PREVENTION AND TREATMENT OF RELAPSE BY BONE-MARROW TRANSPLANTATION

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. Residu al tumor cells following high dose chemotherapy represent the most com men treatment failure, resulting in frequent relapse following autolog ous bone marrow transplantation (ABMT) and even allogeneic bone marrow transplantation (BMT). Graft vs leukemia (GVL) effects mediated by im munocompetent donor lymphocytes represent a major therapeutic potentia l of allogeneic BMT which results in reduced rate of relapse, especial ly when immune interactions between immunocompetent donor's T lymphocy tes and host allogantigens is apparent, a reaction which might result in graft vs host disease (GVHD). Recent experiments in animal models o f murine leukemias suggest that post-transplant immunotherapy may be s uccessfully accomplished by lymphokine-mediated immunotherapy (LMI) an d cell-mediated immunotherapy (CMI). Following allogeneic BMT, provide d GVHD can be prevented by T-cell depletion, CMI may be amplified by r epeated administration of immunocompetent donor's lymphocytes in grade d 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 inter leukin-2 (rhIL2). Taken together, our data suggest that post-transplan t immunotherapy by cytokines and adoptive cell therapy may successfull y prevent relapse in patients at high-risk and even result in complete elimination of tumor cells following overt relapse. Thus, immunothera py may represent an optimal approach for prevention and treatment of m inimal residual disease.