抗淋巴细胞免疫球蛋白(猪)联合环孢素治疗重型再生障碍性贫血

目的 评价国产猪抗淋巴细胞免疫球蛋白(ALG)+环孢素(CsA)治疗重型再生障碍性贫血(SAA)的疗效.方法 回顾性分析1999年至2009年48例(男31例,女17例)联合应用猪ALG和CsA治疗的SAA患者资料,观察治疗后的近期及长期疗效、并发症及转归,并根据患者的年龄、疾病严重程度、发病距使用ALG的时间及治疗前有无感染进行分层分析.结果 48例患者中位年龄为28(13～64)岁.从诊断到治疗的中位时间为45 d.发病时患者中性粒细胞中位数为0.178×109/L.48例患者中26例(54.2%)基本治愈,14例(29.2%)缓解,总有效率为83.3%,恢复时间为90(23～380)d.治疗后短期死亡5例(10.4%),主要死亡原因为感染(真菌为主).1例患者2年后复发,无进展为克隆性疾病的病例.1.5年的生存率为87.5%.极重型再生障碍性贫血(vSAA)患者总有效率、早期死亡率及总生存率均较SAA患者差(64.7%、29.4%、51.8%vs93.5%、0、100%,P值均＜0.01).不同年龄、性别、诊断至治疗的时间及治疗前是否合并感染组的治疗有效率差异无统计学意义(P值均＞0.05).主要不良反应为发热、皮疹(52.1%)、血清病(16.7%)、肝功能损伤(60.4%)、出血(2.1%),无治疗相关死亡率.结论 采用国产猪ALG联合CsA对初治SAA患者有较理想的疗效,且较传统的马或兔ATG,猪ALG的治疗费用更经济.vSAA者预后不佳.

Abstract：

Objective To evaluate the efficacy of porcine anti-human lymphocyte globulin (P-ALG)plus cyclosporine A (CsA) therapy for severe aplastic anemia (SAA). Methods Forty-eight SAA patients (31 males, 17 females) including 17 very severe aplastic anemias (vSAA)were treated with ALG plus CsA between 1999 to 2009 in our hospital and the outcomes were analyzed retrospectively for early mortality, response rate and quality, survival rate, toxicity and complications. Results The median age was 28 (13 -64) years. The interval from diagnosis to treatment was 45 days. The median neutrophil count at diagnosis was 0. 178 × 109/L. Overall response was 83.3% (54.2% complete, 29.2% partial) with a median time of 90 (23 -380) days. 10.4% died of infection within 30 days mainly of fungi infection. Only 1 patient relapsed 2 years after treatment. No clonal disease was found. The 1.5-year survival rate was 87.5%. vSAAs had less response, higher early mortality and less survival (64.7%, 29.4% and 51.8%, respectively) compared to that of SAA (93.5% ,0, 100%, respectively, P ＜ 0. 05). Grouped patients with different age, gender, intervals between diagnosis and treatment and pre-existing infections had similar response. The main side effects were fever and skin rash (52.1%), serum sickness(16. 7%), impaired liver function(60.4%)and hemorrhage(2.1%). No treatment-related mortality was found. Conclusion P-ALG plus CsA is an ideal and well tolerated treatment for SAA but not for vSAA.     

抗淋巴细胞免疫球蛋白(猪)联合环孢素治疗重型再生障碍性贫血

Objective To evaluate the efficacy of porcine anti-human lymphocyte globulin (P-ALG)plus cyclosporine A (CsA) therapy for severe aplastic anemia (SAA). Methods Forty-eight SAA patients (31 males, 17 females) including 17 very severe aplastic anemias (vSAA)were treated with ALG plus CsA between 1999 to 2009 in our hospital and the outcomes were analyzed retrospectively for early mortality, response rate and quality, survival rate, toxicity and complications. Results The median age was 28 (13 -64) years. The interval from diagnosis to treatment was 45 days. The median neutrophil count at diagnosis was 0. 178 × 109/L. Overall response was 83.3% (54.2% complete, 29.2% partial) with a median time of 90 (23 -380) days. 10.4% died of infection within 30 days mainly of fungi infection. Only 1 patient relapsed 2 years after treatment. No clonal disease was found. The 1.5-year survival rate was 87.5%. vSAAs had less response, higher early mortality and less survival (64.7%, 29.4% and 51.8%, respectively) compared to that of SAA (93.5% ,0, 100%, respectively, P ＜ 0. 05). Grouped patients with different age, gender, intervals between diagnosis and treatment and pre-existing infections had similar response. The main side effects were fever and skin rash (52.1%), serum sickness(16. 7%), impaired liver function(60.4%)and hemorrhage(2.1%). No treatment-related mortality was found. Conclusion P-ALG plus CsA is an ideal and well tolerated treatment for SAA but not for vSAA.     

