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使用单克隆抗体清除骨髓的急性髓系白血病自体骨髓移植

Autologous bone marrow transplantation for acute myeloid leukemia using monoclonal antibody-purged bone marrow.

作者信息

Ball E D, Mills L E, Cornwell G G, Davis B H, Coughlin C T, Howell A L, Stukel T A, Dain B J, McMillan R, Spruce W

机构信息

Department of Medicine, Dartmouth-Hitchcock Medical Center, Hanover, NH.

出版信息

Blood. 1990 Mar 1;75(5):1199-206.

PMID:2306522
Abstract

We report our experience from a clinical trial of autologous bone marrow transplantation (ABMT) in the treatment of 30 patients with acute myeloid leukemia (AML) using monoclonal antibody (MoAb) and complement-treated bone marrow. All patients were in complete remission (CR) at the time of transplant: 6 patients were in first CR, 18 in second CR, and 6 in third CR. The median age of all patients was 42 years (range 11 to 57 years). For marrow ablation, 28 patients were treated with cyclophosphamide and total body irradiation. One patient was treated with busulfan and cyclophosphamide and one was treated with busulfan and VP-16. Each patient was then transfused with autologous bone marrow that had been harvested previously and treated with two MoAbs, PM-81 and AML-2-23, and rabbit complement. Median time to recovery of neutrophils (500/microL) was 30 days, and platelets (20,000/microL) was 45 days. Median time for initial erythrocyte engraftment, assessed by a flow cytometric reticulocyte assay, was 13 days. Median overall and relapse-free survival of first CR patients was at least 17.4 months post-ABMT and the 2- and 3-year actuarial overall and relapse-free survival was 67% (+/- 19%). Median survival for the 24 patients in second or third CR was 6.8 months post-ABMT and 9.3 months since CR; however, six patients survived disease-free from 16 to 61 months post-ABMT. For the second and third CR group it was observed that six patients (5 of the 6 survivors) showed "inversions," when their post-ABMT remission lasted longer than any previous one. Actuarial 2- and 3-year disease-free and overall survival of patients in second and third CR was 25% (+/- 9%) and 18% (+/- 9%), and 29% (+/- 9%) and 23% (+/- 9%), respectively. ABMT avoids the problems of graft-versus-host disease and of finding suitable donors for allogeneic marrow transplantation.

摘要

我们报告了一项自体骨髓移植(ABMT)临床试验的经验,该试验使用单克隆抗体(MoAb)和补体处理的骨髓治疗30例急性髓系白血病(AML)患者。所有患者在移植时均处于完全缓解(CR)状态:6例处于首次CR,18例处于第二次CR,6例处于第三次CR。所有患者的中位年龄为42岁(范围11至57岁)。对于骨髓消融,28例患者接受了环磷酰胺和全身照射治疗。1例患者接受了白消安和环磷酰胺治疗,1例患者接受了白消安和VP - 16治疗。然后,每位患者输注先前采集的自体骨髓,该骨髓已用两种单克隆抗体PM - 81和AML - 2 - 23以及兔补体进行处理。中性粒细胞恢复至(500/微升)的中位时间为30天,血小板恢复至(20,000/微升)的中位时间为45天。通过流式细胞术网织红细胞测定评估的初始红细胞植入中位时间为13天。首次CR患者的中位总生存期和无复发生存期在ABMT后至少为17.4个月,2年和3年的精算总生存期和无复发生存期为67%(±19%)。第二次或第三次CR的24例患者的中位生存期在ABMT后为6.8个月,自CR起为9.3个月;然而,6例患者在ABMT后16至61个月无病存活。对于第二次和第三次CR组,观察到6例患者(6名幸存者中的5例)出现“反转”,即他们的ABMT后缓解期持续时间长于以往任何一次缓解期。第二次和第三次CR患者的精算2年和3年无病生存期及总生存期分别为25%(±9%)和18%(±9%),以及29%(±9%)和23%(±9%)。ABMT避免了移植物抗宿主病以及为异基因骨髓移植寻找合适供体的问题。

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