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Interleukin-1 alpha administered after autologous transplantation: a phase
I/II clinical trial
D Weisdorf, E Katsanis, C Verfaillie, NK Ramsay, R Haake, L Garrison and BR Blazar
Department of Medicine, University of Minnesota, Minneapolis.
Interleukin-1 alpha (IL-1 alpha) 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-1 alpha 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-1 alpha (day
0 to day +13) at daily doses between 0.1 to 10 micrograms/m2/d; 7 patients
received only 7 planned days of IL-1 alpha (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-1 alpha- 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-1 alpha in both patients receiving 10
micrograms/m2/d. IL-1 alpha-treated patients receiving 3.0 micrograms/m2/d
(the maximum tolerated dose) achieved neutrophil recovery (absolute
neutrophil count greater than 500/microL) significantly earlier (median, 12
days; range, 11 to 27) than untreated control patients or those receiving
IL-1 alpha at 0.1 to 1.0 micrograms/m2/d (median, 27; range, 9 to 63; P
< .0001). In addition, the IL-1 alpha 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-1 alpha treatment. This earlier
hematopoietic engraftment after 3.0 micrograms/m2/d IL-1 alpha allowed
earlier hospital discharge (median, 25 v 37 days for control or low- dose
IL-1 alpha patients [P < .0001]) and a concomitant reduction (by
$38,000) in median hospital charges (P = .01). The clinical toxicities of
IL-1 alpha 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.
Volume 84,
Issue 6,
pp. 2044-2049,
09/15/1994
Copyright © 1994 by The American Society of Hematology
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