Nagler A, Aker M, Or R, Naparstek E, Varadi G, Brautbar C, Slavin S
Department of Bone Marrow Transplantation, Hadassah University Hospital, The Hebrew University-Hadassah School of Medicine, Jerusalem, Israel.
Exp Hematol. 2001 Mar;29(3):362-70. doi: 10.1016/s0301-472x(00)00655-x.
Matched unrelated bone marrow transplantation (BMT) for patients with hematological malignancies is associated with a high incidence of transplant-related complications due to high doses of chemoradiotherapy administered pre-BMT to ensure engraftment. The aim of this study was to investigate the feasibility of low-intensity conditioning for BMT from matched unrelated donors.
Sixteen patients with hematologic malignancies underwent non-T-cell-depleted BMT following a low-intensity conditioning regimen consisting of fludarabine monophosphate 30 mg/m(2)/day for 6 days, busulfan 4 mg/kg/day for 2 days, anti-T lymphocyte globulin 10 mg/kg/day for 4 days. Seven of the patients suffered from chronic myelogenous leukemia, four from acute lymphoblastic leukemia, four from acute myelogenous leukemia, and one from Ki-1 non-Hodgkin's lymphoma. Three of the patients had secondary leukemia and two were post-autologous BMT (ABMT). All patients were transplanted from fully matched unrelated donors.
Fifteen of the 16 patients had 100% donor chimerism; no graft rejection was observed. None of the patients developed >Grade II veno-occlusive disease, sepsis, multiorgan failure, or renal or pulmonary toxicity. Four patients died posttransplant; one of thrombocytopenia and severe hemorrhagic cystitis, one of central nervous system toxicity, one of Grade IV graft-vs-host disease, and one following relapse (9 months post-BMT). Survival and disease-free survival at 36 months are 75% (95% confidence interval 46-90%) and 60% (95% confidence interval 30-80%), respectively.
These results indicate that low-intensity conditioning is sufficient to ensure stable engraftment of bone marrow grafts in a matched unrelated setting.
由于在非亲缘骨髓移植（BMT）前需给予高剂量放化疗以确保植入，血液系统恶性肿瘤患者进行非亲缘骨髓移植时与移植相关并发症的高发生率相关。本研究的目的是探讨对非亲缘供者进行低强度预处理的BMT的可行性。
16例血液系统恶性肿瘤患者接受了非T细胞去除的BMT，采用低强度预处理方案，包括单磷酸氟达拉滨30mg/m²/天，共6天；白消安4mg/kg/天，共2天；抗T淋巴细胞球蛋白10mg/kg/天，共4天。其中7例患者患有慢性粒细胞白血病，4例患有急性淋巴细胞白血病，4例患有急性髓细胞白血病，1例患有Ki-1非霍奇金淋巴瘤。3例患者患有继发性白血病，2例为自体骨髓移植（ABMT）后患者。所有患者均接受来自完全匹配的非亲缘供者的移植。
16例患者中有15例出现100%供者嵌合；未观察到移植物排斥。所有患者均未发生>Ⅱ级静脉闭塞性疾病、败血症、多器官功能衰竭或肾或肺毒性。4例患者移植后死亡；1例死于血小板减少和严重出血性膀胱炎，1例死于中枢神经系统毒性，1例死于Ⅳ级移植物抗宿主病，1例死于复发（BMT后9个月）。36个月时的生存率和无病生存率分别为75%（95%置信区间46-90%）和60%（95%置信区间30-80%）。
这些结果表明，低强度预处理足以确保在非亲缘匹配情况下骨髓移植物的稳定植入。
