BCR-ABL1 doubling-times more reliably assess the dynamics of CML relapse compared with the BCR-ABL1 fold-rise: implications for monitoring and management
Menée sur plusieurs cohortes de patients atteints d'une leucémie myéloïde chronique et traités par imatinib, cette étude évalue l'intérêt de calculer la période de doublement des transcrits BCR-ABL1 pour interpréter la perte de réponse thérapeutique et faire la distinction entre la non adhésion des patients au traitement et l'apparition d'une récidive
Rising BCR-ABL1 transcripts indicate potential loss of imatinib response in CML. We determined whether the calculated BCR-ABL1 doubling-time could distinguish non-adherence from resistance as the cause of lost response. Distinct groups were examined, 1) acquired clinical resistance due to blast crisis (BC) and/or BCR-ABL1 mutations and 2) documented imatinib discontinuation/interruption. Short doubling-times occurred with BC relapse (median 9.0 days, range 6.1-17.6, n=12 patients), relapse after imatinib discontinuation in complete molecular response (9.0 days, 6.9-26.5, n=17) and imatinib interruption during an entire measurement interval (9.4 days, 4.2-17.6, n=12), P=.72. While these doubling-times were consistently short and indicated rapid leukemic cell expansion, fold-rises were highly variable: 71-fold, 9.5-fold and 10.5-fold, respectively. The fold-rise depended on the measurement interval, whereas the doubling-time was independent of the interval. Longer doubling-times occurred for patients with BCR-ABL1 mutations who maintained chronic phase (CP, 48 days, 17.3-143, n=29), P<.0001. Predicted short and long doubling-times were validated on an independent cohort monitored elsewhere. The doubling-time revealed major differences in kinetics according to clinical context and should be calculated in cases of increasing BCR-ABL1. Long doubling-times observed with mutations in CP allow time for intervention. A short doubling-time for a patient in CP should raise the suspicion of non-adherence.
Blood , résumé, 2012