目的观察和比较血缘与非血缘关系异基因外周血干细胞移植(allo—PBSCT)采用氟达拉滨(Flud)联合白消安(BU)组成的FB减低剂量预处理方案治疗慢性粒细胞白血病(CML)的疗效和移植相关并发症。方法采用FB(Flud30mg·m^2·d^-1×5d;Bu4mg·m^2·d^-1×3d)方案allo—PBSCT治疗CML共44例,接受血缘关系移植29例(血缘组),接受非血缘关系移植15例(非血缘组)。急性移植物抗宿主病(aGVHD)预防:血缘组为霉酚酸酯(MMF)+环孢素(CsA)+甲氨蝶呤(MTX),非血缘组在上述基础上另加兔抗人胸腺细胞球蛋白(ATG,5mg/kg×4d)。结果所有患者移植后均取得造血功能重建,血缘组与非血缘组中性粒细胞〉0.5×10^9/L的中位时间分别为13.7(9~18)d和13.6(12~17)d,血小板〉20×10^9/L的中位时间分别为15.3(9~20)d和14.7(10~26)d。但血缘组与非血缘组分别有2例与1例患者移植后5~8个月发生继发性植入排斥,其中血缘组1例再次行同一供体移植,重获造血功能重建。血缘组累计发生aGVHD共4例(13.8%),均为Ⅱ度;存活6个月以上28例患者中发生慢性GVHD(cGVHD)13例(46.4%),其中局限型和广泛型分别为10例和3例。非血缘组累计发生aGVHD共5例(33.3%),其中I~Ⅱ度4例,Ⅲ度1例;存活6个月以上14例患者中发生cGVHD8例(57.1%),其中局限型和广泛型分别为5例和3例。血缘组有2例患者移植后复发,给予冻存G—CSF动员的供者外周血干细胞输注(DSI)1~2次后再获得CR。本组中位随访时间34.7(2~73)个月,累计移植相关死亡10例(22。7%),主要死因是间质性肺炎、GVHD及继发排斥伴重症感染;34例患者存活,预期5年总生存率(OS)和无病生存率(DFS)分别为77.0%和73.9%;其中,血缘关系移植5年OS和DFS分别为79.O%和74.1%,非血缘关系移?
Objective To evaluate the overall efficacy and transplant-related mortality (TRM) of related and unrelated allogeneie peripheral blood hematopoietic stem cell transplantation (aIIo-PBSCT) in chronic myeloid leukemia (CML) patients conditioned with fludarabine-busulfan(FB) reduced intensity regimen. Methods Forty-four patients received FB(Flud30 mg ·m^2·d^-1×5 d, BU4 mg·m^2·d^-1×3 d ) conditioning followed by allo-PBSCT. Of them, 29 patients were transplanted with related donor and 15 unrelated donor (URD). All patients received mycophenolate mofetil (MMF), CsA and MTX for acute GVHD (aGVHD) prophylaxis. 5 ing/kg rabbit-antithymocyte globulin ( ATG-Fresenius ) was incorporated in 15 URD recipients. Results All patients were successfully engrafted. The median times to ANC above 0.5 × 10^9/L in related (RG) and unrelated groups (URG) were 13.7 (9 - 18 ) d and 13.6 ( 12 - 17) d, and PLT above 20 × 10^9/L were 15.3 (9 - 20) d and 14.7 ( 10 - 26) d, respectively. Two patients in RG. 1 in URG developed graft rejection 5 - 8 months after transplantation. One of the two patients in RG received second transplantation and engrafted. The cumulative incidence of aGVHD and cGVHD were 13.8% (4/29) and 46.4% (13/28) in RG, and were 33.3% (5/15) and 57.1% (8/14) in URG respectively. Two patients in RG relapsed after transplantation, and obtained CR again after donor stem cell infusion (DSI). Median time of follow-up was 34.7 (2 -73 ) months. Thirty-four patients were alive and 10 died. The main causes of death were IP, GVHD, graft rejection and infection. The 5-year overall survival (OS) probability was 77.0% , and the disease-free-survival (DFS) was 73.9% , of which, 79.0% and 74.1% were in RG, and 73.3% and 73.3% in URG, respectively. Conclusions Fludarabine-busulfan based reduced intensity conditioning for allo-PBSCT with either related or unrelated donors is a safe, less toxic and curative approach to CML.