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

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.