S. O'Brien et al., Sequential homoharringtonine and interferon-alpha in the treatment of early chronic phase chronic myelogenous leukemia, BLOOD, 93(12), 1999, pp. 4149-4153
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.