Protective conditioning for acute graft-versus-host disease
Protective conditioning for acute graft-versus-host disease
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DOI：
10.1056/nejmoa050642
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发表时间：
2005-09-29
影响因子：
158.5
通讯作者：
Strober, S
中科院分区：
文献类型：
--
作者：
Lowsky, R;Takahashi, T;Strober, S
背景：全淋巴照射加抗胸腺细胞血清可以保护小鼠在造血细胞移植后免受急性移植物抗宿主病（GVHD）的影响。我们在人体中测试了这一策略。 方法：37 名患有淋巴恶性疾病或急性白血病的患者接受了实验性调理方案，其中包括 10 剂全淋巴照射（每次 80 cGy）加抗胸腺细胞球蛋白，然后输注来自相关或无关捐献者的 HLA 匹配外周血单核细胞。 结果：37例移植受者中，仅有2例在造血细胞移植后出现急性GVHD。从部分缓解到完全缓解的变化显示了对淋巴恶性疾病患者的有效抗肿瘤作用。在接受全淋巴照射和抗胸腺细胞球蛋白调理的移植受者中，与正常对照受试者和接受单剂量全身照射的对照受试者相比，在体外刺激后产生白细胞介素4的供体CD4+T细胞的比例增加了五倍，并且体外对同种异体抗原的增殖反应降低（200 结论：全淋巴照射加抗胸腺细胞球蛋白的治疗方案可降低急性 GVHD 的发生率，并允许接受造血细胞移植治疗的淋巴恶性疾病或急性白血病患者具有移植物抗肿瘤活性。
BACKGROUND:Conditioning with total lymphoid irradiation plus antithymocyte serum protects mice against acute graft-versus-host disease (GVHD) after hematopoietic-cell transplantation. We tested this strategy in humans.METHODS:Thirty-seven patients with lymphoid malignant diseases or acute leukemia underwent an experimental conditioning regimen with 10 doses of total lymphoid irradiation (80 cGy each) plus antithymocyte globulin, followed by an infusion of HLA-matched peripheral-blood mononuclear cells from related or unrelated donors who received granulocyte colony-stimulating factor.RESULTS:Of the 37 transplant recipients, only 2 had acute GVHD after hematopoietic-cell transplantation. Potent antitumor effects in patients with lymphoid malignant diseases were shown by the change from partial to complete remission. In the transplant recipients who underwent conditioning with total lymphoid irradiation and antithymocyte globulin, the fraction of donor CD4+ T cells that produced interleukin-4 after in vitro stimulation increased by a factor of five, and the proliferative response to alloantigens in vitro was reduced, as compared with normal control subjects and control subjects who underwent conditioning with a single dose of total-body irradiation (200 cGy).CONCLUSIONS:A regimen of total lymphoid irradiation plus antithymocyte globulin decreases the incidence of acute GVHD and allows graft antitumor activity in patients with lymphoid malignant diseases or acute leukemia treated with hematopoietic-cell transplantation.