同胞全相合异基因造血干细胞移植治疗95例骨髓增生异常综合征患者的临床分析

The clinical analysis of allogeneic hematopoietic stem cell transplantation from human leukocyte antigen-identical siblings in 95 patients with myelodysplastic syndrome

目的 探讨同胞全相合异基因造血干细胞移植（allo-HSCT）治疗骨髓增生异常综合征（MDS）的疗效与时机.方法 回顾分析2003年1月-2012年12月采用同胞全相合allo-HSCT治疗MDS及MDS转急性髓性白血病（AML） 95例.采用改良马利兰＋环磷酰胺或氟达拉滨的预处理方案,行骨髓和/或外周血干细胞移植.结果 95例患者中93例白细胞植活,Ⅱ～Ⅳ度急性移植物抗宿主病（aGVHD）累计发生率为12.9％±3.5％;慢性移植物抗宿主病（cGVHD）3年累计发生率为80.3％±4.9％.3年累计复发率（RR）为25.9％±4.7％,非复发死亡率（NRM）为16.1％±4.0％.3年预期总生存（0S）率及无病生存（DFS）率分别为69.9％±5.0％和58.0％±5.4％.多因素分析显示,发生Ⅱ～Ⅳ度aGVHD和不发生cGVHD是OS的独立危险因素;国际预后积分系统（IPSS）分组是DFS的独立预后因素.将难治性贫血伴原始细胞增多转化型（RAEB-t）及MDS转AML患者（31例）分为移植前未化疗、化疗未缓解、化疗缓解3组,3年OS率分别为33.9％、32.7％、100.0％,化疗缓解组OS率明显高于另外两组（P＜0.05）,DFS率、RR率差异无统计学意义.结论 同胞全相合allo-HSCT是治疗MDS的有效手段,IPSS可预测移植后疗效,对于移植前疾病进展的患者,争取缓解后行allo-HSCT可能提高疗效,但尚需进一步临床对照研究.

Objective To evaluate the efficacy and optimize the timing of allogeneic hematopoietic stem cell transplantation （allo-HSCT） from human leukocyte antigen （HLA）-identical siblings for myelodysplastic syndrome （MDS）. Methods From January 2003 to December 2012, 95 patients with MDS or secondary acute myeloid leukemia （AML） were treated with HLA-identical allo-HSCT in our hospital. The median age was 43 （21-59） years. Conditioning regimens including modified busulfan （Bu）/ cyclophosphamide （Cy） or Bu/fludarabine （Flu） were used. All patients received transfusion of donor stem cells mobilized by granulocyte colony-stimulating factor （G-CSF） from bone marrow and/or peripheral blood. Eleven patients had refractory anemia （RA） or RA with ringed sideroblasts, 53 of RA with excess blasts （RAEB） , 15 of RAEB in transformation （ RAEB-t）, and 16 progressing to secondary AML. Results A total of 93 patients achieved sustained myeloid engraftment. The cumulative incidence of grade Ⅱ-Ⅳ acute graft versus host disease （aGVHD） was 12. 9% ±3.5%. The 3-year cumulative incidence of chronic graft versus host disease （cGVHD） was 80. 3% ± 4. 9%. After a median follow-up of 28. 7 months, 29patients died. The 3-year estimated overall survival （OS） and disease-free survival （DFS） rates were 69. 9% ± 5.0% and 58.0% ± 5.4% respectively. The cumulative relapse rate （RR） was 25.9% ±4. 7% , while non-relapse mortality （NRM） was 16.1% ± 4.0%. Multivariate analyses showed that non Ⅱ-Ⅳ aGVHD and cGVHD were favorable factors associated with OS. Low DFS rate was correlated with high scores of international prognostic scoring system （IPSS）. Patients with RAEB-t and AML （n = 31 ） were divided into 3 groups ： no chemotherapy before HSCT （ Group 1 ）, chemotherapy but not achieving remission （ Group 2） and chemotherapy and achieving remission （Group 3 ）. The 3-year OS rate was 100. 0% in Group 3, which was significantly higher than those of Groups 1 and 2 with 33.9%, 32. 7% respectively （P 〈 0. 05）. The difference of DFS and RR in the three groups did not reach statistic difference. Conclusions Allo- HSCT from HLA-identical siblings is effective for patients with MDS. IPSS is of prognostic value for post- transplantation outcome. For patients with progressive disease before transplantation, maximal control of blasts in bone marrow may improve the prognosis of advanced MDS.