非亲缘异基因造血干细胞移植治疗白血病的临床研究

A Clinical Study of Unrelated Allogeneic Hematopoietic Stem Cell Transplantation for Patients with Leukemia

目的探讨非血缘关系异基因造血干细胞移植（URD-SCT）的疗效和相关并发症。方法22例白血病患者接受URD-SCT治疗。预处理方案：所有患者均采用马利兰联合环磷酰胺（BUCY2）或改良BUCY2预处理方案。移植物抗宿主病（GVHD）预防：22例均采用酶酚酸酯（MMF）＋环孢素A（CsA）＋短程甲氨蝶呤（MTX）方案，其中，4例用猪抗淋巴细胞球蛋白（ALG），16例于移植0d和移植后4d使用赛尼哌（CD25单抗），2例同时用ALG和CD25单抗。供者细胞回输：输注有核细胞中位数为4．5×10^8／kg，CD34^＋细胞中位数为4．3×10^6／kg。结果1例早期死亡不能评估，1例未植活，20例经血型、染色体及DNA多态性检测证实植活。急性Ⅱ～Ⅳ度GVHD8例；慢性GVHD8例：局限性3例，广泛性5例。感染：移植后100d内感染者17例，病原学确诊为细菌感染3例，真菌感染2例，巨细胞病毒（CMV）感染6例。存活情况：100d内死亡5例，100d后死亡5例，其余患者无病存活。结论进一步降低移植相关并发症已成为URD-SCT需解决的首要问题。对无血缘供者的高危白血病患者，在严格控制移植适应证情况下，URD-SCT仍是治疗的重要手段之一。

Objective To study the therapeutic effectiveness and associated complications of unrelated allogeneic hematopoietic stem cell transplantation （URD-SCT）. Methods Twenty-two patients with leukemia received URD-SCT. All cases were subjected to BUCY2 or modified BUCY2 regimen. The graft-versus-host disease （GVHD） was prevented by mycophenolate mofetil （MMF）, ciclosporin A and short-term MTX regimen. Four cases received antilymphocyte globulin （ALG）, and 16 were administered with Zenapox （CD25MAb） on the day of transplantation and day 4 after transplantation. Two cases were administrated with ALG and CD25MAb. While transfusing the median of nucleated cells was 4, 5 × 10^8/kg and that of the CD34^＋ cells was 4.3× 10^6/kg. Results One case could not be evaluated due to death in the early stage after transplantation and one case suffered from primary graft failure. Twenty cases had engrafted identified by blood type, chromosome test and DNA polymorphism. Eight cases developed grade Ⅱ-Ⅳ acute GVHD. Eight patients experienced chronic GVHD：local in 3 cases, extensive in 5 cases. Infection within 100 days after URD-SCT was documented in 17 cases. Three cases presented bacterial infection, 2 suffered fungal infection and 6 had cytomegatovirus infection. Five cases died within 100 days and another 5 died 100 days after URD-SCT. Twelve cases have survived. Conclusion Reducing the high transplantation-related mortality is the first and foremost problem needed to overcome. To those high risk leukemic patients without matched-sibling donor, URD-SCT is still favorable for leukemia therapy.