Slavin S, Weiss L, Ackerstein A, Vourka-Karussis U, Morecki S, Or R, Nagler A, Kapelushnik J, Delukina M, Drakos P
Department of Bone Marrow Transplantation, Hadassah University Hospital, Jerusalem, Israel.
Bone Marrow Transplant. 1993;12 Suppl 3:S54-6.
High, myeloablative doses of chemoradiotherapy represent the treatment of choice for a large number of malignant hematological diseases that cannot be successfully treated with conventional chemotherapy. Residual tumor cells following high dose chemotherapy represent the most common treatment failure, resulting in frequent relapse following autologous bone marrow transplantation (ABMT) and even allogeneic bone marrow transplantation (BMT). Graft vs leukemia (GVL) effects mediated by immunocompetent donor lymphocytes represent a major therapeutic potential of allogeneic BMT which results in reduced rate of relapse, especially when immune interactions between immunocompetent donor's T lymphocytes and host allogantigens is apparent, a reaction which might result in graft vs host disease (GVHD). Recent experiments in animal models of murine leukemias suggest that post-transplant immunotherapy may be successfully accomplished by lymphokine-mediated immunotherapy (LMI) and cell-mediated immunotherapy (CMI). Following allogeneic BMT, provided GVHD can be prevented by T-cell depletion, CMI may be amplified by repeated administration of immunocompetent donor's lymphocytes in graded increments following successful induction of chimerism and sustained hematopoiesis. GVL effects induced by CMI may be further potentiated by in-vivo administration of a short course of recombinant human interleukin-2 (rhIL2). Taken together, our data suggest that post-transplant immunotherapy by cytokines and adoptive cell therapy may successfully prevent relapse in patients at high-risk and even result in complete elimination of tumor cells following overt relapse. Thus, immunotherapy may represent an optimal approach for prevention and treatment of minimal residual disease.
高剂量、清髓性的放化疗是许多无法通过传统化疗成功治疗的恶性血液病的首选治疗方法。高剂量化疗后的残留肿瘤细胞是最常见的治疗失败原因，导致自体骨髓移植（ABMT）甚至异基因骨髓移植（BMT）后频繁复发。具有免疫活性的供体淋巴细胞介导的移植物抗白血病（GVL）效应是异基因BMT的主要治疗潜力，可降低复发率，尤其是当具有免疫活性的供体T淋巴细胞与宿主同种异体抗原之间的免疫相互作用明显时，这种反应可能导致移植物抗宿主病（GVHD）。最近在小鼠白血病动物模型中的实验表明，移植后免疫治疗可以通过细胞因子介导的免疫治疗（LMI）和细胞介导的免疫治疗（CMI）成功完成。在异基因BMT后，如果通过T细胞清除可以预防GVHD，那么在成功诱导嵌合体和持续造血后，通过分级递增重复给予具有免疫活性的供体淋巴细胞，可以增强CMI。通过体内短期给予重组人白细胞介素-2（rhIL2），可以进一步增强CMI诱导的GVL效应。综上所述，我们的数据表明，细胞因子和过继性细胞疗法进行的移植后免疫治疗可能成功预防高危患者复发，甚至在明显复发后完全消除肿瘤细胞。因此，免疫治疗可能是预防和治疗微小残留病的最佳方法。
