亲缘HLA半相合造血干细胞移植治疗进展期慢性髓性白血病

Haploidentical blood and marrow transplantation for advanced chronic myeloid leukemia

目的 探讨亲缘HLA半相合造血干细胞移植（haplo-BMT）治疗进展期慢性髓性白血病（CML）的疗效.方法 2002年1 1月至2007年10月,35例进展期CML患者接受了haplo-BMT.移植前评估11例患者经过伊马替尼和（或）化疗达到第二次慢性期（CP2）,13例处于加速期（AP）,11例为急变期（BP）.截止到2011年10月31日,存活患者的中位随访时间为67个月（49～100个月）.结果 供、受者HLA 1～3个抗原不相合的例数分别是1、12和22例.输注的单个核细胞（MNC）数及CD34＋数分别为（7.19±1.37）×108/kg及（2.54±1.50）×106/kg.除1例受者早期死亡外,其余34例（97％）患者获得造血重建.超急性移植物抗宿主病（ GVHD）发生率为28.6％（10/35）,Ⅱ度及以上急性GVHD的累积发生率为48％,27例存活时间超过100d的受者中有16例（60％）发生慢性GVHD.100d内死亡率为20％（7/35）.入院时处于AP及BP患者的5年总存活率分别为46.2％和45.5％（P＞0.05）.移植前处于CP2、AP及BP者移植后5年预计总存活率分别为81.8％、30.8％和27.3％,CP2组显著高于其他两组（P＜0.01）.结论 Haplo-BMT是无HLA相合供者的进展期CML的有效治疗方案.移植前达到CP2可显著提高存活率.

Objective To investigate the efficacy of haploidentical blood and marrow transplantation （haplo-BMT） in the treatment of advanced chronic myeloid leukemia （CML）.Methods From November 2002 to October 2007,35 patients with advanced CML received haplo-BMT.Eleven patients achieved the second chronic phase （CP2） after treatment with imatinib or chemotherapy or both before pre-conditioning,but there were 13 cases in accelerated phase （AP） and 11 patients in blast phase （BP） at the time of transplantation.By the last follow-up date October 31,2011,the median follow-up time among living patients was 67 months （range,49 to 100 months）.Results The cases of HLA-antigen mismatched between donors and recipients as 1,2,and 3 antigens were 1,12,and 22 respectively.The number of mean mononuclear cells and CD34＋ cells was （7.19＋ 1.37） × 108/kg and （2.54± 1.50） × 106/kg,respectively.All but one patient achieved durable hematopoietic reconstitution. Hyperacute graft-versus-host disease （GVHD） occurred in 28.6% （10/35） patients.The cumulative incidence of grade Ⅱ to Ⅳ acute GVHD was 48%.Among 27 patients who survived longer than 100 days after transplant,16 （60 %） had chronic GVHD.Fiveyear overall survival （OS） rate was 46.2% and 45.5% in CML-AP and BP （P =0.97）,respectively.Five-year probability of OS rate was 81.8%,30.8% and 27.3% in patients with CML-CP2,CML-AP and BP at transplant,respectively.The OS of CML-CP2 was significantly higher than CML-AP and BP at transplant （P〈0.01 ）.Conclusion Haplo-BMT is a feasible therapeutic mean for patients with advanced CML who have no matched donors available.It is better to perform haplo-BMT at CML-CP2 other than CML-AP or BP.