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Bone marrow transplantation for chronic myeloid leukemia with volunteer
unrelated donors using ex vivo or in vivo T-cell depletion: major
prognostic impact of HLA class I identity between donor and recipient
A Spencer, RM Szydlo, PA Brookes, E Kaminski, S Rule, F van Rhee, KN Ward, G Hale, H Waldmann and JM Hows
Leukaemia Research Fund Centre for Adult Leukaemia, Royal Postgraduate
Medical School, London, UK.
Between August 1985 and July 1994, we performed 115 volunteer unrelated
donor (VUD) bone marrow transplants (BMT) for first chronic phase (n = 86)
or advanced phase (n = 29) chronic myeloid leukemia (CML). Standard
serologic HLA typing of potential donors and recipients was supplemented
with one-dimensional isoelectric focusing (IEF) for class I proteins,
allogenotyping for DR and DQ alleles using DNA restriction fragment length
polymorphism (RFLP) analysis, and the measurement of antirecipient major
histocompatibility complex (MHC) cytotoxic T- lymphocyte precursor cells in
the donors' blood (CTLp assay). Recipients were conditioned for
transplantation with a combination of high-dose chemotherapy and total body
irradiation (n = 103) or high- dose chemotherapy alone (n = 12). Twenty
eight recipients received ex vivo T-cell-depleted marrow, and 84 underwent
some form of in vivo T- cell depletion. The probability of severe (grades
III or IV) acute graft-versus-host disease (aGVHD) was 24%, and that of
extensive chronic graft-versus-host disease (cGVHD), 38%. Proportional
hazards regression analysis showed an association between low frequency
CTLp and a reduced incidence of severe aGVHD (relative risk [RR], 0.28; P =
.0035). The probability of relapse at 3 years was 23%, with first chronic
phase disease being independently associated with a lower risk of relapse
(RR, 0.71; P = .01). The overall leukemia-free survival (LFS) at 3 years
was 37%; the LFS for the first chronic phase and advanced phase recipients
was 41% and 26%, respectively. First chronic phase disease (RR, 0.56; P =
.063) and the combination of recipient cytomegalovirus (CMV) seronegativity
and an IEF-matched donor (RR, 0.48; P = .011) were both associated with
improved LFS. The probabilities of survival and LFS for patients under 40
years of age transplanted in first chronic phase from an IEF-matched donor
were 73% and 50%, respectively. We conclude that VUD BMT is a reasonable
option for patients with CML; when using ex vivo or in vivo T-cell
depletion, optimal results are achieved in patients transplanted in chronic
phase with marrow from donors without demonstrable class I HLA mismatch and
a low CTLp frequency.
Volume 86,
Issue 9,
pp. 3590-3597,
11/01/1995
Copyright © 1995 by The American Society of Hematology
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