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Anti-leukemia potential of interleukin-2 activated natural killer cells
after bone marrow transplantation for chronic myelogenous leukemia
M Hauch, MV Gazzola, T Small, C Bordignon, L Barnett, I Cunningham, H Castro- Malaspinia, RJ O'Reilly and CA Keever
Bone Marrow Transplantation Service, Memorial Sloan-Kettering Cancer
Center, New York, NY.
The anti-leukemia potential of natural killer (NK) cells has been evaluated
in 40 patients transplanted for chronic myelogenous leukemia (CML) to
determine whether differences in NK cell function were correlated with
subsequent leukemic relapse. Cells from patients and their donors were
tested in 51Cr release assays against fully allogeneic CML targets and
against cultured K562 targets; cells from 26 patients were tested against
host-derived CML targets that were cryopreserved before transplantation.
Cultured CML targets (K562) were highly susceptible to lysis by freshly
isolated peripheral blood lymphocytes (PBL) and to a greater degree by PBL
cultured in medium containing interleukin-2 (IL-2) in all assays performed.
In contrast, noncultured CML targets were lysed only by IL-2-activated
cells from a subset of patients. When present, lytic activity to CML
targets was detectable as early as 3 weeks after bone marrow
transplantation, and remained positive throughout the posttransplant
period. Optimal lytic activity developed within the first week of culture
and required greater than or equal to 250 U/mL of IL-2 in the culture
medium. Lytic activity to fully allogeneic and host-derived CML targets
appeared to be mediated by CD16+ and CD56+ cells but not by CD3+ cells.
Lysis of allogeneic CML targets was variable, but patients could be divided
into two groups: those with and those without lytic activity to the
majority of targets tested. The basis for the differences in lytic activity
could not be ascribed to target susceptibility to lysis, the proportion of
NK cells in the cultures, or to the phenotype of the NK cell subsets in the
cultures. When tested in parallel, the lytic activity of donor and
recipient cultures against host-derived CML targets was highly correlated,
suggesting that there may be inherent differences in the ability of NK
cells to recognize CML targets. The risk of relapse for patients who failed
to generate lytic activity against host-derived CML targets was
significantly increased over that for patients with lytic activity against
host leukemia. These data indicate that posttransplant immunotherapy with
IL-2 designed to activate NK cells will likely augment the
graft-versus-leukemia potential of the graft.
Volume 75,
Issue 11,
pp. 2250-2262,
06/01/1990
Copyright © 1990 by The American Society of Hematology
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