抗淋巴细胞免疫球蛋白(猪)联合环孢素治疗重型再生障碍性贫血

Objective To evaluate the efficacy of porcine anti-human lymphocyte globulin (P-ALG)plus cyclosporine A (CsA) therapy for severe aplastic anemia (SAA). Methods Forty-eight SAA patients (31 males, 17 females) including 17 very severe aplastic anemias (vSAA)were treated with ALG plus CsA between 1999 to 2009 in our hospital and the outcomes were analyzed retrospectively for early mortality, response rate and quality, survival rate, toxicity and complications. Results The median age was 28 (13 -64) years. The interval from diagnosis to treatment was 45 days. The median neutrophil count at diagnosis was 0. 178 × 109/L. Overall response was 83.3% (54.2% complete, 29.2% partial) with a median time of 90 (23 -380) days. 10.4% died of infection within 30 days mainly of fungi infection. Only 1 patient relapsed 2 years after treatment. No clonal disease was found. The 1.5-year survival rate was 87.5%. vSAAs had less response, higher early mortality and less survival (64.7%, 29.4% and 51.8%, respectively) compared to that of SAA (93.5% ,0, 100%, respectively, P ＜ 0. 05). Grouped patients with different age, gender, intervals between diagnosis and treatment and pre-existing infections had similar response. The main side effects were fever and skin rash (52.1%), serum sickness(16. 7%), impaired liver function(60.4%)and hemorrhage(2.1%). No treatment-related mortality was found. Conclusion P-ALG plus CsA is an ideal and well tolerated treatment for SAA but not for vSAA.     

国产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

目前国内外均认为免疫介导的造血抑制是再生障碍性贫血(AA)的主要发病机制,重型AA是其中一个临床类型,该型起病急,预后凶险,感染、出血是其主要的病死原因.2004年04月至今本院对13例患者使用国产抗淋巴细胞球蛋白联合环孢素A、康力龙治疗SAA取得较好的疗效,并且副作用小、价格便宜.     

抗淋巴细胞球蛋白治疗重型再生障碍性贫血的近期血液学反应及疗效观察

目的:观察抗淋巴细胞球蛋白(antilymphocyte globulin,ALG)治疗重型再生障碍性贫血(severe aplasticanemia,SAA)的临床疗效、血液学指标(淋巴细胞比例、中性粒细胞计数)的近期变化、副作用(超敏反应、血清病)、并发症(感染、出血)、输血支持及住院时间等情况。方法:对2005年3月至2007年4月于我院采用ALG治疗的7例SAA患者的临床资料进行分析并追踪随访。结果:所有患者外周血淋巴细胞比例均于ALG治疗后迅速下降,中位下降64%(14%~68%),并维持一段时间。中性粒细胞计数在治疗期间轻度下降,住院期间所有患者均发生感染,其中细菌感染1例,细菌合并真菌感染4例,细菌合并病毒感染1例,真菌合并病毒感染1例,予相应抗感染治疗均康复出院。7例患者治疗后均出现超敏反应,表现为发热、皮疹及瘙痒,出现时间最早为第1天,最迟为第12天,中位时间为第2天,持续1~3天。1例患者于治疗第13天发生血清病,表现为皮疹及水肿,经积极抗过敏治疗,所有患者未中断免疫抑制治疗。住院期间中位输注红细胞悬液9u(2u~11u),血小板5治疗量(1~8治疗量),除2例未脱离输血外,其余5例平均23天脱离输血(14~26天)。无一例患者出现中枢神经系统或胃肠道等严重出血。治疗后评价疗效:4例有效,1例部分有效,1例无效,1例随访时间1月暂未评价疗效,随访时间1~27月,中位随访时间13月。中位住院日46天(28~77 天)。结论:予以及时抗感染、抗过敏及积极支持治疗,ALG治疗SAA安全、有效,是没有HLA相合同胞供者的SAA患者首选的治疗措施。     

