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Homoharringtonine and Low-Dose Cytarabine in the Management of Late Chronic-Phase Chronic Myelogenous Leukemia

From the Departments of Leukemia, Bioimmunotherapy,Biostatistics, and Blood and Bone Marrow Transplantation,M.D. Anderson Cancer Center, Houston, TX; and the National CancerInstitute, Bethesda, MD.

Address reprint requests to Hagop M. Kantarjian, MD,Department of Leukemia, Box 61, M.D. Anderson Cancer Center, 1515Holcombe Blvd, Houston, TX 77030; emailhkantarj{at}mdanderson.org

PURPOSE: : To evaluate the efficacy andtoxicity profiles of a combination regimen of homoharringtonine (HHT)and low-dose cytarabine (ara-C) in patients with Philadelphiachromosome (Ph)–positive chronic myelogenous leukemia (CML) whohad experienced treatment failure with interferon alfa (IFN)therapy.

PATIENTS AND METHODS: One hundred five patients were treated: 100 in chronicphase (15 with cytogenetic clonal evolution) and five in acceleratedphase. Their median age was 52 years; all had been treatedunsuccessfully with IFN; 94% were in late chronic phase; 43% hadbeen exposed to ara-C and 11% had been exposed to HHT. Patientsreceived HHT 2.5 mg/m² by continuousinfusion daily for 5 days and ara-C 15mg/m² daily in two subcutaneous injectionsfor 5 days every 4 weeks. The outcome of the 100 patients in chronicphase was compared with a previous study group of 73 patients treatedwith HHT alone.

RESULTS: Overall, the complete hematologic response (CHR) rate in chronic phasewas 72%; the cytogenetic response rate was 32% (major response, 15%;complete response, 5%). Toxicities were acceptable, mostly related tomoderate diarrhea (3%), headaches (3%), cardiovascular events (3%),and myelosuppression-associated complications (3% to 14%). With amedian follow-up period of 25 months, the estimated 4-year survivalrate was 55%. Response rates were identical with HHT plus ara-C versusHHT alone, but the survival was significantly longer with thecombination after accounting for differences in the study groups andby multivariate analysis.

CONCLUSION: The combination regimen of HHT and ara-C is effective andsafe in patients with CML who have experienced treatment failure withIFN and needs to be investigated together with IFN as partof front-line CML therapy. The addition of ara-C did not improve theresponse rates but may have improved survival, perhaps throughsuppression of clones related to diseasetransformation.

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