The graft-vs-leukemia reaction (GvLR) and interleukin-2 (IL-2) after allogeneic bone marrow transplantation (BMT): preclinical studies (Meeting abstract).

Important note: Information in this article was accurate in 1993. The state of the art may have changed since the publication date.

The graft-vs-leukemia reaction (GvLR) and interleukin-2 (IL-2) after allogeneic bone marrow transplantation (BMT): preclinical studies (Meeting abstract).

Exp Hematol; 20(6):721 1992. Unique Identifier : AIDSLINE ICDB/93688165
Kloosterman TC; Martens AC; van Bekkum DW; Hagenbeek A; Inst. of Applied Radiobiology and Immunology TNO, Rijswijk, The; Netherlands

Abstract: Relapse remains the major problem in the treatment of leukemia with BMT. Allogeneic BMT with or without clinical signs of graft-vs-host disease (GvHD) is correlated with a lower relapse rate, as compared with autologous BMT, while T-cell depletion of the graft results in a higher relapse rate. Thus, GvHD is accompanied by a T-cell-mediated GvLR, which may prevent a leukemia relapse. In two nonimmunogenic rat leukemia models (ie, the brown Norway acute myelocytic leukemia and the acute lymphoblastic L4415-leukemia in the WAG/Rij rat), full-blown leukemia is treated with total-body irradiation, with or without cyclophosphamide, to induce 'minimal residual disease.' Subsequently, the GvLR is studied using syngeneic, allogeneic or semiallogeneic BMT, with and without addition of graded numbers of lymphocytes. Neither syngeneic nor semiallogeneic (hybrid to parental strains) BMT resulted in antileukemic effects, whereas in allogeneic BMT the BMT-graft, with a critical number of additional splenocytes, results in a small but significant GvLR (1- to 2-log leukemic cell kill). These results appear to be very similar to the clinical experience. Addition of more allogeneic splenocytes induces a lethal acute GvHD. T-cell depletion experiments indicate that both CD4- and CD8-positive cells are important in inducing GvHD. Semiallogeneic (parental to hybrid strains) BMT showed that the GvLR in both leukemia models studied are merely alloeffects. IL-2 therapy after allogeneic BMT resulted in increased antileukemic effects and acute lethal GvHD when low and high doses were administered, respectively. Further IL-2 dose-finding studies reveal whether a GvLR can be optimized without an increased risk of (lethal) GvHD.

Keywords: Animal *Bone Marrow Transplantation CD4-CD8 Ratio *Graft vs Host Reaction Interleukin-2/*THERAPEUTIC USE Leukemia, Experimental/PATHOLOGY/*SURGERY/THERAPY Lymphocyte Depletion Neoplasm Recurrence, Local T-Lymphocytes Transplantation, Homologous ABSTRACT
930330
M9331099

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