Interleukin 2 immediately after autologous bone marrow transplantation for acute lymphoblastic leukemia a phase I study

Daniel J. Weisdorf, Peter M. Anderson, Bruce R. Blazar, Fatih M. Uckun, John H. Kersey, Norma K.C. Ramsay

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59 Scopus citations

Abstract

Despite intensive conditioning and marrow purging, leukemia relapse frequently follows autologous BMT for acute lymphoblastic leukemia. To generate antileukemic immunologic activity, we performed a phase I study using recombinant human interleukin 2 given immediately posttransplantation. This early period was chosen because of low disease burden; therefore induced in vivo effectorrtarget cell ratios might be most favorable. IL-2 was given by continuous infusion (96 hr/week X 3 weeks) beginning day +1. Fourteen patients with high-risk ALL were treated at 0.5, 1.0, and 2.0 X 106 U/m2/ day IL-2. The clinical toxicity, hemopoietic recovery, and immune activation in the IL-2-treated patients was compared with that in a group of autologous BMT patients receiving no IL-2. The patients receiving IL-2 had a trend toward earlier neutrophil, platelet, and RBC recovery plus earlier hospital discharge versus non—IL-2 controls. However, IL-2 plus the inherent toxicity of transplantation often produced hepatic, pulmonary, and renal toxicity. Assessment of immune activation induced by in vivo IL-2 (following 3 weeks of IL-2) showed proliferation of CD8+ T cells having in vitro cytotoxicity against the Nalm-6 ALL cell line in most patients. Little enhancement of natural killer activity by immunophenotype or cytotoxicity against K562 cells was observed. IL-2 given immediately post-BMT induces infrequent but significant toxicity at lower doses than in the non-BMT setting. This toxicity may result from pre-BMT conditioning in conjunction with T cell activation. The immunotherapeutic potential, dose, and schedule of IL-2 following BMT require further study along with measures to reduce its toxicity.

Original languageEnglish (US)
Pages (from-to)61-66
Number of pages6
JournalTransplantation
Volume55
Issue number1
DOIs
StatePublished - Jan 1993

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