Follw up until achievement of CCyR No get PD173074 change Dose escalation Dose reduction Loss of CCyR Alteration in Ph negative cells Achievement of CMR 19 13 2 68 18 5 2 5 39 0 0 0 45 9 3 0 4 29 19 11 0 21 7 2 0 1 10 0 2 2 2 2 0 2 0 0 Group A (n 57) Group B (n 30) Group C (n 4)Serpa et al. BMC Blood Disorders 2010, 10:7 http://www.biomedcentral.com/1471-2326/10/Page 5 ofAmong the 39 patients with CMR, 12 were pretreated with IFN-a: eight in group A, and four in group B. There was no difference in response rate to imatinib between the group that were pre-treated with IFN-a, or those that did not have IFN-a before. Our follow-up cytogenetic evaluations revealed five (5.5 ) patients with chromosomal abnormalities in Ph-negative cells (Table 2). Of these, three patients (two in group A and one in group B) had developed trisomy 8, one patient had inv(9) (group A), and one had monosomy 7 (Group A). These cytogenetic alterations were transient in four patients (lasting 6 to 40 months), and none of the five patients lost CCyR.Discussion Since the introduction of imatinib in 1998, there has been a significant decline of 30 in treatment-related mortality for patients exposed to therapy compared with a historical control group of CML patients who underwent stem cell transplantation prior to the availability of imatinib [34]. Following the introduction of imatinib as first-line therapy for patients with CML, CCyR has become a more frequent event in these patients (> 85 ), and there has been a dramatic improvement of overall survival (98 ) and progression-free survival (99 ) with the achievement of CCyR after PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/27597769 18 months of treatment, compared with 76 overall and 87 progression-free survival, with partial cytogenetic response [16,35,36]. Several studies have reported that patients with both CCyR and MMR have lower rates of CCyR loss. Some reported higher event-free survival compared with those who achieved CCyR but not MMR [16,37-39]. Several researchers have found greater progression-free survival in patients with MMR [23,32,40], but others have not supported this observation [16,36,39]. The impact on overall survival has not been confirmed [36,38], but the change of treatment to a second-generation inhibitor soon after the loss of CCyR may explain this lack of relevance to overall survival. In this report, we investigated the potential of RTqPCR measurement of BCR-ABL transcript levels to predict cytogenetic relapse by monitoring the BCR-ABL transcript every 4 to 12 weeks throughout imatinib treatment in 91 CP-CML patients who had achieved CCyR and MMR. At least one variation in RT-qPCR and relapse developed at the molecular level were detected in 34 (37.3 ) patients and only 4 (group C) had variations of BCR-ABL transcripts in consecutives samples. The raise in BCR-ABL/BCR ratio was common even in patients who had achieved CMR. The only two patients who had a > 10 increase, were also the only two who lost CCyR. Overall, these findings indicate that a rising trend of BCR-ABL transcripts is more meaningful than a single elevation. Of note, one of these patientsappeared to have become refractory not only to imatinib but also to nilotinib and bosutinib. The patient was confronted with the results of the laboratory follow-up and then admitted therapy noncompliance. Thus, in addition to technical variation, drug resistance and treatment failure during imatinib therapy, a rise in BCR-ABL transcript may indicate inadequate imatinib dose, particularly a lack of pat.
