Loss of BCR-ABL PCR-Negativity Predicts an Increased Risk of Subsequent Molecular, Cytogenetic and Hematologic Relapse in CML Patients Treated with Tyrosine Kinase Inhibitors
Martin H Luu, Carole B Rempfer, Richard D Press. Oregon Health and Science University, Portland, OR
Background: Although most chronic myeloid leukemia patients treated with tyrosine kinase inhibitors (TKIs) experience a durable complete cytogenetic and hematologic response, a subset achieves undetectable BCR-ABL transcript levels during molecular monitoring by real-time quantitative reverse transcription-polymerase chain reaction (RQ-PCR). Herein we sought to determine whether a loss of undetectable BCR-ABL transcript levels following a durable PCR-negativity is a risk factor for subsequent loss of major molecular response (MMR), or cytogenetic and/or hematologic relapse.
Design: The BCR-ABL RQ-PCR records of all CML patients tested at our medical center from 2004-2011 were reviewed. Patients with at least 36 months of molecular monitoring while on TKIs and three consecutive undetectable BCR-ABL transcript levels were included in this study. Patients with less than 12 months of follow-up were excluded from the study. The clinical course of patients who maintained a durable PCR-negativity was compared to those who lost undetectable BCR-ABL transcript levels following three consecutive negative RQ-PCRs. Categorical analysis was performed using the Fisher exact test and a p-value <0.05 was considered significant.
Results: A total of 7532 BCR-ABL RQ-PCRs for 1617 CML patients were performed from 2004-2011. Of these patients, 159 (9.8%) had at least 36 months of molecular monitoring with three consecutive negative RQ-PCRs. The vast majority of patients (125; 78.6%) maintained a durable undetectable BCR-ABL PCR after an average of 48 (SD ± 19) months of follow-up. 34 (21.4%) patients, however, lost undetectable BCR-ABL PCR after attaining PCR-negativity. Of these 34 patients, a significant fraction (11; 32.4%) experienced a loss of MMR (International Scale > 0.1%) compared to no such events in the durable PCR-negative group (p < 0.001). Two patients who lost MMR either experienced cytogenetic relapse or progressed to acute leukemia versus no such patient who maintained durable PCR-negativity (p = 0.006).
Conclusions: A high proportion of CML patients who achieve BCR-ABL PCR-negativity during TKIs therapy maintained this PCR-negativity and remained in remission. However, patients who lost PCR-negativity during molecular monitoring were at a significant risk for a subsequent molecular, cytogenetic, and/or hematologic relapse.
Wednesday, March 21, 2012 9:30 AM
Poster Session V # 217, Wednesday Morning