![]() ![]() We found that 2 Gy TBI either without postgrafting immunosuppression or with monotherapy using cyclosporine (CSP) did not enable consistently sustained engraftment. ![]() We used a canine model of major histocompatibility complex (MHC=DLA)-matched marrow grafts to develop a minimal-intensity or NMA conditioning regimen. This review will describe the preclinical basis for some of the RIC and NMA regimens, address GVT effects, summarize trial results with HLA-matched and mismatched grafts, address the use of older sibling donors, and explore ways to reduce the risks of GVHD and relapse. Forman SJ, Negrin RS, Antin JH, and Appelbaum FR, Eds., ©John Wiley & Sons, Ltd., in press. Reduced-intensity allogeneic transplantation regimens, Chapter 21, In: Thomas’ Hematopoietic Cell Transplantation, 5 th Edition. These are non-relapse mortality (NRM), mainly related to concurrent or preceding graft- vs.-host disease (GVHD) and its treatment, and relapse mortality.įigure 1. However, all the trials share two major problems that have limited trial outcomes. The results of trials using RIC or nonmyeloablative (NMA) regimens have been surprisingly encouraging. The choice of a given regimen may, in part, be dictated by the nature of the underlying malignancy and, in part, by comorbidities. The relative intensities of individual conditioning regimens vary considerably as far as their immunosuppressive and myelosuppressive properties are concerned ( Figure 1). The markedly reduced toxicities associated with these novel regimens have allowed for the extension of allogeneic HCT to include older and medically infirm patients. Such regimens need to be immunosuppressive enough to allow sustained engraftment, thereby enabling GVT effects. The finding that the cure of hematologic malignancies not only results from intense conditioning but also in large part from the killing of tumor cells by transplanted donor immune cells, termed “graft- vs.-tumor” (GVT) effect, set the stage for the development of reduced-intensity conditioning (RIC) regimens. acute myelocytic leukemia (AML) or non-Hodgkin lymphoma (NHL), range from 65 to 75 years. This has been unfortunate, given that the median ages of patients at the time of diagnosis of most candidate malignancies, e.g. The high intensity of the traditional regimens has precluded using allogeneic HCT in older patients or those with comorbidities because of unacceptable toxicities. The dual purpose of conditioning has been to reduce the patients’ burden of malignant cells before HCT and suppress their immune system so that the allogeneic grafts are not rejected. This review summarizes the encouraging early results seen with the new regimens and discusses the two hurdles that need to be overcome for achieving even greater success, disease relapse and graft- versus-host disease.Ĭonditioning for allogeneic hematopoietic cell transplantation (HCT) in the treatment of hematologic malignancies has traditionally involved high doses of total body irradiation (TBI) and/or chemotherapy. These regimens enabled allogeneic engraftment, thereby setting the stage for graft- versus-tumor effects. The finding that many of the cures achieved with allogeneic hematopoietic transplantation were due to graft- versus-tumor effects led to the development of less toxic and well-tolerated reduced intensity and nonmyeloablative regimens. Until recently these patients and those with comorbidities were not candidates for treatment with allogeneic hematopoietic transplantation because they were unable to tolerate the heretofore used high-dose conditioning regimens. Most hematological malignancies occur in older patients. ![]()
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