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Clinical and immunologic effects of prolonged infusion of low-dose
recombinant interleukin-2 after autologous and T-cell-depleted allogeneic
bone marrow transplantation
RJ Soiffer, C Murray, K Cochran, C Cameron, E Wang, PW Schow, JF Daley and J Ritz
Division of Tumor Immunology, Dana-Farber Cancer Institute, Boston, MA
02115.
Bone marrow transplantation (BMT) can produce prolonged clinical remission
in some patients with hematologic malignancies. Unfortunately, disease
relapse may occur despite BMT. Studies in animal models and clinical
experience have provided evidence that immunologic factors play an
important role in preventing relapse post-BMT. To stimulate immunologic
activity in patients post-BMT, we administered prolonged uninterrupted
continuous infusions of low-dose recombinant interleukin-2 (rIL-2).
Thirteen marrow recipients (seven autologous BMT, six CD6 T-depleted
allogeneic BMT) received rIL-2 at a dose of 2 x 10(5) U/m2/d for a
scheduled period of 90 days. rIL-2 was administered through a Hickman
catheter with a portable pump beginning a median of 85 days after BMT.
Toxicity was minimal and all treatment could be undertaken in the
outpatient setting. No patient developed any signs of graft-versus-host
disease, hypotension, or pulmonary capillary leak syndrome. Treatment did
not affect the absolute neutrophil count or hemoglobin level, but
eosinophils increased substantially in most patients. Platelet counts
decreased by 20% in 10 of 13 individuals within 2 weeks, but stabilized
thereafter. Despite the low dose of rIL- 2 administered, significant
immunologic changes were noted. Specifically, all 13 patients experienced a
marked increase (fivefold to 40-fold) in natural killer (NK) cell number.
Phenotypic characterization showed that the majority of NK cells were
CD56bright+ CD16+ CD3-. In contrast, a minor increase in T-cell number was
noted in only 4 of 13 patients. Low-dose rIL-2 treatment resulted in
augmentation of in vitro cytotoxicity against K562 and COLO tumor targets.
This cytotoxic activity could be dramatically enhanced by incubation with
additional rIL-2 in vitro. The immunologic effects of rIL-2 treatment were
similar in both autologous and allogeneic marrow recipients. Our data
suggest that prolonged infusion of rIL-2 at low doses is safe and can
selectively increase NK cell number and activity after BMT. Further studies
to assess the impact these changes may have on disease relapse post-BMT
will be undertaken.
Volume 79,
Issue 2,
pp. 517-526,
01/15/1992
Copyright © 1992 by The American Society of Hematology
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