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）治疗儿童生障碍性贫血的方法,疗铲和疗效相关因素。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１１例,明显进步８例,总有效率为６７．６５％;其中２９例ＳＡＡ总有效率为６５．５２％,１８例慢性重型再障（ＳＡＡ－Ⅱ）有效率为５５．５６％;     

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）。     

抗胸腺细胞球蛋白治疗再生障碍性贫血的疗效分析

应用抗胸腺细胞球蛋白（ＡＴＧ）治疗儿童再生障碍性贫血（简称再障）３０例。其中急性再障（ＳＡＡ－Ｉ）１０例，慢性重型再障（ＳＡＡ－ＩＩ）１１例，普通慢性再障（ＣＡＡ）９例。总有效率为５６．７％。３０例中有重型丙障（ＳＡＡ－Ｉ及ＳＡＡ－ＩＩ）共２１例，其中６例缓解，７例明显进步，总有效率为６１．９％。重型再障长期生存率为６８．４％。再障患儿治疗前有关临床资料与ＡＴＧ疗效关系分析提示，疗前外周血网织红细胞绝对计数＞１０×１０￣９／Ｌ及病程较短（＜６个月）者有效率高（Ｐ＜０．０５）。ＡＴＧ疗效与其他因素，如年龄、性别、免疫状态及疗前外周血粒细胞和血小板计数的高低无关。上述资料可以作为儿童再障应用ＡＴＧ治疗的病例选择及疗效预测参考指标。     

丽珠环明治疗儿童重型再生障碍性贫血的疗效观察

目的：观察国产环孢素Ａ（ＣｓＡ）丽珠环明在儿童重型再障（ＳＡＡ）中的临床疗效，并与传统的激素治疗组进行疗效对比。方法１１例ＳＡＡ儿采用康力龙＋肾上腺皮质激素治疗，３例ＳＡＡ同时加用丽珠环明进行临床随机对照治疗。结果ＣｓＡ组总有效率为７６．９％，对照组为３６．３％（Ｐ〈０．０５）。结论丽珠环明是治疗儿童ＳＡＡ的有效药物之一。     

环孢素A治疗再生障碍性贫血疗效观察

目的 了解环胞素Ａ（ＣＳＡ）联合用药与雄激素＋皮质激素治疗再障的疗效对比。方法 ＣＳＡ组应用ＣＳＡ＋康力龙＋泼尼松,对照组应用康力龙＋泼尼松,治疗前后行血象、骨髓像检查,治疗结果进行统计学处理。结果 ＣＳＡ组总有效率５４．５％,对照组２９．１％。重型再障中ＣＳＡ组有效率６６．７％,对照组３０％（Ｐ〈０．０５）;慢性再障中ＣＳＡ组有效率４０％,对照组２８．６％（Ｐ〉０．０５）。结论 ＣＳＡ不失为治疗     

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。     

儿童幽门螺杆菌相关性胃十二指肠疾病的药物治疗研究

目的 用克拉霉素（ＣＬＡ）与胶体次枸楷酸铋（ＣＢＳ）联合应用,加另一种抗生素,治疗儿童ＨＰ相关性胃炎,以评价不同治疗方案的疗效和观察要除ＨＰ感染与胃炎好转的关系。方法 ２７６例４～１４岁患儿经胃镜检查确诊为幽门螺杆菌（ＨＰ）相关性胃十二指肠疾病,随机分为Ａ、Ｂ、Ｃ、Ｄ两组,接受以ＣＢＳ为主的三联疗法。Ａ、Ｃ、Ｄ组用克拉霉素（ＣＬＡ）１５ｍｇ／ｋｇ．ｄ）联合ＣＢＳ９ｍｇ（ｋｇ．ｄ）,再加另一种抗生素     

去甲氧柔红霉素联合方案治疗难治性急性淋巴细胞白血病的远期疗效

目的探讨应用去甲氧柔红霉素（ＩＤ）为主的联合化疗方案治疗难治性儿童急性淋巴细胞白血病（ＡＬＬ）的远期疗效及其临床应用价值。方法初治诱导缓解方案用ＶＩＬＰ（长春新碱、去甲氧柔红霉素、左旋门冬酰胺酶、泼尼松）。完全缓解（ＣＲ）后作巩固治疗及庇护所治疗，然后再用ＶＩＬＰ作早期强化治疗。复发者诱导治疗用ＩＡ（去甲氧柔红霉素、阿糖胞苷）方案。ＣＲ后巩固和早期强化治疗用初治者同样方案。结果１０例初治患儿９例获ＣＲ，７例复治患儿５例获ＣＲ，总ＣＲ率为８２％（１４／１７）。ＣＲ的１４例中持续ＣＲ（ＣＣＲ）＞３年者４例，＞２年者４例，＞１年者１例。结论用去甲氧柔红霉素为主的联合方案是治疗难治性儿童ＡＬＬ有效的方法，对初治患儿作为一线药物其远期疗效会更好。     

