达那唑治疗,比较不同联合方案的合理应用。现将结果报道如下。对象与方法1.对象:1995年12月～2000年1月住院的14例初诊患者,重型再生障碍性贫血Ⅰ型(ｓＡＡⅠ)5例,重型再生障碍性贫血Ⅱ型…     

大剂量环磷酰胺治疗重型再生障碍性贫血

概述再生障碍性贫血（aplastic anemia,AA）是以全血细胞减少、骨髓低增生为特点的造血衰竭综合征,临床主要表现为贫血、出血和感染。根据发病机制不同可分为先天性AA和获得性AA。先天性AA有Fanconi贫血、先天性角化不良、Shwachman-Dia-     

抗淋巴细胞球蛋白联合雄激素治疗重型再生障碍性贫血的临床研究

重型再生障碍性贫血（ＳＡＡ）患者在无相匹配人类白细胞抗原（ＨＬＡ）供髓者行异基因骨髓移植（ａｌｌｏＢＭＴ）时,抗淋巴细胞球蛋白（ＡＬＧ）／抗胸腺细胞球蛋白（ＡＴＧ）是首选治疗药物。我所从１９８７年１月至１９９７年６月,应用ＡＬＧ联合雄激素治疗２５例ＳＡＡ患者疗效尚好,现报告如下。一、对象与方法１－病例：２５例住院患者,男１５例,女１０例,年龄１０～６５岁。所有患者治疗前行血象、骨髓象、Ｈａｍ试验、血糖、肝、肾功能检查,并在治疗后定期复查,治疗前后血象、骨髓象见表１。２５例患者中重症Ⅰ型（ＳＡＡ…     

重型再生障碍性贫血85例治疗临床观察与分析

目的:观察采用异基因造血干细胞移植(Allo-HSCT)以及免疫抑制剂联合脐血输注治疗重型再生障碍性贫血(SAA)的疗效。方法:85例AA患者,有亲属全相合供者首选移植,无亲属全相合供者根据患者具体情况选择强烈免疫抑制剂联合脐血输注治疗或选择非血缘或不全相合移植方案治疗。其中42例SAA患者进行Allo-HSCT,43例SAA或极重型AA患者采用抗胸腺细胞球蛋白2.5~3.0 mg/(kg·d)×5d+环磷酰胺50mg/(kg·d)×2d联合非亲缘脐血输注支持治疗。结果:42例Allo-HSCT患者中,33例明显治愈,1例明显进步,1例无效,7例死亡,有效率为81.0%。43例强烈免疫抑制剂联合脐血输注的患者中,31例基本治愈,2例明显进步,3例无效,7例死亡,有效率为76.7%。总有效率为78.8%。结论:Allo-HSCT及免疫抑制剂联合脐血输注是治疗SAA的有效方法,均可取得满意的疗效。     

Cyclosporin A for the treatment of aplastic anemia refractory to antithymocyte globulin

Antithymocyte globulin (ATG) is an established form of therapy for severe aplastic anemia (SAA). However, in patients who do not respond to this treatment and who are not candidates for bone marrow transplantation few successful therapeutic alternatives exist. We report two such patients who have shown a therapeutic response to Cyclosporin A (CSA) (Sandimmune, Sandoz). Case 1, a 15 year old male, and Case 2, a 34 year old female, were diagnosed as having SAA in September 1984 and May 1984 respectively. Treatment with high dose Methylprednisolone (MPN) and ATG in Case 1 and MPN, ATG and Oxymetholone in Case 2 for ten days was ineffective in both cases. Case 1 developed anaphylaxis with both repeat ATG and ALG (antilymphoblast globulin), and Case 2 failed to respond to repeat ATG. Both required frequent packed cells and platelet transfusions. At five and six months respectively following completion of ATG therapy, CSA was started at 10 mg/kg/day in divided doses orally. Renal and liver functions and CSA blood levels were followed. Within six weeks both patients exhibited a hematologic response and were no longer transfusion dependent. On maintenance therapy of 4 mg/kg/day (Case 1) and four months after discontinuing CSA (Case 2) the hematologic values are as follows: hemoglobin 160 and 130 g/L, absolute granulocyte count 3100 and 1640 × 10⁹/L, and platelets 132 and 84 × 10⁹/L respectively. Side effects included hypertrichosis, gingival hyperplasia and mild reversible nephrotoxicity. CSA appears to represent an effective form of therapy for patients with SAA refractory to ATG.     

重型再生障碍性贫血细胞免疫功能异常与强化免疫抑制治疗的关系

重型再生障碍性贫血（SAA）患者骨髓造血功能衰竭的发生、发展与细胞免疫紊乱,特别是T细胞数量、功能的 异常密切相关,因此免疫功能异常在SAA的发病机制中起着重要的作用。目前抗胸腺细胞球蛋白（ATG）或抗淋巴细 胞球蛋白（ALG）联合环胞霉素A（CsA）的强化免疫抑制治疗（IST）对改善SAA 预后有显著疗效。IST 能够使 60％～80％的SAA患者得到血液学恢复即是异常免疫反应损伤造血干细胞的最直接证据。然而,由其他非免疫因 素介导或造血干细胞极度耗竭所致的骨髓衰竭,IST就可能无效。因此,在IST前进行疾病评估和疗效预测具有重要 意义,其中细胞免疫功能异常对初治SAA进行IST的疗效具有重要意义。     

Predicting response to immunosuppressive therapy in childhood aplastic anemia

In aplastic anemia, predictive markers of response to immunosuppressive therapy have not been well defined. We retrospectively evaluated whether clinical and laboratory findings before treatment could predict response in a pediatric cohort from the multicenter AA-97 study in Japan. Between 1997 and 2006, 312 newly diagnosed children were enrolled and treated with a combination of antithymocyte globulin and cyclosporine. In multivariate analyses, lower white blood cell count was the most significant predictive marker of better response; patients with white blood cell count less than 2.0×10(9)/L showed a higher response rate than those with white blood cell count of 2.0×10(9)/L or more (P=0.0003), followed by shorter interval between diagnosis and therapy (P=0.01), and male sex (P=0.03). In conclusion, pre-treatment clinical and laboratory findings influence response to therapy. The finding that response rate worsens with increasing interval between diagnosis and treatment highlights the importance of prompt immunosuppressive therapy for patients with aplastic anemia.     

