title: Children with acute lymphoblastic leukemia who receive T-cell-depleted HLA mismatched marrow allografts from unrelated donors have an increased incidence of primary graft failure but a similar overall transplant outcome.
abstract: Disparity for HLA in unrelated donor bone marrow transplantation (BMT) increases the risk of graft rejection and graft-versus-host disease (GVHD) and may compromise transplant outcome. We have compared the outcome of matched and mismatched transplants from unrelated donors in 137 children with acute lymphoblastic leukemia (ALL). Their disease status was complete remission (CR)-1, 24 patients; CR-2, 88 patients; CR-3, 18 patients; CR-4, 2 patients; and relapse, 5 patients. CAMPATH monoclonal antibodies were used for T-cell depletion and cyclosporin A was given to 134 children together with short-course methotrexate in 43, mainly when there was HLA disparity. Fifty-two donor/recipient pairs were HLA-mismatched, 41 at HLA-A and -B and 11 at HLA-DR and -DQ loci. Overall graft failure was increased in recipients of marrow mismatched at either HLA-A, -B, -DR, or -DQ (15.7% v 4.8%; P =.057) mainly because there was a higher proportion of children with primary graft failure (11. 8% v 1.2%; P =.012). The presence of an HLA-C locus mismatch did not independently increase the likelihood of graft failure. There was no significant difference in the incidence of acute GVHD >/= grade 2 between the matched and mismatched groups (P =.849). For patients in CR-2, the risk of relapse post-BMT was significantly lower if leukemic relapse occurred off-treatment (P =.005). The Kaplan-Meier overall and leukemia-free survival (LFS) estimates for recipients of matched and mismatched BMT, respectively, at 36 months were 49% versus 42% (P =.380) and 45% versus 40% (P =.654). Although HLA mismatching results in an increased occurrence of primary graft failure with T-cell-depleted allografts, it allows more donors to be identified rapidly for children with ALL without compromising overall transplant outcome.
authors.affiliation: National Blood Service, Bristol, UK.
authors.forename: A
authors.initials: A
authors.lastname: Green
authors.forename: E
authors.initials: E
authors.lastname: Clarke
authors.forename: L
authors.initials: L
authors.lastname: Hunt
authors.forename: A
authors.initials: A
authors.lastname: Canterbury
authors.forename: A
authors.initials: A
authors.lastname: Lankester
authors.forename: G
authors.initials: G
authors.lastname: Hale
authors.forename: H
authors.initials: H
authors.lastname: Waldmann
authors.forename: S
authors.initials: S
authors.lastname: Goodman
authors.forename: J M
authors.initials: JM
authors.lastname: Cornish
authors.forename: D I
authors.initials: DI
authors.lastname: Marks
authors.forename: C G
authors.initials: CG
authors.lastname: Steward
authors.forename: A
authors.initials: A
authors.lastname: Oakhill
authors.forename: D H
authors.initials: DH
authors.lastname: Pamphilon
mesh_terms: D000293:Adolescent; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D016026:Bone Marrow Transplantation / Q000276:immunology / Q000401:mortality; D002648:Child; D002675:Child, Preschool; D016572:Cyclosporine / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D015236:HLA-C Antigens / Q000276:immunology; D006650:Histocompatibility Testing; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007223:Infant; D019520:Living Donors / Q000145:classification; D008212:Lymphocyte Depletion / Q000379:methods; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D012737:Sex Factors; D016019:Survival Analysis; D013601:T-Lymphocytes; D013997:Time Factors; D014184:Transplantation, Homologous; D017211:Treatment Failure; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D015236:HLA-C Antigens; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D008727:Methotrexate