Selective depletion of CD8+ T lymphocytes for prevention of graft-versus-host disease after allogeneic bone marrow transplantation.

Selective depletion of CD8+ T lymphocytes for prevention of graft-versus-host disease after allogeneic bone marrow transplantation.
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DOI:
10.1182/blood.v76.2.418.bloodjournal762418
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发表时间:
1990-07
期刊:
影响因子:
20.3
通讯作者:
R. Champlin;W. Ho;J. Gajewski;S. Feig;M. Burnison;G. Holley;P. Greenberg;Kyoung Lee;I. Schmid;J. Giorgi
R. Champlin;W. Ho;J. Gajewski;S. Feig;M. Burnison;G. Holley;P. Greenberg;Kyoung Lee;I. Schmid;J. Giorgi
中科院分区:
医学1区
文献类型:
--
作者:
R. Champlin;W. Ho;J. Gajewski;S. Feig;M. Burnison;G. Holley;P. Greenberg;Kyoung Lee;I. Schmid;J. Giorgi

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在36例接受HLA相合同胞移植治疗白血病的患者中,评估了从供体骨髓中选择性耗竭CD 8+细胞的效果。供体骨髓使用抗Leu-2单克隆抗体和补体进行离体处理。患者在移植后接受环孢素治疗6个月。33例患者进行了初始植入。3例血液学恢复失败,1例初次植活的患者晚期移植物衰竭。大于或等于2级急性移植物抗宿主病的精算发生率为28% +/- 18%,通常局限于皮肤。在33例植入患者中,32例为完全嵌合体,1例为混合嵌合体。血液学和免疫学恢复的克里思与未修饰骨髓移植报告的速度相当,尽管CD 4+和CD 8 + T细胞恢复的速度相当。白血病复发率为11% ± 10%,发生在3例急性白血病患者中,但13例慢性粒细胞白血病移植患者中无复发。2年时的精算生存率为57% +/- 17%。这些数据表明,在移植去除CD 8+细胞的骨髓后,通常会发生迅速的血液学和免疫学恢复的植入,急性移植物抗宿主病的发生率相对较低。移植失败仍然是一个问题,尽管保留的CD 4+细胞在供体骨髓。慢性粒细胞性白血病患者白血病复发的缺乏提示移植物抗白血病效应的保留,至少对于这种恶性肿瘤是这样。
The effects of selectively depleting CD8+ cells from donor bone marrow were assessed in 36 patients receiving transplantation from an HLA-identical sibling as treatment for leukemia. Donor bone marrow underwent ex vivo treatment using anti-Leu-2 monoclonal antibody and complement. Patients received cyclosporine post-transplant for 6 months. Thirty-three patients had initial engraftment. Three failed to have hematologic recovery, and one patient with initial engraftment had late graft failure. The actuarial incidence of grade greater than or equal to 2 acute graft-versus-host disease was 28% +/- 18% and was usually confined to the skin. Of 33 patients with engraftment, 32 were complete chimeras and one had mixed chimerism. The tempo of hematologic and immunologic recovery was comparable with that reported with transplantation of unmodified bone marrow, although CD4+ and CD8+ T cells recovered at comparable rates. The actuarial rate of leukemia relapse was 11% +/- 10%, occurring in three patients with acute leukemia but in none of 13 patients transplanted for chronic myelogenous leukemia. Actuarial survival was 57% +/- 17% at 2 years. These data indicate that after transplantation of marrow depleted of CD8+ cells, engraftment with prompt hematologic and immunologic recovery generally occurs, with a relatively low rate of acute graft-versus-host disease. Graft failure remains a problem despite retention of CD4+ cells within the donor marrow. The lack of leukemia relapse in patients with chronic myelogenous leukemia suggests retention of a graft-versus-leukemia effect, at least for this malignancy.