The prophylactic potential of fludarabine monophosphate in graft-versus-host disease after bone marrow transplantation in murine models

Fludarabine phosphate, a purine analogue currently used in the therapy of h ematological malignancies, is known to cause immunosuppression and long-las ting T cell lymphopenia, Tn this study, the effect of fludarabine on murine graft-versus-host disease occurring after marrow transplantation across ma jor and minor histocompatibility barriers was evaluated, Survival of (BALB/ c x C57BL/6)F1 mice irradiated and transplanted across the major histocompa tibility barrier with C57BL/6 spleen cells, and subsequently treated with f ludarabine was significantly longer than that of the control animals (P < 0 .0001). On the other hand, fludarabine had no effect on the graft-versus-ho st disease and survival of CBA mice transplanted by B10.BR and of BALB/c mi ce transplanted by B10.D2 spleen cells across the minor histocompatability barrier. The results indicate that in certain murine models, particularly a major mismatch, fludarabine has the potential to induce bilateral toleranc e and stable chimerism after marrow transplantation.