Full haplotype-mismatched hematopoietic stem-cell transplantation: A phase II study in patients with acute leukemia at high risk of relapse

Full haplotype-mismatched hematopoietic stem-cell transplantation: A phase II study in patients with acute leukemia at high risk of relapse
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DOI:
10.1200/jco.2005.09.117
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发表时间:
2005-05-20
影响因子:
45.3
通讯作者:
Martelli, MF
Martelli, MF
中科院分区:
医学1区
文献类型:
--
作者:
Aversa, F;Terenzi, A;Martelli, MF

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目的建立非相合亲属造血干细胞移植治疗急性白血病的可行性。由于我们最初的移植物处理方法不适合大规模临床研究,我们使用自动化设备进行CD 34+细胞纯化。(AML; 19例完全缓解[CR] 1,14例CR 2,9例CR > 2,25例复发)和37例急性淋巴细胞白血病(ALL; 14例CR 1,8例CR 2,2例CR > 2,13例复发)用全身照射、塞替派和抗胸腺细胞球蛋白处理。外周血祖细胞动员氟达拉滨,与重组人粒细胞集落刺激因子和耗尽的T细胞使用CD 34+细胞免疫选择。结果101例可评估的患者中有94例获得了一期植活。7例排斥初次移植的患者中有6例在第二次移植后移植。总体而言,101例患者中有100例植入。100例患者中有8例发生急性GvHD,70例可评估患者中有5例发生慢性GvHD。38例患者死于非白血病原因。66例接受移植的缓解期患者中有9例复发,38例接受移植的复发期患者中有17例复发。40例无事件存活患者的中位随访时间为22个月(范围:1至65个月)。无事件生存率(+/-标准差)分别为48%+/-8%和46%+/-10%,为42 AM L和24 ALL患者接受移植在remission.Conclusion我们的移植程序提供了可靠的,可重复的CD 34+细胞纯化,高植入率,和预防GvHD。对于没有匹配供体的急性白血病患者和/或迫切需要移植的患者来说,错配相关移植是一种可行的替代干细胞来源。(c)2005年美国临床肿瘤学会
Purpose Establishment of hematopoietic stem-cell (HSC) transplantation from mismatched relatives is feasible for patients with acute leukemia. As our original method of graft processing was unsuitable for large-scale clinical studies, we use automated devices for CD34+ cell purification.Patients and Methods Sixty-seven patients with acute myeloid leukemia (AML; 19 complete remission [CR] 1, 14 CR 2, nine CR > 2, 25 in relapse) and 37 with acute lymphoid leukemia (ALL; 14 CR 1, eight CR 2, two CR > 2, 13 in relapse) were conditioned with total-body irradiation, thiotepa, and antithymocyte globulin. Peripheral-blood progenitor cells were mobilized fludarabine, with recombinant human granulocyte colony-stimulating factor and depleted of T-cells using CD34+ cell immunoselection. No post-transplantation graft-versus-host disease (GvHD)prophylaxis was administeredResults Primary engraftment was achieved in 94 of 101 assessable patients. Six of the seven patients who rejected the primary graft, engrafted after a second transplantation. Overall, 100 of 101 patients engrafted. Acute GvHD developed in eight of 100 patients, and chronic GvHD, in five of 70 assessable patients. Thirty-eight patients died of nonleukemic causes. Relapse occurred in nine of 66 patients receiving transplantation in remission and in 17 of 38 receiving transplantation in relapse. Median follow-up of the 40 patients who survived event-free was 22 months (range, 1 to 65 months). Event-free survival (+/- standard deviation) rate was 48 % +/- 8 % and 46 % +/- 10 %, respectively, for the 42 AM L and 24 ALL patients receiving transplantation in remission.Conclusion Our transplantation procedure provides reliable, reproducible CD34+ cell purification, high engraftment rates, and prevention of GvHD. The mismatched-related transplant emerges as a viable, alternative source of stem cells for acute leukemia patients without matched donors and/or those who urgently need transplantation. (c) 2005 by American Society of Clinical Oncology