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Blood, Vol. 94 No. 7 (October 1), 1999:
pp. 2236-2246
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
Ann Green,
Emer Clarke,
Linda Hunt,
Andrew Canterbury,
Alan Lankester,
Geoff Hale,
Herman Waldmann,
Sally Goodman,
Jacqueline
M. Cornish,
David I. Marks,
Colin G. Steward,
Anthony Oakhill, and
Derwood H. Pamphilon
From the National Blood Service and Institute for Transfusion
Sciences, Bristol; the Division of Child Health, University of Bristol,
Bristol, UK; Sir William Dunn School of Pathology, University of
Oxford, Oxford, UK; and the Royal Hospital for Sick Children,
Bristol, UK.
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.
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