title: Graft failure in children receiving HLA-mismatched marrow transplants with busulfan-containing regimens.
abstract: Identifying risk factors that lead to graft failure may reduce morbidity and mortality after bone marrow transplantation (BMT) for hematologic malignancies. We evaluated engraftment of all patients with acute myelogenous leukemia (AML), chronic myelogenous leukemia (CML) and myelodysplastic syndrome (MDS) receiving an unmanipulated marrow allogeneic BMT at the Detroit Medical Center from 1987 to 1992 using a busulfan, cyclophosphamide +/- cytarabine preparative regimen. Three of 118 patients had graft failure (2.5%; (95% confidence interval (CI) 0.7%, 6.4%). Graft failure was high in patients < or = 15 years with 3 of 12 patients with failure (25.0%) compared with 0 of 106 patients > 15 years (p = 0.002). Failure to engraft was not seen in HLA-identical (related or unrelated) donor transplants (0 of 103) whereas 3 of 15 HLA-mismatched donors failed (p = 0.003). Patient diagnosis, locus of HLA-mismatch, cytarabine in the preparative regimen, marrow cell dose and the relative reactive index (RRI) were not significant factors. 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 unmanipulated marrow graft using busulfan-containing regimens were at a high risk for graft failure only if they were < or = 15 years of age and had an HLA-mismatched donor. More immunosuppressive preparative regimens, possibly including total body irradiation, should be considered to prevent potential graft failure in children.
authors.affiliation: Detroit Medical Center Bone Marrow Transplantation Program: Department of Pediatrics, Wayne State University.
authors.forename: K R
authors.initials: KR
authors.lastname: Schultz
authors.forename: V
authors.initials: V
authors.lastname: Ratanatharathorn
authors.forename: E
authors.initials: E
authors.lastname: Abella
authors.forename: A B
authors.initials: AB
authors.lastname: Eisenbrey
authors.forename: C
authors.initials: C
authors.lastname: Karanes
authors.forename: L G
authors.initials: LG
authors.lastname: Lum
authors.forename: M M
authors.initials: MM
authors.lastname: de Planque
authors.forename: J P
authors.initials: JP
authors.lastname: Uberti
authors.forename: Y
authors.initials: Y
authors.lastname: Ravindranath
authors.forename: L L
authors.initials: LL
authors.lastname: Sensenbrenner
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D016026:Bone Marrow Transplantation / Q000009:adverse effects / Q000276:immunology*; D002066:Busulfan / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D016572:Cyclosporine / Q000627:therapeutic use; D003561:Cytarabine / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D006084:Graft Rejection / Q000453:epidemiology* / Q000209:etiology / Q000517:prevention & control; D006680:HLA Antigens / Q000276:immunology*; D006648:Histocompatibility / Q000276:immunology*; D006801:Humans; D015994:Incidence; D015470:Leukemia, Myeloid, Acute / Q000628:therapy; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000628:therapy; D012307:Risk Factors; D014019:Tissue Donors
chemical_list: D006680:HLA Antigens; D003561:Cytarabine; D016572:Cyclosporine; D002066:Busulfan