供者用粒细胞集落刺激因子单倍体骨髓移植的临床研究

目的探讨供者用粒细胞集落刺激因子(G-CSF)和受者联合应用多种免疫抑制剂治疗的单倍体骨髓移植在降低重症移植物抗宿主病(GVHD)和改善无病生存的疗效.方法单倍体骨髓移植治疗白血病13例(单倍体移植组),移植后结果和连续完成的13例白血病HLA匹配异基因移植 (相合移植组) 相比较,单倍体移植方法是供者应用G-CSF 250 μg/d,连用7 d后采髓, 受者GVHD预防除环孢素A(CSA)和甲氨蝶呤(MTX)外,在移植前4～1 d用抗胸腺细胞球蛋白(ATG) 5 mg*kg-1*d-1, 移植后7 d始加服霉酚酸酯(MMF).结果单倍体移植组植入物CD+34细胞中位数6.1×106/kg,是相合移植组输入CD+34细胞中位数2.5×106/kg的2倍多(P＜0.01),单倍体移植组和相合移植组植入物CD+3细胞中位数分别是50.5×106/kg和47.0×106/kg(P＞0.05).移植后无1例发生植入失败,两组造血重建速度无差异(P＞0.05),所有患者经骨髓植活直接证据检测证实为完全供者造血.单倍体移植组发生急性Ⅱ～Ⅳ GVHD 5例(38.5%),可评价的8例中7例发生慢性GVHD(87.5%),为局限性慢性GVHD,这与相合移植组差异无显著性 (P＞0.05).单倍体移植组中位随访453 d(180～690),移植相关死亡5例,无复发死亡病例,剩余8例无病存活(61.5%).相合移植组中位随访510 d(220～810),移植相关死亡2例,复发死亡2例,9例无病存活(69.2%),通过比较两组差异无显著性(P＞0.05).结论本研究单倍体骨髓移植治疗白血病是一种安全和有效方法,在降低重症急性GVHD 及改善无病生存方面和HLA相合同胞供者移植相当.

A clinical study of haploidentical transplantation using granulocyte colony-stimulating factor stimulating donor bone marrow

OBJECTIVE: To explore the effects of reducing the incidence of severe acute graft-versus-host disease (GVHD) and improving the disease free survival(DFS) in haploidentical donor transplantation by granlocyte colony-stimulating factor (G-CSF) administration to donor before harvesting and a number of immunosuppresants added to host. METHODS: Thirteen patients with leukemia received allo-bone marrow transplantation (BMT) from two or three HLA loci mismatched related donor (haploidentical group). The clinical outcomes of the bone marrow transplantion were compared with thase of 13 consecutive HLA identical sibling transplantion (identical group). In haploidentical donor BMT, the donors of patients were given G-CSF (Lenograstim Chugai) 250 micrograms/day for seven doses prior to marrow harvest. CSA, MTX, ATG and mycophenolate mofetil (MMF) were combined for GVHD prophylaxis. ATG 5 mg/kg/day was infused for 4 days before transplantation and MMF was adminisered from 7th day after. RESULTS: All the patients were engrafted. The median number of CD34+ cells in graft was 6.1 x 10(6)/kg in haploidentical group and 2.5 x 10(6)/kg in identical group (P < 0.01). The median number of CD3+ cells was 50.5 x 10(6)/kg and 47.0 x 10(6)/kg respectively (P > 0.05). All patients had 100% donors hematopoietic cells after transplantation by cytogenetic evidence analysis. Five of the thirteen patients (38.5%) in haploidentical group and three of the thirteen patients(23.1%) in identical group experienced II-IV acute GVHD (P > 0.05). The probability of chronic GVHD was 87.5% in haploidentical group and 67.5% in identical group (P > 0.05), However none in both groups developed extensive cGVHD. The median follow-up duration was 453 days (range 180-690 days) for haploidentical group and 510 days (range 220-810 days) for identical group. In haploidentical group, five patients died from transplant related mortality (3 GVHD, 2 infection), none relapsed and eight patients(61.5%) survive in disease free situation. In identical group, two patients died from transplant related mortality (1 GVHD, 1 infection), two patients died from relapse and nine patients (69.2%) survive in disease free situation. DFS in haploidentical group and in identical group was similar(P > 0.05). CONCLUSION: The transplants from haploidentical donor used in this study is 3 effective and feasible in preventing acute severe GVHD and improving DFS.