Comparison of the lymphoid toxicities of mitobronitol and busulphan in mice: reduced B cell toxicity and improved thymic recovery as possible contributors to the reduced risk for complications following BMT with mitobronitol preconditioning

Abstract

It has previously been reported that the use of mitobronitol (dibromomannitol, DBM) instead of busulphan (BU) for myelosuppression is associated with significantly decreased risk for several complications of allogeneic bone marrow transplantation in accelerated chronic granulocytic leukemia. In exploring the pharmacologic basis for this observation, we have compared the acute and subacute cytotoxicities of DBM and BU on the spleen and thymus of mice. While there was comparable early (day 3) weight loss in both organs following these treatments, splenic B cells exhibited significantly less damage, and thymic regeneration (over weeks) was significantly faster following DBM treatment than with BU. These observations raise the possibility that improved post-BMT immune recovery could contribute to the clinical benefits observed with DBM-preconditioning.