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Children with acute lymphoblastic leukemia who receive T-cell-depleted MLA mismatched marrow allografts from unrelated donors have an increased incidence of primary graft failure but a similar overall transplant outcome
Author(s): Green A, Clarke E, Hunt L, Canterbury A, Lankester A, Hale G, Wadmann H, Goodman S, Cornish JM, Marks DI, Steward CG, Oakhill A, Pamphilon DH
Source: BLOOD    Volume: 94    Issue: 7    Pages: 2236-2246    Published: OCT 1 1999  
Times Cited: 54     References: 43     
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 greater than or equal to 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. (C) 1999 by The American Society of Hematology.
Document Type: Article
Language: English
Reprint Address: Pamphilon, DH (reprint author), Royal Hosp Sick Children, St Michaels Hill, Bristol BS2 8BJ, Avon England
Addresses:
1. Royal Hosp Sick Children, Bristol BS2 8BJ, Avon England
2. Natl Blood Serv, Bristol, Avon England
3. Inst Transfus Sci, Bristol, Avon England
4. Univ Bristol, Div Child Hlth, Bristol, Avon England
5. Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 3RE, England
Publisher: AMER SOC HEMATOLOGY, 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA
Subject Category: Hematology
IDS Number: 242HT
ISSN: 0006-4971
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