GRAFT FAILURE IN CHILDREN RECEIVING HLA-MISMATCHED MARROW TRANSPLANTSWITH BUSULFAN-CONTAINING REGIMENS

Identifying risk factors that lead to graft failure may reduce morbidi ty and mortality after bone marrow transplantation (BMT) for hematolog ic malignancies. We evaluated engraftment of all patients with acute m yelogenous leukemia (AML), chronic myelogenous leukemia (CML) and myel odysplastic syndrome (MDS) receiving an unmanipulated marrow allogenei c BMT at the Detroit Medical Center from 1987 to 1992 using a busulfan , cyclophosphamide +/- cytarabine preparative regimen. Three of 118 pa tients had graft failure (2.5%; (95% confidence interval (CI) 0.7%, 6. 4%). Graft failure was high in patients less than or equal to 15 years with 3 of 12 patients with failure (25.0%) compared with 0 of 106 pat ients > 15 years (p = 0.002). Failure to engraft was not seen in HLA-i dentical (related or unrelated) donor transplants (0 of 103) whereas 3 of 15 HLA-mismatched donors failed (p = 0.003). Patient diagnosis, lo cus of HLA-mismatch, cytarabine in the preparative regimen, marrow cel l dose and the relative reactive index (RRI) were not significant fact ors. Altered busulfan kinetics secondary to young age was probably not a major factor since 8 of 8 HLA-identical donor transplants engrafted in children. These findings demonstrate that patients receiving an un manipulated marrow graft using busulfan-containing regimens were at a high risk for graft failure only if they were less than or equal to 15 years of age and had an HLA-mismatched donor. More immunosuppressive preparative regimens, possibly including total body irradiation, shoul d be considered to prevent potential graft failure in children.