抗人体淋巴细胞免疫球蛋白治疗重症再生障碍性贫血的护理

总结了12例重症再生障碍性贫血强化免疫抑制治疗的护理措施。包括在给予输血、防治感染等对症支持治疗的基础上,采用抗人体淋巴细胞免疫球蛋白治疗,加强各项护理措施,减少并发症的发生。认为加强患者的心理护理、采用正确的用药方法、加强病情观察及用药后的观察和护理,可以明显提高患者的疗效和生活质量,延长无病生存时间。     

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

重型再生障碍性贫血 (ｓｅｖｅｒｅａｐｌａｓｔｉｃａｎｉｍｉｎ ,ＳＡＡ) ,特别是急性再生障碍性贫血 (ＡＡＡ)病情进展迅速 ,预后凶险 ,感染、出血所致的早期病死率高。 2 0 0 0年 4月～ 2 0 0 2年 3月 ,我们对 3例ＳＡＡ患者采用了抗淋巴细胞球蛋白 (ＡＬＧ)联合环孢菌素Ａ(ＣｓＡ)治疗收到较好的疗效 ,现报告如下。1　资料与方法1.1　一般资料　 3例患者中男 2例 ,女 1例 ;年龄 10～ 41岁。均符合我国现行ＳＡＡ诊断标准[1] 。患者一般临床特征见表1。表 1　 3例重型再生障碍性贫血患者的一般临床特征病例 年龄(岁 ) 性别 病程(月 )血…     

大剂量免疫球蛋白治疗重型再生障碍性贫血

大剂量免疫球蛋白治疗重型再生障碍性贫血宋艳秋李舜华易永林李薇高素君姜振宇姚程我们试用大剂量免疫球蛋白（ＨＤＩＶＩｇ）治疗重型再生障碍性贫血（ＳＡＡ），收到了良好的疗效，现报告如下。材料和方法１病例选择１．１球蛋白治疗组：１０例患者年龄１９～５２岁，男...     

环孢素与左旋咪唑交替治疗非重型再生障碍性贫血疗效观察

目的探讨环孢素(CsA)与左旋咪唑交替治疗初治非重型再生障碍性贫血(NSAA)疗效和安全性。方法 2007年1月至2013年1月收治的52例初治NSAA,随机分为两组,每组26例。观察组为CsA 5 mg·kg-1·d-1隔日口服(与左旋咪唑交替)12个月,左旋咪唑2.5 mg·kg-1·d-1隔日口服(与环孢素交替)12个月,对照组为CsA 5 mg·kg-1·d-1口服12个月。观察比较两组血常规、网织红细胞恢复、治疗效果及不良反应(肾功能损害、高血压、牙龈增生等)发生率。结果观察组血红蛋白、网织红细胞、中性粒细胞恢复和对照组比较均无统计学差异(P>0.05);血小板恢复稍差于对照组,有统计学差异(P<0.05)。观察组缓解(CR)率为19.05%,明显进步(PR)率为47.62%,有效(TR)率为66.67%,和对照组相比无统计学差异(P>0.05)。观察组无肾功能损害及高血压发生,胃肠道反应发生少,牙龈增生发生率低(7.69%),均低于对照组(P<0.05)。结论 CsA与左旋咪唑交替治疗NSAA有效,不良反应少,节省费用,可作为NSAA患者切实可行的治疗方案。     

