Molecular Monitoring of Imatinib in Chronic Myeloid Leukemia Patients in Complete Cytogenetic Remission: Does Achievement of a Stable Major Molecular Response at any Time Point Identify a Privileged Group of Patients? A Multicenter Experience in Argentina

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• 作者：Carolina Pavlovsky¹ ; ^{cpavlovsky@fundaleu.org.ar} ; Isabel Giere¹ ; Beatriz Moiraghi² ; Miguel A. Pavlovsky¹ ; Pedro Negri Aranguren³ ; Juan Garcí ; a⁴ ; Isolda Fernandez¹ ; Raquel Bengió ; ⁵ ; Jorge Milone⁶ ; Valentin Labanca⁷ ; Rosario Uriarte⁸ ; Virginia Lombardi¹ ; Fernanda Garcí ; a Reinoso¹ ; Alicia E. Magariñ ; os⁹ ; Lem Martinez⁸ ; Hé ; ctor Murro¹⁰ ; Francisco Lastiri¹¹ ; Santiago Pavlovsky¹
• 关键词：Minimal residual disease ; Prognostic factors ; Real-time quantitative polymerase chain reaction ; Tyrosine kinase inhibitors
• 刊名：Clinical Lymphoma Myeloma and Leukemia
• 出版年：2011
• 出版时间：June 2011
• 年：2011
• 卷：11
• 期：3
• 页码：280-285
• 全文大小：338 K

文摘

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.