Horowitz M M, Gale R P, Sondel P M, Goldman J M, Kersey J, Kolb H J, Rimm A A, Ringdén O, Rozman C, Speck B
Division of Hematology/Oncology, Medical College of Wisconsin, Milwaukee 53226.
Blood. 1990 Feb 1;75(3):555-62.
To determine whether graft-versus-leukemia (GVL) reactions are important in preventing leukemia recurrence after bone marrow transplantation, we studied 2,254 persons receiving HLA-identical sibling bone marrow transplants for acute myelogenous leukemia (AML) in first remission, acute lymphoblastic leukemia (ALL) in first remission, and chronic myelogenous leukemia (CML) in first chronic phase. Four groups were investigated in detail: recipients of non--T-cell depleted allografts without graft-versus-host disease (GVHD), recipients of non--T-cell depleted allografts with GVHD, recipients of T-cell depleted allografts, and recipients of genetically identical twin transplants. Decreased relapse was observed in recipients of non--T-cell depleted allografts with acute (relative risk 0.68, P = .03), chronic (relative risk 0.43, P = .01), and both acute and chronic GVDH (relative risk 0.33, P = .0001) as compared with recipients of non--T-cell depleted allografts without GVHD. These data support an antileukemia effect of GVHD. AML patients who received identical twin transplants had an increased probability of relapse (relative risk 2.58, P = .008) compared with allograft recipients without GVHD. These data support an antileukemia effect of allogeneic grafts independent of GVHD. CML patients who received T-cell depleted transplants with or without GVHD had higher probabilities of relapse (relative risks 4.45 and 6.91, respectively, P = .0001) than recipients of non--T-cell depleted allografts without GVHD. These data support an antileukemia effect independent of GVHD that is altered by T-cell depletion. These results explain the efficacy of allogeneic bone marrow transplantation in eradicating leukemia, provide evidence for a role of the immune system in controlling human cancers, and suggest future directions to improve leukemia therapy.
为了确定移植物抗白血病（GVL）反应在预防骨髓移植后白血病复发中是否重要，我们研究了2254例接受HLA相同同胞骨髓移植的患者，这些患者分别处于急性髓性白血病（AML）首次缓解期、急性淋巴细胞白血病（ALL）首次缓解期以及慢性髓性白血病（CML）慢性期。详细研究了四组患者：未发生移植物抗宿主病（GVHD）的非T细胞去除同种异体移植受者、发生GVHD的非T细胞去除同种异体移植受者、T细胞去除同种异体移植受者以及基因相同的双胞胎移植受者。与未发生GVHD的非T细胞去除同种异体移植受者相比，发生急性GVHD（相对风险0.68，P = 0.03）、慢性GVHD（相对风险0.43，P = 0.01）以及急慢性GVHD（相对风险0.33，P = 0.0001）的非T细胞去除同种异体移植受者复发率降低。这些数据支持GVHD的抗白血病作用。与未发生GVHD的同种异体移植受者相比，接受同卵双胞胎移植的AML患者复发概率增加（相对风险2.58，P = 0.008）。这些数据支持不依赖GVHD的同种异体移植物的抗白血病作用。接受T细胞去除移植（无论是否发生GVHD）的CML患者复发概率高于未发生GVHD的非T细胞去除同种异体移植受者（相对风险分别为4.45和6.91，P = 0.0001）。这些数据支持不依赖GVHD的抗白血病作用，且该作用会因T细胞去除而改变。这些结果解释了同种异体骨髓移植在根除白血病方面的疗效，为免疫系统在控制人类癌症中的作用提供了证据，并为改善白血病治疗提出了未来方向。
