Engraftment of allogeneic hematopoietic progenitor cells with purine analog-containing chemotherapy: Harnessing graft-versus-leukemia without myeloablative therapy
Engraftment of allogeneic hematopoietic progenitor cells with purine analog-containing chemotherapy: Harnessing graft-versus-leukemia without myeloablative therapy
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DOI：
10.1182/blood.v89.12.4531
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发表时间：
1997-06-15
期刊：
影响因子：
20.3
通讯作者：
Champlin, R
中科院分区：
文献类型：
--
作者：
Giralt, S;Estey, E;Champlin, R
免疫介导的移植物抗白血病效应对于预防同种异体祖细胞移植后的复发很重要。这个过程需要移植供体的免疫活性细胞。本研究的目的是评估在含有嘌呤类似物的非清髓性化疗后实现同种异体外周血或骨髓祖细胞移植的可行性。由于年龄较大或器官功能障碍而不适合接受常规清髓治疗的晚期白血病或骨髓增生异常综合征（MDS）患者符合资格。所有患者都有 HLA 相同或一种抗原不匹配的相关供体。 15 名患者接受了治疗（13 名患有急性髓性白血病，2 名患有 MDS）。中位年龄为 59 岁（范围为 27 至 71 岁）。 12 名患者要么难以治疗，要么超过首次复发。 8 名患者接受氟达拉滨 30 mg/m(2)/d 治疗 4 天，伊达比星 12 mg/m(2)/d 治疗 3 天，ara-e 2 g/m(2)/d 治疗 4 天 (n = 7) 或美法仑 140 mg/m(2)/d (n = 1)。 7 名患者接受 12 mg/m(2)/d 的 P-氯脱氧腺苷治疗 5 天，并接受 g/m(2)/d 的 ara-C 1 治疗 5 天。 13 名患者接受了同种异体外周血干细胞治疗，1 名患者在化疗后接受了骨髓治疗。移植物抗宿主病（GVHD）预防包括环孢素和甲基泼尼松龙。治疗总体耐受性良好，只有 1 例患者在接受干细胞之前因多器官衰竭死亡。输注后 10 天（范围为 8 至 17 天），13 名患者的中性粒细胞计数中位数超过 0.5 x 10(9)/L。祖细胞输注后 13 天（范围为 7 至 78 天），10 名患者的血小板计数中位数达到 20 x 10(9)/L。八名患者获得完全缓解（骨髓原始细胞
The immune-mediated graft-versus-leukemia effect is important to prevent relapse after allogeneic progenitor cell transplantation. This process requires engraftment of donor immune-competent cells. The objective of this study was to assess the feasibility of achieving engraftment of allogeneic peripheral blood or bone marrow progenitor cell after purine analog containing nonmyeloablative chemotherapy. Patients with advanced leukemia or myelodysplastic syndromes (MDS) who were not candidates for a conventional myeloablative therapy because of older age or organ dysfunction were eligible. All patients had an HLA-identical or one-antigen-mismatched related donor. Fifteen patients were treated (13 with acute myeloid leukemia and 2 with MDS). The median age was 59 years (range, 27 to 71 years). Twelve patients were either refractory to therapy or beyond first relapse. Eight patients received fludarabine at 30 mg/m(2)/d for 4 days with idarubicin at 12 mg/m(2)/d for 3 days and ara-e at 2 g/m(2)/d for 4 days (n = 7) or melphalan at 140 mg/m(2)/d (n = 1). Seven patients received P-chloro-deoxyadenosine at 12 mg/m(2)/d for 5 days and ara-C 1 at g/m(2)/d for 5 days. Thirteen patients received allogeneic peripheral blood stem cells and 1 received bone marrow after chemotherapy. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and methyl-prednisolone. Treatment was generally well tolerated, with only 1 death from multiorgan failure before receiving stem cells. Thirteen patients achieved a neutrophil count of greater than 0.5 x 10(9)/L a median of 10 days postinfusion (range, 8 to 17 days). Ten patients achieved platelet counts of 20 x 10(9)/L a median of 13 days after progenitor cell infusion (range, 7 to 78 days). Eight patients achieved complete remissions (bone marrow blasts were