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Induction of in vitro graft-versus-leukemia activity following bone marrow
transplantation for chronic myeloid leukemia
S Mackinnon, JM Hows and JM Goldman
MRC/LRF Leukaemia Unit, Royal Postgraduate Medical School, London, England.
We studied the in vitro effects of lymphokine-activated killer (LAK) cells
from the peripheral blood of chronic myeloid leukemia (CML) patients after
allogeneic and syngeneic bone marrow transplantation (BMT). LAK cells were
generated by incubating peripheral blood mononuclear cells from patients
post-BMT with recombinant interleukin-2 (IL-2) (500 U/mL) in 10% AB serum
for 7 days. They were phenotyped and tested for activity in a standard
4-hour 51Cr release assay (n = 37) and in a CFU-GM assay (n = 24). We found
that the LAK cells were mainly activated natural killer cells, but some
were CD3+ T cells. In the 51Cr release assay LAK cells from 20 of 33 (61%)
allogeneic and 2 of 4 syngeneic recipients killed recipient CML cells and
in 22 of 37 (60%) cases also killed the HLA disparate CML cells. In the
CFU-GM assay the LAK cells incubated together with the CML cells in liquid
culture before plating inhibited (P less than .05) colony growth in 16 of
22 allogeneic and 2 of 2 syngeneic recipients. Cell-cell contact was
necessary for optimal effect. There was little or no inhibition of
proliferation of donor marrow CFU-GM. This in vitro graft-versus- leukemia
(GVL) effect could also be demonstrated after LAK effectors were depleted
of CD3+ T cells. It was inducible in recipients of both T cell-depleted and
T cell-replete donor marrow and in recipients with or without
graft-versus-host disease. These results suggest that a major
histocompatibility complex-unrestricted GVL effect is inducible following
allogeneic and syngeneic BMT. The use of IL-2/LAK cells after BMT could
reduce the risk of relapse.
Volume 76,
Issue 10,
pp. 2037-2045,
11/15/1990
Copyright © 1990 by The American Society of Hematology
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