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目的:评价采用一种新预处理方案行异基因造血干细胞移植(allo-HSCT)治疗慢性粒细胞白血病(CML)患者的疗效。方法:2005年1月-2008年12月对43例CML患者进行allo-HSCT,采用白消安加环磷酰胺联合氟达拉滨、阿糖胞苷(Bu/Cy/Flu/Ara-C)为预处理方案,具体剂量为Bu3.2mg·kg-1·d-1静点(iv)或4mg·kg-1·d-1口服(po)2～4d、Cy50mg·kg-1·d-1×2、Flu30mg·m-2·d-1×3、Ara-C2g·m-2·d-1×3。移植方式为HLA相合或半相合亲缘供者造血干细胞移植,其中外周血干细胞移植(PBSCT)16例,骨髓移植(BMT)26例,骨髓加外周血干细胞移植1例。结果:所有患者均获造血重建,发生Ⅱ～Ⅳ度急性移植物抗宿主病(aGVHD)12例(27.9%),慢性GVHD(cGVHD)19例(45.2%),移植相关死亡(TRM)9例(20.9%),细胞遗传学或血液学复发6例(14.0%),其中4例复发后采用格列卫与DLI联合的挽救治疗获得稳定的分子生物学缓解;总体无病生存率(DFS)为(72.0±7.0)%,其中CP1和非CP1期移植患者DFS分别为(80.0±6.7)%和(42.9±18.7)%。移植后90d内出现bcr/abl阳性与持续阴性者分别为31例(72.1%)和12例(27.9%),2组累积复发率分别为(21.4±8.0)%和(9.1±8.7)%(P=0.427)。单因素及多因素分析提示广泛型GVHD为影响DFS的危险因素。结论:采用新预处理方案进行亲缘供者allo-HSCT治疗CML疗效良好。移植后90d内bcr/abl阳性不足以提示复发。格列卫联合供者淋巴细胞输注是治疗CML早期复发的一种有效方法。
OBJECTIVE: To evaluate the efficacy of allo-HSCT in the treatment of patients with chronic myeloid leukemia (CML) using a novel preconditioning regimen. Methods: Forty-three patients with CML were enrolled in this study. Allo-HSCT was performed in patients with CML from January 2005 to December 2008. The patients were treated with busulfan plus cyclophosphamide combined with fludarabine and cytarabine (Bu / Cy / Flu / Ara-C) As the pretreatment protocol, the specific dose was Bu3.2 mg kg-1 d-1 intravenous (iv) or 4 mg kg-1 d-1 orally for 2 to 4 days, Cy50 mg kg-1 d- 1 × 2, Flu30 mg · m-2 · d-1 × 3, Ara-C2g · m-2 · d-1 × 3. Hematopoietic stem cell transplantation was HLA matched or semi-matched donor, including 16 cases of peripheral blood stem cell transplantation (PBSCT), 26 cases of bone marrow transplantation (BMT) and 1 case of bone marrow plus peripheral blood stem cell transplantation. RESULTS: All patients underwent hematopoietic reconstitution. Twelve patients (27.9%) had grade Ⅱ ~ Ⅳ acute graft-versus-host disease (aGVHD), 19 (45.2%) had chronic GVHD and 9 had transplant-related death (20.9%), cytogenetics or hematological relapse in 6 cases (14.0%), of which 4 cases relapsed after treatment with Gleevec and DLI in combination with the salvage therapy to obtain stable molecular biological response; overall disease-free survival (DFS) (72.0 ± 7.0)%, respectively. The DFS in the patients with CP1 and non-CP1 grafts were (80.0 ± 6.7)% and (42.9 ± 18.7)%, respectively. There were 31 cases (72.1%) and 12 cases (27.9%) with positive or negative persistent bcr / abl within 90 days after transplantation. The cumulative recurrence rates were (21.4 ± 8.0)% and (9.1 ± 8.7)% P = 0.427). Univariate and multivariate analysis indicated that extensive GVHD is a risk factor for DFS. Conclusion: Allo-HSCT treatment of CML with new preconditioning regimen is effective. Bcr / abl positive within 90 days after transplantation is not enough to prompt recurrence. Glivec co-donor lymphocyte infusion is an effective treatment for early relapse of CML.