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Achieving a Major Molecular Response at the Time of a Complete Cytogenetic Response (CCgR) Predicts a Better Duration of CCgR in Imatinib-Treated Chronic Myeloid Leukemia Patients

Authors' Affiliations: ¹ Institute of Hematology and Medical Oncology "Seràgnoli," University of Bologna, Bologna, Italy; ² Division of Hematology and Internal Medicine, Department of Clinical and Biological Science, University of Turin, Turin, Italy; ³ CEINGE Biotecnologie Avanzate and Department of Biochemistry and Medical Biotechnology, University of Naples Federico II, Naples, Italy; ⁴ Division of Hematology, Ospedali Riuniti, Bergamo, Italy; ⁵ Department of Cellular Biotechnology and Hematology, University "La Sapienza," Rome, Italy; ⁶ Department of Hematology, University of Siena, Siena, Italy; ⁷ Division of Hematology, Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, University of Pavia, Pavia, Italy; and ⁸ Department of Hematology, San Martino Hospital, Genova, Italy

Requests for reprints: Giovanni Martinelli, Molecular Biology Unit, Institute of Hematology and Medical Oncology "Seràgnoli," University of Bologna, Via Massarenti, 9, 40138 Bologna, Italy. Phone: 39-051-6363829; Fax: 39-051-6364037; E-mail: gmartino{at}kaiser.alma.unibo.it.

Purpose: Most patients with chronic-phase chronic myeloid leukemia (CML) who receive imatinib achieve a complete cytogenetic remission (CCgR) and low levels of BCR-ABL transcripts. CCgR is durable in the majority of patients but relapse occurs in a subset.

Experimental Design: To determine the potential of quantitative reverse transcription-PCR of BCR-ABL to predict cytogenetic relapse, we serially monitored residual disease in 97 CML patients with an imatinib-induced CCgR. Patients with late chronic phase CML after IFN- failure were treated with imatinib (400 mg daily).

Results: During the imatinib median follow-up time of 36 months (range, 12-54 months), disease monitoring occurred by cytogenetics and quantitative PCR. Twenty percent of patients experienced cytogenetic relapse at a median of 18 months after CCgR and a median of 24 months after starting imatinib. None of the possible prognostic factors studied in univariate and multivariate analyses seemed to predict for loss of cytogenetic response but the reduction of BCR-ABL transcript levels at the time of CCgR is an important prognostic factor.

Conclusions: In our study, we showed not only that achieving a major molecular remission at 12 months is predictive of a durable cytogenetic remission but also that patients who achieved a major molecular remission (expressed both as the BCR-ABL/ß2 microglobulin ratio % <0.0005 and as a 3-log reduction from median baseline value) already at the time of first achieving a CCgR have significantly longer cytogenetic remission durations than those without this magnitude of molecular response (P < 0.05).

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