Graft-versus-host disease prevention in allogeneic bone marrow transplantation from histocompatible siblings. A pilot study using immunotoxins for T cell depletion of donor bone marrow.
Graft-versus-host disease prevention in allogeneic bone marrow transplantation from histocompatible siblings. A pilot study using immunotoxins for T cell depletion of donor bone marrow.
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组织相容性兄弟姐妹同种异体骨髓移植中移植物抗宿主病的预防。
DOI：
10.1097/00007890-198707000-00015
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发表时间：
1987
期刊：
影响因子：
6.2
通讯作者：
Kersey,JH
中科院分区：
文献类型：
--
作者：
Filipovich,AH;Vallera,DA;Youle,RJ;Haake,R;Blazar,BR;Arthur,D;NevilleJr,DM;Ramsay,NK;McGlave,P;Kersey,JH
年龄在 7-53 岁的 17 名患者接受了组织相容性骨髓移植，这些骨髓已通过离体免疫毒素 (IT) 治疗耗尽了 T 淋巴细胞。 12 名患者患有高危急性白血病，5 名患者患有慢性粒细胞白血病。未使用其他移植物抗宿主病（GVHD）预防措施。本研究使用了三种与蓖麻毒素缀合的抗 T 细胞单克隆抗体的混合物：TA-1、UCHT-1（抗 CD3）和 T101（抗 CD5）。输注的骨髓细胞的平均数量为1.5×10 8 个单核细胞/kg受体体重。 17 名患者中有 13 名表现出完全且持续的植入。四名患者经历了自体骨髓恢复和/或移植物排斥。与接受单独甲氨蝶呤或甲氨蝶呤联合甲氨蝶呤和泼尼松加抗胸腺细胞球蛋白（ATG）或OKT3的GVHD预防的白血病患者历史组相比，稳定植入的IT患者表现出连续三天白细胞恢复≥1000mm 3 的时间更短（中位数，20天与26天，P=.03）。对于 IT 治疗组和历史对照组的患者来说，第 28 天时总淋巴细胞、B 和 T 细胞亚群以及 T 细胞功能的恢复情况差异很大，但相似。 4 名患者（年龄分别为 13、18、21 和 38 岁）出现 II 级皮肤 GVHD，但没有人出现严重 GVHD。 13 名持久植入的患者中有 8 名出现移植后白血病复发。目前仅四名患者还活着；两名患者在移植后没有复发，另外两名患者在移植后复发后病情得到缓解。我们的结论是，在本次小系列研究中，通过去除体外 T 细胞来预防 GVHD，并未观察到严重的 GVHD，并且对于持续初次移植的病例，血液学和淋巴细胞功能得到了良好的恢复。需要进行更大规模的随机对照研究来确定用 IT 去除供体骨髓的 T 细胞是否可以显着降低 GVHD 和/或提高无病生存率。
Seventeen patients, ages 7–53 years were transplanted with histocompatible bone marrow that had been depleted of T lymphocytes by ex vivo immunotoxin (IT) treatment. Twelve patients had high-risk acute leukemias, and five had chronic myelogenous leukemia. No other graft-vs.-host disease (GVHD) prophylaxis was used. A mixture of three anti-T-cell monoclonal antibodies conjugated to ricin were used in this study: TA-1, UCHT-1 (anti-CD3), and T101 (anti-CD5). The mean number of bone marrow cells infused was 1.5× 10 8 mononuclear cells/kg recipient weight. Thirteen of the 17 patients demonstrated complete and sustained engraftment. Four patients experienced autologous marrow recovery and/or graft rejection. Compared with an historical group of leukemic patients who received GVHD prophylaxis with methotrexate alone or combinations of methotrexate, and prednisone plus antithymocyte globulin,(ATG) or OKT3, the IT patients with stable engraftment demonstrated shorter time to recovery of leukocytes≥ 1000mm 3 for three consecutive days (median, 20 days vs. 26 days, P=. 03). The recovery of total lymphocytes, B and T cell subsets, and T cell function by day 28 was highly variable, but similar, for patients in both the IT-treated group and historical controls. Four patients (ages 13, 18, 21, and 38) developed grade II skin GVHD, but none had severe GVHD. Eight of the 13 patients with durable engraftment have had posttransplant leukemie relapse. Currently only four patients remain alive; two have not relapsed posttransplant, while the other two achieved remission following posttransplant relapse. We conclude that severe GVHD was not observed in this small series with ex vivo T cell depletion for GVHD prophylaxis, and that favorable recovery of hematologic and lymphocytic function was demonstrated for cases where primary engraftment was sustained. A larger randomized controlled study will be needed to establish whether T cell depletion of donor bone marrow with IT can significantly reduce GVHD, and/or improve disease-free survival.