Current problems and future goals in clinical bone marrow transplantation

Allogeneic bone marrow transplantation (BMT) is associated with the cumulative toxicity of high dose chemotherapy and/or radiation therapy regimens currently in use, with acute and chronic graft vs host disease (GVHD), as well as with the consequences of delayed immunological reconstitution due to slow maturation of the immune system and drugs currently used for prevention of GVHD. Although GVHD may be overcome by T-cell depletion it leads to an increased incidence of graft rejection and relapse of the original malignancy. These too represent major problems. Autologous BMT results in high relapse rates due to lack of immune-mediated allogeneic interactions of grafted cells against tumor cells of the host. In view of the fact that experiments in animal models of human disease suggest that antileukemic effects of allogeneic marrow grafts may be partially independent of GVHD, new approaches for amplification of antitumor effects of autologous and allogeneic cells by cytokines and by lymphokine-activated cells are discussed. Evidence for antileukemia effects of IL-2 therapy in animals is presented. Beneficial effects of several cytokines in autologous and allogeneic BMT are suggested by significant facilitation of immunological and hematopoietic reconstitution following transplantation of bone marrow cells treated in vitro with cytokines (including ASTA-Z-purged marrow) and following in vivo administration of cytokines in conjunction with BMT. Overall, in view of several innovative biological interventions, it seems that significant progress in autologous and allogeneic BMT may be underway; the concept yet to be established is that successful and less risky BMT may be accomplished by replacing aggressive chemoradiotherapy regimens with sophisticated immunomanipulations and biological response modifying agents.