Effect of deoxyspergualin on graft-versus-host disease and graft- versus-leukemia in mice.
The effect of 15-deoxyspergualin (DSG) on bone marrow (BM) engraftment and graft-versus-host disease (GVHD) was studied in mice across both major (MHC) and minor (MiHC) histocompatibility barriers. (BALB/c x C57BL/6)F1 mice were inoculated with C57BL/6 cells, CBA mice were given B10.BR cells and BALB/c mice were transplanted with B10.D2 cells. All recipient mice were irradiated lethally or sublethally prior to transplantation. DSG had no effect on engraftment of parental cells in F1 mice at both 2.5 mg/kg and 10 mg/kg given daily for 10 days after treatment. Survival of F1 recipients of C57BL/6 cells increased significantly with 2.5 mg/kg DSG (p < 0.05). Across MiHC, 75% of DSG-treated CBA mice survived transplant for more than 150 days. No effect on GVHD was observed in the B10.D2 --> BALB/c setting. DSG abolished graft-versus-leukemia (GVL) effects in F1 mice transplanted with both BM and spleen cells (20%) of C57BL/6 mice and additionally inoculated with B cell leukemia (BCL1). In summary, in the semi-allogeneic murine models presented here DSG prevented GVHD but at the same time suppressed GVL effects induced by the allograft. For clinical use, DSG might therefore be very useful for prevention of GVHD post-allogeneic bone marrow transplantation for non-malignant diseases or for leukemia.
Weiss
L
L
Department of Bone Marrow Transplantation, Hadassah University Hospital, Jerusalem, Israel.
Reich
S
S
Slavin
S
S
D000818:Animals; D016026:Bone Marrow Transplantation / Q000009:adverse effects* / Q000276:immunology; D006085:Graft Survival / Q000187:drug effects; D006086:Graft vs Host Disease / Q000517:prevention & control*; D006146:Guanidines / Q000494:pharmacology*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D015448:Leukemia, B-Cell / Q000276:immunology / Q000628:therapy; D007942:Leukemia, Experimental / Q000276:immunology / Q000628:therapy*; D008212:Lymphocyte Depletion; D008285:Major Histocompatibility Complex; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D015778:Minor Histocompatibility Antigens; D013601:T-Lymphocytes / Q000276:immunology; D014184:Transplantation, Homologous
D006146:Guanidines; D007166:Immunosuppressive Agents; D015778:Minor Histocompatibility Antigens; C037258:gusperimus