Predictors of response to immunosuppressive therapy with antithymocyte globulin and cyclosporine and prognostic factors for survival in patients with severe aplastic anemia

Background: Immunosuppressive therapy (IST) with antithymocyte globulin (ATG) plus cyclosporine (CSA) is standard therapy in patients with severe aplastic anemia (SAA) who do not have an available HLA‐matched sibling donor. Methods and patients: The current study aimed to determine the predictive factors for response to IST in patients with SAA and to identify prognostic factors following IST. A total of 62 patients diagnosed with SAA who received IST with either rabbit ATG (n = 33) or horse ATG (n = 29) plus CSA between October 1994 and December 2007 were included. Results: With a median follow‐up duration of 60.5 months, complete response and overall response were estimated to be 31% and 53%, respectively. The 4 yr overall survival rate was 75 ± 6%. In terms of predicting the response to IST, neutrophil counts above 0.3 × 10⁹/L prior to IST were the only significant predictive factor (P = 0.02). Survival following IST was significantly different in favor of both the group showing high absolute reticulocyte counts (ARC) above 10.9 × 10⁹/L prior to IST (P = 0.004) and the group achieving any response following IST (P = 0.002). Conclusions: Pre‐IST neutrophil counts might predict the response to IST, while absolute ARCs prior to IST and response status after IST could be prognostic factors following IST.     

再生障碍性贫血患者联合免疫治疗前后IL-8表达水平的改变

目的:观察急性和慢性再障患者联合免疫疗法治疗前、后外周血和骨髓中白细胞介素8(IL-8)的含量变化和临床意义,并探讨其对监测再障疗效的可行性。方法:应用实时定量PCR和ELISA法检测外周血和骨髓IL-8的含量,流式细胞术分析外周血中CD4/CD8阳性细胞比值变化。结果:急性和慢性再障患者外周血和骨髓中IL-8含量均远高于正常对照者,且CD4/CD8出现倒置。抗淋巴细胞球蛋白(ALG)加环孢素A(CsA)加雄激素较CsA加雄激素治疗效果明显,总有效率分别为83.3%和62.5%。ALG加CsA加雄激素治疗重症再障较CsA加雄激素疗效显著。细胞因子水平改变和疗效明显相关。实时定量PCR和ELISA法正相关,但前者较易测出和量化。结论:ALG联合CsA治疗急、慢性再障疗效显著。细胞因子IL-8可以作为急、慢性再障的疗效监测指标。     

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。     

Hematopoietic growth factors in aplastic anemia patients treated with immunosuppressive therapy-systematic review and meta-analysis

Immunosuppressive therapy is the treatment for aplastic anemia patients ineligible for transplantation. The role of hematopoietic growth factors as adjunct to treatment in these patients is unclear. We conducted a systematic review and meta-analysis of randomized controlled trials comparing treatment with immunosuppressive therapy and hematopoietic growth factors to immunosuppressive therapy alone in patients with aplastic anemia. Two reviewers appraised the quality of trials and extracted data. For each trial, results were expressed as relative risks with 95% confidence intervals (CI) for dichotomous data. The addition of hematopoietic growth factors yielded no difference in overall mortality at 100 days, one year and five years [relative risks 1.33 (95% CI 0.56–3.18), relative risks 0.90 (95% CI 0.50–1.63) and relative risks 0.89 (95% CI 0.55–1.46), respectively]. There was no difference in overall hematologic response and in the occurrence of infections. HGF significantly decreased the risk for relapse, relative risks 0.45 (95% CI 0.30–0.68, 3 trials). Hematopoietic growth factors were not associated with higher occurrence of myelodysplastic syndrome and acute myeloid leukemia or paroxysmal nocturnal hemoglobinuria. The addition of hematopoietic growth factors does not affect mortality, response rate or infections occurrence. Therefore, it should not be recommended routinely as an adjunct to the immunosuppressive therapy for patients with aplastic anemia.     

Salvage therapy of refractory severe aplastic anemia by decreasing cyclosporine dose regimen

Optimal modalities for immunosuppressive therapy (IST) for severe aplastic anemia (SAA) have to be determined, and especially cyclosporine (CyA) dosing to promote regulatory T cells (Treg) which are lacking and which account for physiopathological mechanisms. We are reporting on three cases of pediatric patients suffering from SAA, initially without hematological response between 4 and 7 months after IST, and who have responded 2 months after the decrease in CyA target trough blood levels to 100 ng/mL, and one case which has early responded by applying low trough blood levels from the beginning. As it has been demonstrated that Treg increase in IST responders and that Treg are stimulated only by low CyA concentrations, these case series suggest that lower CyA doses than actually recommended could be more efficient to enhance the proportion of responders. This report highlights a new field of perspectives for the treatment for SAA.     

Acyclovir in the treatment of aplastic anemia

Eight patients with idiopathic severe aplastic anemia received acyclovir as the initial treatment to ascertain if this antiviral therapy could be effective. Three patients showed improvement, but only one had a sustained recovery. The responses could be coincidental, but it seems that some patients can benefit from acyclovir. More studies are needed on the role of viruses and antiviral therapy in relation to severe aplastic anemia.