Journal of Clinical Oncology, Vol 16, 3279-3285, Copyright © 1998 by American Society of Clinical Oncology
Suppression of cytogenetic clonal evolution with interferon alfa therapy in patients with Philadelphia chromosome-positive chronic myelogenous leukemia
J Cortes, M Talpaz, S O'Brien, MB Rios, A Majlis, M Keating, EJ Freireich and H Kantarjian
Department of Leukemia, The University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
PURPOSE: To investigate whether cytogenetic clonal evolution can be
suppressed with interferon alfa (IFN-alpha) therapy in patients with
chronic myelogenous leukemia (CML). PATIENTS AND METHODS: Ninety patients
with CML and cytogenetic clonal evolution who received IFN- alpha-based
regimens were analyzed. Clonal evolution was defined as the presence of
karyotypic abnormalities in addition to the Philadelphia (Ph) chromosome.
Patients were evaluated for the suppression of cytogenetic clonal evolution
after therapy, the cytogenetic response, and survival. RESULTS: The median
age of the population was 39 years (range, 15 to 70 years), median time
from diagnosis to clonal evolution 14 months (range, 0 to 145 months), and
median percentage of abnormal metaphases 18% (range, 4% to 100%). Fifty six
patients (62%) achieved some suppression of cytogenetic clonal evolution;
in 41 patients (46%), the suppression was complete. The overall median
survival was 51 months, with 43% alive at 5 years. Patients who achieved a
complete suppression of cytogenetic clonal evolution had a median survival
of 66 months, with 51% alive at 5 years. Characteristics associated with a
better response include a lower percentage of abnormal metaphases, time to
cytogenetic clonal evolution of 24 months or less, and absence of other
features of accelerated disease. A prognostic classification for
cytogenetic clonal evolution defined three groups with complete response
(CR) rates of 85%, 34%, and 0% (P < .0001) and median survival times of
58, 31, and 30 months, respectively (P=.02). CONCLUSION: Patients with
cytogenetic clonal evolution can respond to IFN-alpha therapy, and this
response is associated with longer survival. A previously described
prognostic model separates patients into subsets with different
probabilities of response to IFN-alpha and survival.
