Pretransplant conditioning with busulfan (myleran) and cyclophosphamide for nonmalignant diseases: Assessment of engraftment following histocompatible allogeneic bone marrow transplantation

Four pediatric patients with diseases potentially curable by bone marrow transplantation (BMT)³—i.e., common variable immune deficiency, Wiskott-Aldrich Syndrome (WAS), mucopolysaccharidosis type VI, and mucopolysaccharidosis type I received a conditioning regimen consisting of busulfan and cyclophosphamide prior to BMT from HLA-identical, mixed leukocyte culture (MLC)-unreactive siblings. Only one of the four patients achieved full engraftment. Of the remaining three patients, one experienced failure of engraftment, and two had persistent mixed chimerism. Although no serious complications were directly related to the preparative therapy, the doses of busulfan and cyclophosphamide previously described to be adequate for conditioning children with WAS were completely effective in only one of three pediatric patients in this series. Despite a higher dose of busulfan (16 mg/kg), mixed chimerism was observed in a subsequent patient. Of 13 evaluable patients in the literature in whom busulfan and cyclophosphamide had been used as preconditioning regimens for a variety of nonmalignant conditions, eight demonstrated lack of complete and sustained engraftment. On the other hand, clinical improvement has accompanied partial engraftment in some cases. We conclude that additional immunosuppressive and/or myeloablative conditioning is necessary if complete engraftment is attempted in histocompatible allogeneic BMT for many of the nonmalignant disorders.