Sequential homoharringtonine and interferon-alpha in the treatment of early chronic phase chronic myelogenous leukemia

Homoharringtonine (HHT) is a novel plant alkaloid that produced a complete hematologic remission (CHR) in 72% of patients with late chronic phase chro nic myelogenous leukemia (CML). Cytogenetic (CG) remissions were noted in 3 1%. In this study, six courses of HHT were administered to 90 patients with early chronic phase CML (< 1 year from diagnosis). Patients then received interferon-alpha (IFN-alpha) with a target dose of 5 MU/m(2) daily. Results were compared with those in a prior group of patients treated with IFN-alp ha-based therapy between 1982 and 1990, Ninety-two percent of patients achi eved CHR with HHT; CG responses were observed in 60% and were major in 27%. Both CHR and CG response rates were significantly higher than those seen i n historical control patients after 6 months of IFN-alpha therapy. After re ceiving HHT, patients required lower doses of IFN-alpha to maintain a CHR. The median dose delivered was 2.4 MU/m(2). This reduction in IFN-alpha dose was associated with a lower incidence of myalgia and gastrointestinal (GI) disturbances than that seen in patients treated at the 5 MU/m2 dose. Overa ll, CG responses were seen in 66% of the patients who received HHT and IFN- alpha compared with 61% of the historical control patients. HHT is a very e ffective treatment of early chronic phase CML, and ongoing trials are inves tigating the simultaneous administration of HHT and IFN-alpha, as well as t hat of HHT and low-dose cytosine arabinoside in patients failing IFN-alpha therapy. (C) 1999 by The American Society of Hematology.