DIVERGENT IN-VIVO AND IN-VITRO ANTILEUKEMIC ACTIVITY OF RECOMBINANT INTERFERON-BETA IN PATIENTS WITH CHRONIC-PHASE CHRONIC MYELOGENOUS LEUKEMIA

It was the aim of this study to investigate the antileukemic activities of recombinant interferon beta (rIFN beta) in chronic-phase CML in vitro and in vivo. Nine patients in the early chronic-phase of CML were treated in a phase-II trial with escalating doses of rIFN beta. In parallel, antiproliferative and immunomodulatory activities of rIFN beta and rIFN alpha 2b were studied in vitro. rIFN beta exhibited a significantly higher antiproliferative activity on hematopoietic progenitor cells of CML patients in vitro than rIFN alpha 2b. In contrast, only very limited clinical antileukemic efficacy of rIFN beta was observed. None of the patients achieved a complete or partial hematologic response (0% response rate, 0-36% 95 C.I.). Primary resistance of CML patients to rIFN beta treatment was caused neither by antibody formation against the recombinant material nor by deficient IFN receptor targeting and/or signaling: Induction of serum levels of beta-2-microglobulin (beta-2-m) and neopterin after administration of rIFN beta was comparable to that seen after administration of rIFN alpha. However, rIFN beta treatment less effectively induced biosynthesis of interleukin-1 receptor antagonist protein (IL-1-Ra) than rIFN alpha 2b. Thus, we conclude that rIFN beta at doses up to 12 MU/day s.c. is ineffective for treatment of chronic-phase CML. Further investigations into divergent biologic responses to various type-I interferons might help to elucidate mechanisms crucial for IFN action in patients with CML.