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Toxicity and immunomodulatory effects of interleukin-2 after autologous
bone marrow transplantation for hematologic malignancies
CM Higuchi, JA Thompson, FB Petersen, CD Buckner and A Fefer
Department of Medicine, University of Washington, Seattle 98195.
Autologous bone marrow transplantation (ABMT) for advanced hematologic
malignancies is associated with high relapse rates. Interleukin-2 (IL- 2)
and lymphokine-activated killer (LAK) cells represent a potentially
non-cross-resistant therapeutic modality that might prevent or delay
relapses if used early after ABMT at a time when the tumor burden is
minimal. However, high-dose chemoradiotherapy and ABMT might increase
patients' susceptibility to IL-2 toxicity, and might interfere with
immunologic responses to IL-2 in vivo. Therefore, to determine safety,
tolerance, and immunomodulatory effects of IL-2 therapy early after ABMT,
IL-2 was administered by continuous intravenous infusion to 16 patients 14
to 91 days (median, 33) after ABMT for acute leukemia, lymphoma, or
multiple myeloma. Patients were sequentially assigned to escalating IL-2
"induction" doses (0.3 to 4.5 x 10(6) U/m2/d, days 1 to 5), and all
patients received a nonescalating IL-2 "maintenance" dose (0.3 x 10(6)
U/m2/d, days 12 to 21). Most patients exhibited mild to moderate fever,
nausea, diarrhea, and/or skin rash with IL-2 infusions. The maximum
tolerated "induction" dose was 3.0 x 10(6) U/m2/d; dose- limiting
toxicities were hypotension and thrombocytopenia. All toxicities reversed
on stopping the IL-2 infusions, and all patients completed "maintenance."
Postinfusion lymphocytosis was exhibited by patients at all IL-2 dose
levels. With the higher IL-2 doses, increased percentages of patients' PBMC
expressed CD16 and CD56, with augmented lysis of K562 and Daudi, reflecting
the induction of natural killer and circulating LAK effector activities.
Increased LAK precursor activity was exhibited by patients at all IL-2 dose
levels. Thus, the IL-2 therapy regimen was safely tolerated after ABMT, and
pronounced immunomodulatory effects were observed with the higher IL-2
doses. These studies support the planned use of IL-2 and LAK cells after
ABMT in an attempt to reduce relapses of advanced hematologic malignancies.
Volume 77,
Issue 12,
pp. 2561-2568,
06/15/1991
Copyright © 1991 by The American Society of Hematology
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