Children with acute lymphoblastic leukemia who receive T-cell-depleted MLAmismatched marrow allografts from unrelated donors have an increased incidence of primary graft failure but a similar overall transplant outcome
A. Green et al., Children with acute lymphoblastic leukemia who receive T-cell-depleted MLAmismatched marrow allografts from unrelated donors have an increased incidence of primary graft failure but a similar overall transplant outcome, BLOOD, 94(7), 1999, pp. 2236-2246
Disparity for HLA in unrelated donor bone marrow transplantation (BMT) incr
eases 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-ce
ll depletion and cyclosporin A was given to 134 children together with shor
t-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 HL
A-DR and -DQ loci. Overall graft failure was increased in recipients of mar
row mismatched at either HLA-A, -B, -DR, or -DQ (15.7% v 4.8%; P = .057) ma
inly because there was a higher proportion of children with primary graft f
ailure (11.8% v 1.2%; P = .012). The presence of an HLA-C locus mismatch di
d 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 patie
nts in CR-2, the risk of relapse post-BMT was significantly lower if leukem
ic relapse occurred off-treatment (P = .005). The Kaplan-Meier overall and
leukemia-free survival (LFS) estimates for recipients of matched and mismat
ched BMT, respectively, at 36 months were 49% versus 42% (P = .380) and 45%
versus 40% (P = .654). Although HLA mismatching results in an increased oc
currence of primary graft failure with T-cell-depleted allografts, it allow
s more donors to be identified rapidly for children with ALL without compro
mising overall transplant outcome. (C) 1999 by The American Society of Hema
tology.