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Comparison Between Patients With Philadelphia-Positive Chronic Phase Chronic Myeloid Leukemia Who Obtained a Complete Cytogenetic Response Within 1 Year of Imatinib Therapy and Those Who Achieved Such a Response After 12 Months of Treatment

From the Institute of Hematology and Medical Oncology "Seràgnoli", University of Bologna, Bologna; Division of Hematology and Internal Medicine, Department of Clinical and Biological Science, University of Turin, Turin; Division of Hematology, University "Tor Vergata", and Division of Hematology, University "La Sapienza", Rome; Division of Hematology, Hospital "Pugliese Ciaccio", Catanzaro; Division of Hematology, University of Brescia; Division of Hematology and Internal Medicine, University of Genova; Division of Hematology, Hospital "Bianchi Malacrino Morelli", Reggio Calabria; CEINGE Biotecnologie Avanzate and Department of Biochemistry and Medical Biotechnology, University of Naples Federico II, Naples, Italy

Address reprint requests to Giovanni Martinelli, MD, Molecular Biology Unit, Institute of Hematology and Medical Oncology "Seràgnoli", University of Bologna, Via Massarenti, 9-40138 Bologna, Italy; e-mail: gmartino{at}kaiser.alma.unibo.it

Purpose Imatinib mesylate is a potent inhibitor of BCR-ABL, the constitutively active tyrosine kinase protein critical for the pathogenesis of chronic myeloid leukemia.

Patients and Methods We reviewed 284 patients with late chronic-phase Philadelphia chromosome (Ph) –positive chronic myeloid leukemia treated with imatinib 400 mg daily after interferon- failure. In a retrospective study, we evaluated the pattern and rapidity of the response to imatinib, comparing the cytogenetic and molecular responses, progression-free and overall survival rates in patients who obtained a complete cytogenetic response within 1 year of treatment (early responders), and in patients where a complete cytogenetic response was detected after 12 months (late responders).

Results After 3 or 4 years of treatment, the molecular response of the late cytogenetic responders was similar to that of the early cytogenetic responders. At 36 months of treatment the amount of residual disease measured by standardized quantitative reverse-transcriptase polymerase chain reaction was 0.00047 in late responders versus 0.00022 in early responders, and at 48 months it was 0.00019 versus 0.00026 (median values, P value = nonsignificant). The estimated 4-year progression-free survival rate was 88% for early responders and 100% for late responders, while the estimated 4-year overall survival rates were 92% and 100% for early and late responders, respectively.

Conclusion The sensitivity and the response (cytogenic and molecular) to imatinib may require 1 year or more. Long-term follow-up results continue to improve in terms of rates and durability of the complete cytogenetic response, major or complete molecular response, and progession-free and overall survival.

Supported by COFIN 2003 (Molecular therapy of Ph-positive leukemias), by FIRB 2001, by the University of Bologna (grants 60%), by the Italian Association for Cancer Research (A.I.R.C.), by Fondazione del Monte di Bologna e Ravenna, by European LeukemiaNet founds, and by Associazione Italiana contro le Leucemie grants.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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