环孢素联合十一酸睾酮对慢性再生障碍性贫血患者T辅助细胞水平的影响研究

目的研究环孢素联合十一酸睾酮对慢性再生障碍性贫血患者T辅助细胞水平的影响。方法选择在该院接受治疗的慢性再生障碍性贫血患者86例作为研究对象,根据患者治疗方案不同分为接受十一酸睾酮联合环孢素治疗的研究组和接受十一酸睾酮治疗的对照组,比较2组患者治疗前后的血常规指标,以及Th1、Th2、Th17、Treg细胞含量。结果治疗前,2组患者间血红蛋白含量、白细胞计数、血小板计数,以及外周血Th1、Th2、Th17、Treg细胞含量的比较,差异无统计学意义(P0.05)。治疗2个疗程后,研究组患者的血红蛋白含量、白细胞计数、血小板计数均明显高于对照组。治疗2个疗程、4个疗程后,研究组患者外周血中Th1细胞、Th17的含量明显低于对照组,Th2、Treg细胞的含量明显高于对照组。结论十一酸睾酮联合环孢素治疗能够更为有效地刺激造血、调节免疫功能及T淋巴细胞亚群含量,是治疗慢性再生障碍性贫血的有效方法。     

氯化锂联合环孢素A对再生障碍性贫血小鼠的治疗作用

本研究旨在探讨Wnt信号激活剂氯化锂联合环孢素A对再生障碍性贫血(AA)小鼠的治疗作用。54只BALB/c AA模型小鼠,随机分为3组:AA对照组、环孢素A治疗组、环孢素A联合氯化锂治疗组,每组18只。造模当天起分别腹腔注射环孢素A 50 mg/(kg.d)和氯化锂20 mg/(kg.d),连续5 d,于造模后14、21、28 d观察每组小鼠的疗效,检测指标包括外周血白细胞计数,血红蛋白含量,骨髓单个核细胞计数,骨髓活检增生程度。结果表明,与正常组比较,第14和21天AA组小鼠外周血细胞计数、骨髓单个核细胞数明显降低,骨髓切片HE染色骨髓腔中充满脂肪细胞,第28天造血无明显改善;与AA组比较,环孢素A组及联合用药组外周血细胞计数、骨髓单个核细胞数明显升高,骨髓脂肪细胞明显减少,差异有统计学意义(P<0.05);联合用药组与环孢素A组比较外周血细胞计数、骨髓单个核细胞数有明显升高(P<0.05),骨髓脂肪细胞量减少,骨髓造血接近于正常。结论:Wnt信号激活剂氯化锂联合环孢素A治疗AA的效果较单独应用环孢素A治疗的效果更好,能促进骨髓造血功能的恢复,其机理可能与Wnt信号激活后抑制骨髓基质干细胞向脂肪细胞分化有关。     

重型再生障碍性贫血的研究进展

重型再生障碍性贫血（SAA）是由多种病因导致的骨髓造血功能衰竭,以造血干细胞损伤、造血微环境异常及免疫功能紊乱导致严重的贫血、感染、出血为临床表现的重度骨髓衰竭性疾病。SAA 发病机制复杂,至今尚未完全明了。随着医疗水平的提高,人们对于 SAA 的认识已从宏观微观有了质的飞跃。目前对 SAA 病因的研究热点主要集中在 T 细胞亚群的异常、负性调控因子水平的改变、细胞凋亡等,现就这些方面的研究进行综述。     

抗淋巴细胞球蛋白联合环孢霉素A治疗重型再生障碍性贫血的临床研究

目的探讨进一步提高重型再生障碍性贫血（ＳＡＡ）疗效的方法。方法采用前瞻性同期对照研究方法,比较抗淋巴细胞球蛋白（ＡＬＧ）单用（ＮＩＳＴ方案）或联合环孢霉素Ａ（ＣｓＡ）（ＩＳＴ方案）治疗ＳＡＡ的疗效。结果ＩＳＴ方案组不仅疗效（８３７％）显著高于ＮＩＳＴ方案组（５７６％）,且可降低早期死亡率、缩短脱离红细胞输注时间,治疗有效者骨髓ＢＦＵＥ和ＣＦＵＧＭ数量恢复更为良好。结论ＡＬＧ联合ＣｓＡ治疗ＳＡＡ疗效明显优于单用ＡＬＧ,且治疗有效者骨髓造血功能恢复更为完全。     

Efficacy of anti-thymocyte globulin for platelet transfusion refractoriness in serious aplastic anemia patients

