非亲缘异基因骨髓移植治疗急性和慢性白血病

目的评价非亲缘异基因骨髓移植（URD-BMT）治疗急性和慢性白血病的临床疗效以及并发症的防治方法。方法由台湾慈济骨髓捐赠中心提供HLA相合非亲缘供髓，对11例急性白血病和慢性白血病患者进行骨髓移植术，其中急性淋巴细胞性白血病2例（CR1）、急性髓细胞性白血病2例（ANLL-CR1）、慢性髓细胞性白血病7例。10例患者预处理方案为移植前7至4d马利兰(BU)4mg·kg-1·d-1，移植前3至2d环磷酰胺（CTX）60mg·kg-1·d-1。1例慢粒急淋变患者预处理方案全身放疗(TBI)7.5GY，移植前4至3d环磷酰胺60mg·kg-1·d-1。供髓输注有核细胞（2.6～4.8）×108/kg，CD34+细胞（3.82～12.8）×106/kg，粒单-集落形成单位(CFU-GM)（1.71～3.68）×105/kg。预防急性移植物抗宿主病（aGVHD）方案霉酚酸酯（MMF）+环孢菌素A（CsA）+短程氨甲喋呤（MTX）。预防肝静脉阻塞病（VOD）方案低剂量肝素持续静滴加前列腺素E1脂质微球（Lipo-PGE1）。以更昔洛韦预防巨细胞病毒感染（CMV）方案。非亲缘供髓与受者间HLA-A、B、DR基因型完全相合8例，1个亚型不相合2例，2个亚型不相合1例。结果全部患者移植后均获得造血重建，中性粒细胞>0.5×109/kg中位时间18d，血小板>20×109/L中位时间27d。10例患者经DNA短串联重复序列多态性分析证明为供者骨髓植活。发生急性GVHDⅣ度1例，aGVHDⅡ度2例，重度VOD和Ⅲ度房室传导阻滞1例，出血性膀胱炎3例，死于间质性肺炎1例，1例患者于移植后7个月复发，予以供者淋巴细胞输注，目前尚处于治疗中。无病生存10例。结论非亲缘异基因骨髓移植术是急性和慢性白血病有效治疗方法。本组患者对aGVHD、VOD和CMV采用的预防方案是有效和安全的。

Unrelated donor allogenetic marrow transplantation in treatment of acute and chronic leukemia

OBJECTIVE: To evaluate the clinical efficacy against acute and chronic leukemia of unrelated donor allogenetic marrow transplantation (URD-BMT) and to develop methods of preventing and treating complications of URD-BMT. METHODS: Eleven patients, 2 with acute lymphatic leukemia, 2 with acute myelocytic leukemia, and 7 with chronic myelocytic leukemia, were treated by URD-BMT. The median age of the 11 patients, 6 male and 5 females, were 26 years. The conditioning regimen for 10 patients was: BU 4 mg.kg(-1).d(-1) x 4 + CTX 60 mg.kg(-1).d(-1)1 x or TBI 7.5 Gy + CTX 60 mg.kg(-1).d(-1) x 2. Bone marrow with karyocytes in the dose of (2.6 approximately 4.8) x 10(8)/kg, including CD34+ cells in the dose of (3.82 approximately 12.8) x 10(6)/kg, and with the CFU-CM in the dose of (1.71 approximately 3.68) x 10(5)/kg, were transfused. Mycophenolate mofitil, cyclosporine, and methotrexate were given to prevent acute graft-versus-host disease (aGVHD). Continuous intravenous drip of heparin in low dose with Lipo protaglandin E1 was given to prevent hepatic veno-occlusive disease (VOD). Ganciclovir was used to prevent CMV infection. HLA phenotype was matched in 8 cases, mismatched in one locus in 2 cases, and mismatched in 2 loci in one case. RESULTS: Hematopoietic reconstruction was successful in all of the patients with the neutrophil count of 0.5 x 10(9)/L on the 10th day after transplantation and the platelet count of more than 20 x 10(9)/L on the 27(th) day. Analysis of DNA short series repeated sequence polymorphism showed the survival of bone marrow after transplantation in ten cases. One case of IV grade aGVHD, one case of II grade aGVHD, one case of serious VOD and III grade artrioventricular block, three cases of hemorrhagic cystitis, and one case of interstitial pneumonia occurred, the last case being died. Recurrence of leukemia occurred in one case seven months after the transplantation. That case was given the transfusion of donor's lymphocytes and has been so far under treated. Ten cases are alive in disease-free situation till now. CONCLUSION: URD-BMT is an effective method for the treatment of acute and chronic leukemia. The prophylaxis regimen against aGVHD, VOD, and CMV that we use is effective and safe.