INTERLEUKIN-1-ALPHA ADMINISTERED AFTER AUTOLOGOUS TRANSPLANTATION - APHASE I II CLINICAL-TRIAL/

Interleukin-1 alpha (IL-1 alpha) can act as both a hematopoietic growt h factor and a stimulant of cellular and humoral immune responses. To promote acceleration of hematologic recovery and induce immune antitum or activity, we initiated a phase I/II dose escalation trial of 6-hour daily infusions of recombinant human IL-1 alpha after autologous tran splantation. Forty patients with Hodgkin's disease (n = 9) and non-Hod gkin's lymphoma (n = 31) transplanted with unmobilized autologous peri pheral blood stem cells or bone marrow stem cells received daily B-hou r infusions of IL-1 alpha (day 0 to day +13) at daily doses between 0. 1 to 10 mu g/m(2)/d; 7 patients received only 7 planned days of IL-1 a lpha (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-rela ted fever (occurring on a median of 9 of 14 treatment days), fatigue, and severe chills. Hypotension was dose-limiting and led to discontinu ation of IL-1 alpha in both patients receiving 10 mu g/ m(2)/d. IL-1 a lpha-treated patients receiving 3.0 mu g/m(2)/d (the maximum tolerated dose) achieved neutrophil recovery (absolute neutrophil count greater than 500/mu L) significantly earlier (median, 12 days; range, 11 to 2 7) than untreated control patients or those receiving IL-1 alpha at 0. 1 to 1.0 mu g/ m(2)/d (median, 27; range, 9 to 63; P <.0001). In addit ion, the IL-1 alpha patients' bone marrows at day +14 were significant ly enriched with committed myeloid progenitor cells. Strong trends to earlier freedom from red blood cell (P =.06) and platelet (P =.09) tra nsfusions were also noted after IL-1 alpha treatment. This earlier hem atopoietic engraftment after 3.0 mu g/m(2)/d IL-1 alpha allowed earlie r 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 accel erated hematopoiesis and immune response activation observed in this t rial suggest the value of its further investigation in controlled tria ls and perhaps in combination with other hemopoietins after transplant ation. (C) 1994 by The American Society of Hematology.