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Blood, Vol. 93 No. 12 (June 15), 1999:
pp. 4149-4153
Sequential Homoharringtonine and Interferon- in the Treatment of
Early Chronic Phase Chronic Myelogenous Leukemia
Susan O'Brien,
Hagop Kantarjian,
Charles Koller,
Eric Feldman,
Miloslav Beran,
Michael Andreeff,
Sergio Giralt,
Bruce Cheson,
Michael Keating,
Emil Freireich,
Mary Beth Rios, and
Moshe Talpaz
From the Departments of Leukemia, Bioimmunotherapy, and Blood and
Marrow Transplant, Division of Medicine, The University of Texas M.D.
Anderson Cancer Center, Houston, TX; and the National Cancer Institute,
Bethesda, MD.
Homoharringtonine (HHT) is a novel plant alkaloid that produced a
complete hematologic remission (CHR) in 72% of patients with late
chronic phase chronic myelogenous leukemia (CML). Cytogenetic (CG)
remissions were noted in 31%. 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- (IFN-) with a
target dose of 5 MU/m2 daily. Results were compared with
those in a prior group of patients treated with IFN--based therapy
between 1982 and 1990. Ninety-two percent of patients achieved 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 in
historical control patients after 6 months of IFN- therapy. After
receiving HHT, patients required lower doses of IFN- to maintain a
CHR. The median dose delivered was 2.4 MU/m2. This
reduction in IFN- 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. Overall, CG responses
were seen in 66% of the patients who received HHT and IFN- compared
with 61% of the historical control patients. HHT is a very effective
treatment of early chronic phase CML, and ongoing trials are
investigating the simultaneous administration of HHT and IFN-, as
well as that of HHT and low-dose cytosine arabinoside in patients
failing IFN- therapy.
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