Interleukin-1α administered after autologous transplantation: A phase I/II clinical trial

Daniel Weisdorf, Emmanuel Katsanis, Catherine Verfaillie, Norma K.C. Ramsay, Robert Haake, Leslie Garrison, Bruce R. Blazar

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41 Scopus citations

Abstract

Interleukin-1α (IL-1α) can act as both a hematopoietic growth factor and a stimulant of cellular and humoral immune responses. To promote acceleration of hematologic recovery and induce immune antitumor activity, we initiated a phase I/II dose escalation trial of 6-hour daily infusions of recombinant human IL-1α after autologous transplantation. Forty patients with Hodgkin's disease (n = 9) and non-Hodgkin's lymphoma (n = 31) transplanted with unmobilized autologous peripheral blood stem cells or bone marrow stem cells received daily 6-hour infusions of IL-1α (day 0 to day +13) at daily doses between 0.1 to 10 μg/m2/d; 7 patients received only 7 planned days of IL- 1α (day 0 through 6). Most patients received all 14 days of therapy, although 5 patients discontinued treatment early (after 1 to 6 doses) because of fever and severe chills. Toxicity included IL-1α-related fever (occurring on a median of 9 of 14 treatment days), fatigue, and severe chills. Hypotension was dose-limiting and led to discontinuation of IL-1α in both patients receiving 10 μg/m2/d. IL-1α-treated patients receiving 3.0 μg/m2/d (the maximum tolerated dose) achieved neutrophil recovery (absolute neutrophil count greater than 500/μL) significantly earlier (median, 12 days; range, 11 to 27) than untreated control patients or those receiving IL- 1α at 0.1 to 1.0 μg/m2/d (median, 27; range, 9 to 63; P < .0001). In addition, the IL-1α patients' bone marrows at day +14 were significantly enriched with committed myeloid progenitor cells. Strong trends to earlier freedom from red blood cell (P = .06) and platelet (P = .09) transfusions were also noted after IL-1α treatment. This earlier hematopoietic engraftment after 3.0 μg/m2/d IL-1α allowed earlier hospital discharge (median, 25 v 37 days for control or low-dose IL-1α patients [P < .0001]) and a concomitant reduction (by $38,000) in median hospital charges (P = .01). The clinical toxicities of IL-1α infusion are substantial, though not life-threatening. The accelerated hematopoiesis and immune response activation observed in this trial suggest the value of its further investigation in controlled trials and perhaps in combination with other hemopoietins after transplantation.

Original languageEnglish (US)
Pages (from-to)2044-2049
Number of pages6
JournalBlood
Volume84
Issue number6
DOIs
StatePublished - Sep 15 1994

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