Prospective long-term minimal residual disease monitoring using RQ-PCR in RUNX1-RUNX1T1-positive acute myeloid leukemia: results of the French CBF-2006 trial

• Published in: Haematologica (Roma) Vol. 101; no. 3; pp. 328 - 335
• Main Authors: Willekens, Christophe, Blanchet, Odile, Renneville, Aline, Cornillet-Lefebvre, Pascale, Pautas, Cécile, Guieze, Romain, Ifrah, Norbert, Dombret, Hervé, Jourdan, Eric, Preudhomme, Claude, Boissel, Nicolas
• Format: Journal Article
• Language: English
• Published: Italy Ferrata Storti Foundation 01-03-2016
• Subjects: Adaptor Proteins, Signal Transducing - genetics; Adaptor Proteins, Signal Transducing - metabolism; Adolescent; Adult; Antineoplastic Agents - therapeutic use; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Blood Cells - metabolism; Blood Cells - pathology; Bone Marrow - metabolism; Bone Marrow - pathology; Cancer; Chromosomes, Human, Pair 22; Chromosomes, Human, Pair 8; Consolidation Chemotherapy - methods; Core Binding Factor Alpha 2 Subunit - genetics; Core Binding Factor Alpha 2 Subunit - metabolism; Cytoskeletal Proteins - genetics; Cytoskeletal Proteins - metabolism; Female; France; Gene Expression; Humans; Leukemia, Myeloid, Acute - diagnosis; Leukemia, Myeloid, Acute - drug therapy; Leukemia, Myeloid, Acute - genetics; Leukemia, Myeloid, Acute - mortality; Life Sciences; Male; Middle Aged; Monitoring, Physiologic; Neoplasm, Residual; Prospective Studies; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins - metabolism; Real-Time Polymerase Chain Reaction; Recurrence; Remission Induction; RUNX1 Translocation Partner 1 Protein; Survival Analysis; Transcription Factors - genetics; Transcription Factors - metabolism; Translocation, Genetic
• ISSN: 0390-6078; 1592-8721
• DOI: 10.3324/haematol.2015.131946

In t(8;21)(q22;q22) acute myeloid leukemia, the prognostic value of early minimal residual disease assessed with real-time quantitative polymerase chain reaction is the most important prognostic factor, but how long-term minimal residual disease monitoring may contribute to drive individual patient decisions remains poorly investigated. In the multicenter CBF-2006 study, a prospective monitoring of peripheral blood and bone marrow samples was performed every 3 months and every year, respectively, for 2 years following intensive chemotherapy in 94 patients in first complete remission. A complete molecular remission was defined as a (RUNX1-RUNX1T1/ABL1)×100 ≤ 0.001%. After the completion of consolidation therapy, a bone marrow complete molecular remission was observed in 30% of the patients, but was not predictive of subsequent relapse. Indeed, 8 patients (9%) presented a positive bone marrow minimal residual disease for up to 2 years of follow-up while still remaining in complete remission. Conversely, a peripheral blood complete molecular remission was statistically associated with a lower risk of relapse whatever the time-point considered after the completion of consolidation therapy. During the 2-year follow-up, the persistence of peripheral blood complete molecular remission was associated with a lower risk of relapse (4-year cumulative incidence, 8.2%), while molecular relapse confirmed on a subsequent peripheral blood sample predicted hematological relapse (4-year cumulative incidence, 86.9%) within a median time interval of 3.9 months. In t(8;21)(q22;q22) acute myeloid leukemia, minimal residual disease monitoring on peripheral blood every 3 months allows for the prediction of hematological relapse, and to identify patients who could potentially benefit from intervention therapy. (ClinicalTrials.gov ID #NCT00428558).