Platelet transfusion refractoriness (PTR) is a life threatening, intractable clinical issue suffered by some serious aplastic anemia (SAA) patients. Unlike immune thrombocytopenia, effective treatments for PTR remain largely unknown. In our clinical work, we noted that PTR in some SAA patients could be rapidly relieved with the application of anti-thymocyte globulin (ATG), therefore, we retrospectively analyzed its management and outcomes for PTR in SAA patients. A cohort including 29 SAA with PTR patients who received ATG administration was enrolled in this study. All patients suffered from PTR before ATG administration. Among the 29 PTR patients treated with ATG, 21 (72.4.0 %) patients had response, importantly, 13 (44.8 %) patients had an immediately response following the first dose of ATG administration. Bleeding events of grade 3 or above occurred in 23 patients (79.3 %). With the recovery of effective platelet transfusion, the bleeding events in responders could be quickly relieved. The non-responders suffered from aggravated bleeding, including intracranial bleeding in two non-responders, which appeared on eighth and 29th days after ATG administration. Our study indicated that ATG was an effective and safe intervention in the management of PTR in SAA patients.     

一线应用兔源抗胸腺细胞球蛋白联合环孢素治疗成人重型再生障碍性贫血疗效分析

目的 研究成人重型再生障碍性贫血(SAA)一线应用兔源抗胸腺细胞球蛋白(r-ATG)联合环孢素(CsA)免疫抑制治疗(IST)的疗效及不良反应.方法 回顾性分析我院2003年至2008年贫血诊疗中心收治的79例成人初始SAA或极重型再生障碍性贫血(VSAA)患者临床资料,评价IST疗效及分析相关因素.结果 6例患者早期死亡,73例患者可进行疗效评价,60例(82.2%)获得治疗反应,获得治疗反应的患者脱离输注血制品的中位时间为60 d.32例SAA患者均获治疗反应,治疗反应率(100%)高于41例VSAA组患者的68.3%(P=0.001).获得G-CSF治疗反应的患者较无反应者IST疗效明显增高(100%对67.5%,P=0.001).共61例(77.2%)患者出现血清病反应.获得治疗反应的患者3例复发,2例发生克隆性血液学异常.应用该方法治疗,患者预计3年总生存率为88.9%.结论 一线应用r-ATG联合CsA治疗成人SAA疗效高,不良反应轻微.

Abstract：

Objective To analyze the efficacy and side-effects of combination of rabbit antithymocyte globulin (ATG) and cyclosporine A(CsA) as the first-line immunosuppressive therapy (IST) for adult severe aplastic anemia ( SAA ) patients. Methods Adult SAA or very severe aplastic anemia ( VSAA ) patients treated with rabbit ATG + CsA as first line therapy in our hospital from 2003 to 2008 were retrospectively analysed and the therapeutic response relevant factors were analysed. Results Seventy-nine patients were enrolled. Of all these patients, 6 died within 3 months after IST. The overall response rate was 82.2% and the median time to transfusion independent was 60 days. The therapeutic response rate in 32 SAA patients ( 100% ) was significantly higher than that in 41 VSAA cases (68.3%) ( P = 0.001 ). Patients with neutrophil response to G-CSF treatment had a higher IST response rate than those without response to G-CSF ( 100% vs 67.5%, P=0.001 ). Sixty-one patients (77.2%) occurred serum sickness reaction. Three patients relapsed and two developed clonal hematological abnormdities after IST. The 3-year overall survival for all the patients was 88.9%. Conclusions Rabbit ATG in combination with CsA as first-line IST for adult SAA can lead to excellent treatment outcomes with minor adverse effects.     

环孢菌素A并11—酸睾丸素治疗慢性再生障碍性贫血

目的 为进一步观察环孢菌素A（CsA)联合十一酸睾丸素治疗慢性再生障碍性贫血（CAA）的疗效。方法 比较单用十一酸睾丸素与CsA联合十一酸睾丸素治疗CAA的疗效。结果 CsA联合十一酸睾丸素治疗组有效率为83.6%，明显高于单用十一酸睾丸素对照组的56.3%。结论 CsA联合十一酸睾丸素治疗CAA疗效明显高于单用十一酸睾丸素。