ABSTRACT
BACKGROUND: Monitoring minimal residual disease (MRD) by real-time quantitative polymerase chain reaction (RT-PCR) in chronic myeloid leukemia (CML) patients is mandatory in the era of tyrosine kinase inhibitors. Achieving a major molecular response (MMR) at 12 and 18 months predicts a better progression and event-free survival. PATIENTS AND METHODS: The objective of this prospective, multicentric study was to evaluate MRD by standardized RT-PCR in 178 patients with chronic-phase CML who were treated with imatinib at different institutions in Argentina and Uruguay and to determine if achievement of a stable MMR (BCR-ABL transcript levels < 0.1%) identifies a low-risk cytogenetic relapse group. The median age of the patients was 50 years, and 55% of them had received imatinib as first-line therapy. BCR-ABL transcript levels were measured after achievement of complete cytogenetic remission (CCyR) and at 6-month intervals. RESULTS: MMR was detected in 44% patients at the start of the study. This value increased to 79% at month 36 of evaluation. Complete molecular response (CMR) also increased from 24% to 52% of patients. Not achieving a stable MMR determined a higher risk of cytogenetic relapse (9% of MMR patients not achieving an MMR vs. 1% of patients who achieved MMR). Patients with sustained MMR had a significantly better cytogenetic relapse-free survival at 48 months (97% vs. 87%; P = .008) but showed no differences in overall survival. Patients who did not remain in CCyR changed treatment. CONCLUSIONS: A stable MMR is a strong predictor for a durable CCyR. Standardized molecular monitoring could replace cytogenetic analysis once CCyR is obtained. These results emphasize the validity and feasibility of molecular monitoring in all standardized medical centers of the world.
Subject(s)
Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics , Piperazines/therapeutic use , Protein Kinase Inhibitors/therapeutic use , Pyrimidines/therapeutic use , Adolescent , Adult , Aged , Aged, 80 and over , Argentina , Benzamides , Female , Fusion Proteins, bcr-abl/genetics , Humans , Imatinib Mesylate , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/diagnosis , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/mortality , Male , Middle Aged , Neoplasm, Residual/diagnosis , Neoplasm, Residual/genetics , Prognosis , Remission Induction , Survival Analysis , Treatment Outcome , Uruguay , Young AdultABSTRACT
Un grupo de 7 hematólogos argentinos con reconocida experiencia en el tratamiento de la leucemia mieloide crónica, participó de una reunión de consenso realizada en julio de 2007, con el fin de precisar la utilización de recursos sanitarios en el manejo de dicha enfermedad, en el país. Mediante la aplicación de la técnica Delphi modificada se obtuvo elevado grado de acuerdo entre los especialistas, quienes expresaron la situación real de la práctica clínica en las diferentes regiones y ámbitos de atención, en los cuales se desempeñan. Resultaron evidentes la importante adhesión a los lineamientos terapéuticos recomendados a nivel internacional, así como la optimización de los recursos de atención de la salud disponibles. Esta información, complementada con estudios farmacoeconómicos adicionales, puede resultar de utilidad para definir planes futuros de asistencia sanitaria integrales, que permitan a los enfermos con LMC acceder a las opciones más ventajosas desde el punto de vista clínico y de la relación costo-efectividad, de modo de mejorar no sólo la tasa de supervivencia sino también su calidad de vida.