多中心协作方案序贯治疗儿童高危型急性淋巴细胞白血病和晚期淋巴瘤

目的探讨应用多中心协作方案（ＭＣＰ）方案治疗儿童高危型急性淋巴细胞白血病（ＨＲＡＬＬ）和晚期非霍奇金淋巴瘤（ＮＨＬ）的远期疗效。方法患儿２７例。其中１５例ＨＲＡＬＬ和５例Ⅳ期ＮＨＬ采用ＭＣＰ８４１方案;７例Ⅲ期ＮＨＬ采用ＭＣＰ８４２方案。结果初治完全缓解（ＣＲ）率为１００％。ＨＲＡＬＬ和Ⅳ期ＮＨＬ的持续完全缓解（ＣＣＲ）率为８５％,７例ＮＨＬ均获得ＣＣＲ,ＣＣＲ时间中位数分别为４０个月和３７个月;未并发中枢神经系统白血病（ＣＮＳＬ）和化疗相关死亡。按ＫａｐｌａｎＭｅｉｅｒ法预测６年ＣＣＲ率可达８８％。测定血和脑脊液阿糖胞苷（ＡｒａＣ）浓度,应用大剂量ＡｒａＣ时血浓度可提高３５倍,脑脊液浓度可达４０％。结论ＭＣＰ化疗方案可以作为儿童ＨＲＡＬＬ和晚期ＮＨＬ的长期治疗方案。     

强化免疫抑制治疗儿童再生障碍性贫血疗效分析

探讨强化免疫抑制治疗儿童再生障碍性贫血(再障)的疗效。方法总结我院1991～1999年 儿童再障31例,根据治疗方法不同分3组对比观察基础治疗组(康力龙、654-2等),单用环孢菌素A(CSA)治 疗组,强化免疫抑制治疗组。结果基础治疗组、单用CSA组、强化免疫抑制治疗组有效率分别为27.27％,57.14％,76.92％;重型再障(SAA)有效率分别为11.11％,50.00％,75.00％;SAA-Ⅰ有效率分别为14.29％, 60.00％,88.89％。单用CSA组及强化免疫抑制治疗组疗效明显优于基础治疗组,强化免疫抑制组对SAA及 SAA-Ⅰ疗效更佳,有效率分别达75.00％和88.89％。结论以CSA为主的免疫抑制治疗比单用康力龙、654-2 等治疗更有效;对于SAA,CSA联合ALG/ATG、HDIVIG、HDMP等强化免疫治疗能提高疗效,对SAA-Ⅰ更明显。     

抗淋巴细胞球蛋白联合环胞霉素A治疗儿童重型再生障碍性贫血早期疗效观察

目的探讨提高儿童重型再生障碍性贫血(SAA)早期疗效的办法。方法采用随机对照方法,比较抗淋巴细胞球蛋白(ALG)和环胞霉素(CSA)联合治疗组与单用CSA组治疗儿童SAA的早期疗效(6个月)。结果联合治疗组和CSA组的总有效率分别为(84%)、(60%),P<0·05,联合治疗可降低早期死亡率,缩短脱离红细胞和血小板的输注时间。结论ALG联合CSA治疗儿童SAA是安全的且疗效佳,应作为一线方案。     

