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Thalidomide does not interfere with graft-versus-leukemia reactivity in mice

Department of Bone Marrow Transplantation and Cancer Immunobiology Research Laboratory, Hadassah University Hospital, Jerusalem, Israel

Lola Weiss, PhD

Department of Bone Marrow Transplantation and Cancer Immunobiology Research Laboratory, Hadassah University Hospital, Jerusalem, Israel

Orit Pappo, MD

Department of Pathology, Hebrew University-Hadassah Medical School and Hadassah University Hospital, Jerusalem, Israel

Eliezer Okon, MD

Department of Pathology, Hebrew University-Hadassah Medical School and Hadassah University Hospital, Jerusalem, Israel

Reuven Or, MD

Department of Bone Marrow Transplantation and Cancer Immunobiology Research Laboratory, Hadassah University Hospital, Jerusalem, Israel

Objective. To determine whether thalidomide is an effective prophylactic agent against acute graft-versus-host disease (GVHD) and whether it exerts an effect on graft-versus-leukemia (GVL) reactivity, the drug was administered to leukemic mice that were exposed to allogeneic bone marrow transplantation.

Methods. Mice (BALB/c 3 C57BL/6) F₁ were inoculated with 10⁷ B cell leukemia cells (BCL1) and conditioned with total body irradiation followed by reconstitution with bone marrow plus splenic cells harvested from C57BL/6 mice. After transplant, mice were treated with oral thalidomide (20 mg/kg/day) for a period of 10 days.

Results. Stable chimerism was documented in all recipients with $73% (mean) donor-type C57 cells. In this semi-allogeneic murine model, thalidomide failed to prevent or alleviate the acute GVHD symptoms; however, the drug did not impair GVL reactivity. The antileukemia allogeneic effect was similar in the thalidomide and non-thalidomide-treated animals. Comparison of the GVL reactivity occurring in the allogeneically transplanted groups with that in the syngeneic recipients revealed a significant difference (P 5 0.001).

Conclusions. Although thalidomide did not exert any effect against acute GVHD, the fact that the GVL reactivity was spared holds promise for its use as a treatment modality in chronic GVHD.

Key Words: Thalidomide • graft-versus-host disease • graft-versus-leukemia reactivity • bone marrow transplantation • mice

Journal of Oncology Pharmacy Practice, Vol. 5, No. 4, 179-183 (1999)
DOI: 10.1177/107815529900500403


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