Effects of recombinant interleukin-2 administration on cytotoxic function
following high-dose chemo-radiotherapy for hematological malignancy
DJ Gottlieb, HG Prentice, HE Heslop, C Bello-Fernandez, AC Bianchi, AR Galazka and MK Brenner
Department of Haematology, Royal Free Hospital, London, England.
Activated killer cells, unrestricted by major histocompatibility (MHC)
antigens circulate in the peripheral blood of patients who have undergone
autologous and allogeneic bone marrow transplant (BMT) and may contribute
to the reduced risk of leukemic relapse observed after these procedures.
Interleukin-2 (IL-2) in vitro augments this cytotoxicity and used
therapeutically might thereby promote the eradication of minimal residual
disease. In order to assess whether these effects on cytotoxicity can be
reproduced in vivo, we studied changes in number, phenotype, and MHC
unrestricted cytotoxicity of peripheral blood mononuclear cells obtained
from patients with hematologic malignancy receiving IL-2 infusions.
Patients with acute myeloid leukemia and multiple myeloma were treated
after cytotoxic chemotherapy or autologous BMT. IL-2 infusions produced an
initial lymphopenia, followed by a progressive recovery in mononuclear cell
numbers and a rebound lymphocytosis after the termination of treatment.
This affected all lymphocyte subsets; in particular CD25 (IL-2 receptor)
positive cell numbers rose sevenfold. Cells with the ability to kill a
natural killer (NK)-resistant, lymphokine activated killer cell
(LAK)-sensitive target appeared in the circulation during 16 of 19
infusions and mean LAK activity rose from 5.9% to 15.5% during infusion
(E:T ratio, 50:1; P less than .001). During IL-2 infusion, cells present in
the peripheral blood inhibited the growth of myeloid leukemia blasts in
agar after overnight co-culture. Depletion experiments showed that LAK
activity was mediated by cells of both CD3- CD16+ (NK derived) and CD3+
CD16- (T derived) subsets. LAK precursor activity in peripheral blood also
significantly increased during IL-2 infusion. Increases in major
histocompatibility complex (MHC) unrestricted cytotoxicity can be produced
by IL-2 infusions in vivo and may result in improved relapse-free survival
following chemotherapy or BMT.
Volume 74,
Issue 7,
pp. 2335-2342,
11/15/1989
Copyright © 1989 by The American Society of Hematology