免疫抑制治疗获得性重型再生障碍性贫血患儿疗效分析

目的 分析免疫抑制治疗儿童获得性重型再生障碍性贫血(severe aplastic anemia,SAA)的近远期疗效.方法 回顾性分析2000年1月至2006年6月在我院应用联合免疫抑制治疗的获得性重型再生障碍性贫血患儿.112例患儿随机分3组:Ⅰ组(26例):单用环孢素A(CSA)组;Ⅱ组(30例):CSA+丙种球蛋白[400 mg/(kg·d)×5 d];Ⅲ组(56例):兔抗胸腺细胞球蛋白(R-ATG)[3～5 mg(kg·d)×5 d]+CSA.所有患儿治疗均同时加用司坦唑醇或丙酸睾丸酬.CSA血药浓度调整到谷浓度100 ug/L以上,峰浓度300 ug/L以上.结果Ⅰ组免疫抑制治疗的总反应率为26.92%;Ⅱ组免疫抑制治疗的总反应率为33.33%;Ⅲ组免疫抑制治疗的总反应率为62.5%,明显高于Ⅰ组(P=0.001);比较Ⅰ组与Ⅱ组的总反应率差异无统计学意义.Ⅰ、Ⅱ和Ⅲ组5年总生存率分别为(20.50±15.41)%、(39.77±9.77)%和(66.27±6.84)%.结论对无HLA匹配同胞供者的重型获得性再生障碍性贫血患儿ATG联合CSA是最理想的治疗方法 .     

儿童再生障碍性贫血临床特点及临床分型探讨

目的探讨儿童再生障碍性贫血(再障)临床特点及临床分型。方法2003-01—2005-12在中山大学附属第二医院儿科确诊儿童再障50例,年龄2～15岁,其中37例接受免疫抑制治疗(IST),观察再障发病诱因、临床表现、血象、骨髓象变化特点、临床分型及治疗转归。结果86%的儿童再障为特发性,70%患儿病程≤6个月,按疾病严重程度分型,临床诊断重型再障(SAA)38例,轻型再障(MAA)12例,骨髓有核细胞增生程度除与病情严重程度相关外,还与取材部位、病程及是否接受IST等因素有关。特发性再障患儿强化IST(IIST)及单用环孢菌素A(CsA)治疗6个月有效率分别为78.3%(18/23)和40.0%(4/10,χ2=4.59,P<0.05),多数患儿于IIST后2～3个月起效,仅1例病程2年余的SAA于IIST后7个月达部分缓解。结论儿童再障多数为特发性,起病急,病情重,临床表现及血象改变严重程度与骨髓增生减低程度相关,特发性再障患儿IIST疗效显著优于单用CsA治疗者,宜按国际标准根据病情严重程度分为重型和轻型。     

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     

Granulocyte-macrophage colony stimulating factor and immunosuppression in the treatment of pediatric acquired severe aplastic anemia

BACKGROUND: Immunosuppressive therapy (IS) is effective in the treatment of patients with acquired severe aplastic anemia (SAA). An enhanced myeloid response and decreased infection risk may be possible with the addition of a hematopoietic cytokine. Published data on the combination of cytokines and IS in patients with SAA are limited. The addition of G-CSF to IS shortens the time to neutrophil count recovery, but may not improve overall survival. Because GM-CSF acts differently than G-CSF, its use in combination with IS may be different. PROCEDURE: A retrospective chart review was performed on patients diagnosed with SAA and treated with IS and GM-CSF at St. Jude Children's Research Hospital. Hematologic recovery, prognostic factors, and infection data were collected. RESULTS: Eighteen patients were included in this study. The median age at diagnosis was 7.2 years (range 1.8-17.0). Ten patients (56%) had a complete response, four (22%) a partial response, and four (22%) no response. Median time to erythrocyte and platelet transfusion independence were 90 (18,243) and 64 days (18-243), and to discontinuation of treatment 287 days (90-730). Median time to partial (ANC > 500) and full (ANC > 1,500) neutrophil recovery were 41 and 51 days, respectively. Seventeen documented discrete infections occurred in six patients over 36 patient years. CONCLUSIONS: GM-CSF, in addition to IS, may shorten time to neutrophil count recovery, may be beneficial in decreasing infection rates, and may improve platelet response in patients with SAA. However, consistent with studies utilizing G-CSF, GM-CSF probably does not affect overall response rate. To fully answer whether or not cytokine therapy is of added value to IS in pediatric patients, a multi-institutional randomized trial is needed.     

儿童再生障碍性贫血免疫抑制剂治疗疗效及相关因素分析

目的：探讨免疫抑制疗法（IST）对儿童再生障碍性贫血（AA）的疗效及其影响疗效的相关因素。方法：对2003年2月至2009年11月住院接受IST治疗的、可进行疗效评估的110例AA患儿的临床资料进行回顾性分析。110例患儿中,重型AA（SAA）83例,非重型 AA（非SAA）27例。前者采用抗胸腺细胞球蛋白（ATG）联合环孢素（CSA）及泼尼松、雄激素四联治疗,后者采用CSA联合泼尼松、雄激素三联治疗。结果：SAA与非SAA组的总有效率分别为69.9%和70.4%。单因素分析显示病程、骨髓CD34+细胞比例、CD4+CD25+调节性T细胞比例与疾病严重程度相关,但与预后无关。治疗有效组患儿年龄、病程、骨髓CD3+、CD8+细胞比例显著低于治疗无效组（P<0.05）。多因素分析显示年龄＞10岁、骨髓CD8+细胞比例＞25%的患儿治疗失败的风险分别是对应组的3.36倍和3.59倍。结论：IST治疗儿童AA疗效确切。年龄、病程、CD3+、CD8+ T细胞水平与IST的疗效相关。     

