BCR-ABLI doubling times more reliably assess the dynamics of CML relapse compared with the BCR-ABLI fold rise: implications for monitoring and management.

Rising BCR-ABL1 transcripts indicate potential loss of imatinib response in CML. We determined whether the BCR-ABLI doubling time could distinguish nonadherence from resistance as the cause of lost response. Distinct groups were examined: (1 ) acquired clinical resistance because of blast crisis and/or BCR-ABLI mutations; and (2) documented ima-tinib discontinuation/interruption. Short doubling times occurred with blast crisis (median, 9.0 days; range, 6.1-17.6 days; n = 12 patients), relapse after imatinib dis-continuation in complete molecular re-sponse (median, 9.0 days; range, 6.9-26.5 days; n = 17), and imatinib interruption during an entire measurement interval (median, 9.4 days; range, 4.2-17.6 days; n = 12; P = .72). Whereas these doubling times were consistently short and indi-cated rapid leukemic expansion, fold rises were highly variable: 71-, 9.5-, 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 mutations who main-tained chronic phase (CP: median, 48 days; range, 17.3-143 days; 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 ac-cording to clinical context. Long doubling times observed with mutations in CP al-low time for intervention. A short dou-bling time for a patient in CP should raise the suspicion of nonadherence. (Blood. 2012; 119(18):4264-4271 ) [ABSTRACT FROM AUTHOR]