Background: The monitoring of BCR-ABL transcript levels by real-time quantitative polymerase chain reaction\r\n(RT-qPCR) has become important to assess minimal residual disease (MRD) and standard of care in the treatment\r\nof chronic myeloid leukemia (CML). In this study, we performed a prospective, sequential analysis using RT-qPCR\r\nmonitoring of BCR-ABL gene rearrangements in blood samples from 91 CML patients in chronic phase (CP) who\r\nachieved complete cytogenetic remission (CCyR) and major molecular remission (MMR) throughout imatinib\r\ntreatment.\r\nMethods: The absolute level of BCR-ABL transcript from peripheral blood was serially measured every 4 to 12\r\nweeks by RT-qPCR. Only level variations > 0.5%, according to the international scale, was considered positive.\r\nSequential cytogenetic analysis was also performed in bone marrow samples from all patients using standard\r\nprotocols.\r\nResults: Based on sequential analysis of BCR-ABL transcripts, the 91 patients were divided into three categories:\r\n(A) 57 (62.6%) had no variation on sequential analysis; (B) 30 (32.9%) had a single positive variation result obtained\r\nin a single sample; and (C) 4 (4.39%) had variations of BCR-ABL transcripts in at least two consecutive samples. Of\r\nthe 34 patients who had elevated levels of transcripts (group B and C), 19 (55.8%) had a < 1% of BCR-ABL/BCR\r\nratio, 13 (38.2%) patients had a 1% to 10% increase and 2 patients had a >10% increase of RT-qPCR. The last two\r\npatients had lost a CCyR, and none of them showed mutations in the ABL gene. Transient cytogenetic alterations\r\nin Ph-negative cells were observed in five (5.5%) patients, and none of whom lost CCyR.\r\nConclusions: Despite an increase levels of BCR-ABL/BCR ratio variations by RT-qPCR, the majority of CML patients\r\nwith MMR remained in CCyR. Thus, such single variations should neither be considered predictive of subsequent\r\nfailure and nor an indication for altering imatinib dose or switching to second generation therapy. Changing of\r\nimatinib on the basis of BCR-ABL/BCR% sustained increase and mutational studies is a prudent approach for\r\npreserving other therapeutic options in imatinib-resistant patients.
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