含氟达拉滨的预处理行异基因造血干细胞移植治疗恶性血液病的远期疗效

目的:观察含氟达拉滨的预处理方案进行异基因造血干细胞移植治疗恶性血液病的长期疗效。方法:选取2003年2 月至2004年12月间厦门大学附属中山医院收治的15例恶性血液病患者，其中急性髓性白血病3 例，急性淋巴细胞白血病5 例，慢性粒细胞白血病6 例，骨髓增生异常综合症（RAEB）1 例。供受者HLA 配型同胞全相合6 例，同胞或亲缘不相合8 例，非亲缘全相合1 例。预处理方案采用氟达拉滨（Flu 30mg/m2·d，共5d）、马利兰（BU4mg/kg·d，共2～3d）、环磷酰胺（CTX 50mg/kg·d，共2d），其中8 例加用阿糖胞苷（Ara-c 1.0～2.0g/m2·d，共2d），9 例HLA 不全相合及非血缘移植者加用兔抗胸腺细胞球蛋白（ATG 3.0～5.0mg/kg·d，共3d）。 预防移植物抗宿主病（GVHD）均采用骁悉（MMF）+ 环孢素（CsA）+ 短程甲氨喋呤（MTX）方案。利用SPSS11.5 统计软件及Kaplan-Meier 方法进行生存分析。结果:15例患者移植后均获得快速完全的植入，无严重的预处理相关毒性。46.7% 发生急性GVHD ，85.7% 发生慢性GVHD ；带状疱疹7.1% 。5 年总生存率为53.5% ，其中移植时处于第一次完全缓解（CR1）和慢性期患者11例，5 年生存率为72.7% ，复发率9.1% ，移植时处于第二次完全缓解（CR2）、复发、加速期及急变期的患者4 例，2 年生存率为0，复发率75，两者有统计学差异（P=0.000 3 和P<0.05），主要死亡原因为疾病复发和GVHD 。结论:对于移植时处于CR1 和慢性期患者，采用含Flu并适当减低放化疗剂量的预处理方案是有效的移植预处理方案，毒副作用较少，未增加机会性感染，复发率较低；预处理中加入Flu对GVHD 发生率无明显影响。 

Long-term Efficacy of A Conditioning Regimen Containing Fludarabine in Allogeneic Hematopoietic Stem Cell Transplantation for Hematologic Malignancies

Objective:To investigate the long-term efficacy of a conditioning regimen containing fludarabi -ne in allogeneic hematopoietic stem cell transplantation (allo-HSCT) for hematologic malignancies. Methods: Patients with acute myelogenous leukemia (n=3), acute lymphoblastic leukemia (n=5), chronic myelogenous leukemia ( n=6), and myelodysplastic syndrome ( n=1) received allo-HSCT between February 2003 and De-cember 2004. There were 6 HLA-identical sibling donors, 8 family partially mismatched donors and 1 unrelat-ed donor. The conditioning regimen consisted of fludarabine (Flu30mg/m 2 ·d for5 days), busulfan (BU 4mg/ kg·d for3 days) and cyclophosphamide (CTX 50mg/kg·d for2 days). Ara-C (1.0~2.0g/m 2 ·d for2 days) was added in 8 patients and rabbit anti-T-lymphocyte globulin (3.0～5.0mg/kg.d for3 days) was added in 9 HLA-mismatched and unrelated patients. All patients received cyclosporine, short-term methotrexate and my-cophenolate mofetil for prophylaxis of graft-versus-host disease (GVHD). The 5-year overall survival rates were analyzed by Kaplan-Meier method.Results: All of the patients were successfully engrafted, with no se-vere regimen-related toxicity. The incidence of acute GVHD and chronic GVHD was 33.3% and 85.7% , re-spectively. Shingles occurred in7.1% of the patients. The 5-year overall survival (OS) was 53.3% for all of the patients. The 11patients who received transplantation during the first CR or chronic phase had higher overall survival rate than the 4 patients who received transplantation in the second CR, relapse, accelerated phase or blastic phase (72.7% versus0, P=0.0003). The main causes of death were relapse and GVHD. Conclusion:Al -lo-HSCT following a fludarabine-based reduced intensity conditioning regimen is an effective option for pa -tients transplanted in the first CR or chronic phase. This type of treatment plan has a low relapse rate and?does not increase extramedullary toxicity or the infection rate. For the patients transplanted in the first CR or chronic phase, addition of fludarabine to the conditioning regimen has no effect on GVHD in allo-HSCT.