异基因造血干细胞移植治疗伊马替尼耐药Ph染色体阳性白血病

Allogeneic stem cell transplantation for patients with Philadelphia positive leukemia resistant to imatinib

目的探讨造血干细胞移植（HSCT）作为甲磺酸伊马替尼（IM）耐药的费城染色体阳性（Ph＋）白血病挽救性治疗的疗效。方法回顾性分析2002年7月至2006年8月北京大学人民医院血液病研究所住院的14例IM耐药Ph（＋）白血病患者行异基因（allo）-HSCT的效果，其中复发／难治急性淋巴细胞白血病（ALL）3例，慢性髓性白血病加速期（CML—AP）1例，慢性髓性白血病急变期（BC）10例；7例行HLA配型完全相合同胞间移植，7例行HLA配型不相合亲缘移植；采用重组人粒细胞集落刺激因子（rhG—CSF）动员的骨髓（BM）加外周血干细胞（PBSC）混合移植8例，单用PBSC移植6例；10例患者给予预防或治疗性rhG—CSF动员后的供者淋巴细胞输注（DLI）。结果所有病例均达到完全供者型造血重建，移植后中性粒细胞和血小板植活的中位时间分别为16d和13d；发生Ⅱ度急性移植物抗宿主病（aGVHD）7例，Ⅲ度aGVHD2例，局限型慢性移植物抗宿主病（cGVHD）4例，广泛型cGVHD6例；血液学复发9例；无早期移植相关死亡。结论联合应用多种方法预防白血病复发，HSCT可作为IM耐药Ph（＋）白血病患者重要的挽救治疗选择。

Objective To investigate the effect of allogeneic hemopoietic stem cell transplantation （HSCT） in patients with acute lymphocytic leukemia （ALL） or chronic myelocytic leukemia （CML） resistant to imatinib mesylate （IM）. Methods Fourteen patients with ALL [ n = 4, all with Ph （ ＋ ） chromosome] or CML （n = 10, 1 in acceleration phase and 4 in blastic crisis） resistant to IM received allogeneic HSCT. The hematopoietic stem cells transplanted to 7 cases were from identical sibling donors, and hematopoietic stem cells transplanted to the other 7 were from mismatched related donors. Eight cases received recombinant human granulocyte-colony stimulating factor （rhG-CSF） mobilized bone marrow transplantation plus peripheral blood stem cell transplantation （PBSCT）, and 6 only received PBSCT. Ten cases were given rhG-CSF mobilized donor lymphocyte infusion （DLI） to prevent or treat relapsing. Results All patients achieved complete allogeneic engraftment and the median times of neutrophil recovery and platelet recovery were 16 and 13 days respectively. There was no treatment related death. Nine of the 14 patients developed acute graft versus host disease （GVHD） , 7 being in the grade lI and 2 being in grade Ⅲ ; and 6 of the 13 evaluable patients developed extensive chronic GVHD. The hematological relapse was 9. Conclusion Allo-HSCT can be an important salvage option for patients with Ph （ ＋ ） chromosome with leukemia resistant to IM.