HLA半相合未去除T细胞骨髓移植治疗白血病的初步观察

目的探索半相合未去除T细胞骨髓移植治疗白血病的可行性.方法15例白血病患者接受HLA2～3个位点不匹配亲缘骨髓移植.用阿糖胞苷、环磷酰胺和γ射线全身照射进行预处理,供者应用G-CSF250μg/d,连用7d后采髓,移植物抗宿主病(GVHD)预防除用环孢菌素A(CsA)和甲氨蝶呤(MTX)外,在移植前第4天～第1天用抗胸腺细胞球蛋白ATG5mg@kg-1@d-1,移植后第7天开始加用霉酚酸酯1.0g/d.结果患者移植后均获得造血重建,中性粒细胞＞0.5×109/L和血小板＞20×109/L的中位时间分别是19d(13～23d)和21d(16～32d).5例(33.3%)发生急性Ⅱ～Ⅳ度GVHD,其中急性Ⅱ度肠道GVH2例,急性Ⅲ度肠道GVHD2例,急性肠道和肝脏Ⅳ度GVHD1例.可评价的9例患者中8例发生慢性GVHHD,无一例发生广泛性慢性GVHD.中位随访时间395d(110～690d),死亡6例,其中死于急性GVHD3例,死于感染2例,复发死亡1例.无病存活9例,其中6例存活在1年以上.结论供者应用G-CSF后采髓,多种免疫抑制剂联合应用的HLA半相合未去除T细胞骨髓移植,在治疗自血病过程中,有效地降低了急性重症GVHD发生,提高了无病生存,对拓宽供髓来源有重要实用价值.

Preliminary study of HLA haplotype matched and T-cell undepleted allogeneic bone marrow transplantation for treatment of leukemia

OBJECTIVE: To explore the feasibility of allogeneic bone marrow transplantation (Allo-BMT) with graft from HLA haplotype matched related donor without T-cell depleted for the treatment of leukemia. METHODS: Fifteen patients with leukemia received allo-BMT with grafts from HLA 2 or 3 antigen mismatched related donors. All patients were treated with standardized conditioning regimen consisting of high dose Ara-C, cyclophosphamide (CY) and total body irradiation (TBI). Donors were given G-CSF at 3 to 4 micrograms.kg-1.d-1 for seven days prior to marrow harvest. GVHD prophylaxis programme consisted of CsA, MTX, ATG and mycophenolate mofetial. RESULTS: All patients established successful engraftment. The median days of granulocyte > 0.5 x 10(9)/L and platelet > 20 x 10(9)/L were 19(range 13-23) and 21 (range 16-32) days, respectively. Acute grade II-IV GVHD occurred in 5 of 15 patients (33.3%). Two of them were grade II gut aGVHD, 2 grade III gut aGVHD, and 1 grade IV gut and liver aGVHD. Chronic GVHDs were seen in 8 of 9 evaluable patients (88.9%) and none developed extensive cGVHD. The median follow-up duration was 395 (110-690) days. Six of fifteen patients died. Five of them died from transplantation related mortality and 1 from relapse. Nine patients were alive in a disease-free situation. Six of them survived more than one year. CONCLUSION: The major histoincompatibility barriers in the haplotype matched related donor/recipient allo-BMT might be crossed by donor stimulated with G-CSF and combined GVHD prophylaxis program.