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 et al., 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, Blood, 86(9), 1995, pp. 3590-3597
Between August 1985 and July 1994, we performed 115 volunteer unrelate
d donor (VUD) bone marrow transplants (BMT) for first chronic phase (n
= 86) or advanced phase (n = 29) chronic myeloid leukemia (CML). Stan
dard serologic HLA typing of potential donors and recipients was suppl
emented with one-dimensional isoelectric focusing (IEF) for class I pr
oteins, allogenotyping for DR and DO alleles using DNA restriction fra
gment length polymorphism (RFLP) analysis, and the measurement of anti
recipient major histocompatibility complex (MHC) cytotoxic T-lymphocyt
e precursor cells in the donors' blood (CTLp assay), Recipients were c
onditioned for transplantation with a combination of high-dose chemoth
erapy and total body irradiation (n = 103) or high-dose chemotherapy a
lone (n = 12), Twenty eight recipients received ex vivo T-cell-deplete
d marrow, and 84 underwent some form of in vivo T-cell depletion. The
probability of severe (grades III or IV) acute graft-versus-host disea
se (aGVHD) was 24%, and that of extensive chronic graft-versus-host di
sease (cGVHD), 38%. Proportional hazards regression analysis showed an
association between low frequency CTLp and a reduced incidence of sev
ere aGVHD (relative risk [RR], 0.28; P = .0035). The probability of re
lapse at 3 years was 23%, with first chronic phase disease being indep
endently 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 f
or the first chronic phase and advanced phase recipients was 41% and 2
6%, 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 i
mproved LFS. The probabilities of survival and LFS for patients under
40 years of age transplanted in first chronic phase from an IEF-matche
d 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 transplant
ed in chronic phase with marrow from donors without demonstrable class
I HLA mismatch and a low CTLp frequency. (C) 1995 by The American Soc
iety of Hematology.