Bone marrow transplantation in children with severe aplastic anemia using a conditioning regimen containing 3 Gy of total body irradiation, cyclophosphamide with or without antithymocyte globulin

We have employed the 3 Gy total body irradiation (TBI) containing conditioning regimen to bone marrow transplantation (BMT) for severe aplastic anemia (SAA) in pediatric patients irrespective of donor type since March 1986. The outcome of BMT for 17 SAA patients is favorable. Eight patients received BMT from human leukocyte antigen matched-related donors (MRD) and nine received BMT from alternative donors. The conditioning regimen consisted of 3-Gy TBI and cyclophosphamide of 200 mg/kg in the BMT from MRD. In the case of BMT from alternative donor, antithymocyte globulin 10 mg/kg was added to the regimen. Fifteen of 17 patients (88%) engrafted on median of day 18 (range, 11-26) and all 13 evaluable patients showed complete donor chimerism by median 30 (range, 13-47) days after BMT. Fourteen patients have survived with a median follow-up of 67 (range, 2-228) months and the probability of survival was 81.9% (95% CI, 63.3-100%). No late complications including second malignancies caused by TBI have been observed and all three female patients have regular menstruation. In conclusion, TBI of 3 Gy appears to be an appropriate dose regarding to ensure engraftment and avoid the risk of late adverse event for SAA patients.     

Antithymocyte globulin and cyclosporin in children with acquired aplastic anemia

Objective  To assess the responses to ATG and cyclosporin combination in patients of aplastic anemia. Methods  Twenty three (17M: 6F) patients of aplastic anemia (11 very severe aplastic anemia (VSAA) and 12 severe aplastic anemia (SAA), were administered antithymocyte globulin and cyclosporin. Results  The median age of patents was 8 years (range 6–12 years). Three patients died within 2 months of therapy. Twenty children (11 SAA and 9 VSAA) were finally analysed. Six months after the start of treatment, 8/20 (40%) patients responded-2 complete (CR) and 6 partial responses (PR). At the end of 1 year; 2 patients maintained CR and seven patients continued PR (overall responders 45%). The response was better in SAA (54.5%) with 2 CR and 4 PR; than in VSAA (33%) with 3 PR. Eleven (55%) children were alive without response. One patient developed AML 13 months later. Conclusion  We conclude that antithymocyte globulin and cyclosporin combination is an effective treatment for aplastic anemia patients who are ineligible for bone marrow transplantation.     

Rabbit Antithymocyte Globulin Treatment in Childhood Acquired Severe Aplastic Anemia

Acquired severe aplastic anemia (SAA) is a life threatening bone marrow failure characterized by pancytopenia and hypocellular bone marrow. Matched sibling donor is not available for majority of the patients and many children receive immunosuppressive therapy (IST). Although horse antithymocyte globuline (ATG) is the preferred option, our patients received rabbit ATG; since horse ATG is not available in Turkey. We reviewed the medical records of children with SAA who were treated with rabbit ATG, cyclosporine, and granulocyte colony stimulating factor (GCSF) between 2006 and 2012. Fifteen children with SAA aged between 1.5 and 17 years received rabbit ATG as first line treatment. Only two of them showed partial response and the others did not give any response at 3rd, 6th, and 12th months after the first course of IST. The second course of ATG was given to 8 of the patients; Rabbit ATG at the same dosage was used for 3 of them, and others were given horse ATG. None of the patients responded to the second course of ATG. Invasive fungal infection (IFI) which was seen in 80% of the patients was the most significant problem. Overall survival rate was 60%. The median time between the diagnosis and initiation of IST was 57 (range; 29–144) days. This delay might be significantly contributed to unresponsiveness. In our series, the use of rabbit ATG was not effective for these patients as first line treatment modality. Response rate was very low and the incidence of fungal infections was very high in the SAA patients who received rabbit ATG.