We would like to express our gratitude to all the study participants and their families, and the study investigators at participating study sites. included 139 individuals receiving imatinib, 169 receiving nilotinib, and 144 receiving dasatinib. Comorbidities were diagnosed in 99 patients. CCI scores were stratified as follows: 2, 353 patients; 3, 72 patients; and?4, 27 patients. Treatment response did not vary relative to CCI scores. However, across the entire cohort, the OS rate was significantly lower among patients with higher CCI scores than in those with a CCI score of 2 (94.4% in score 2, 89.0% in score 3, and 72.8% in score?4; transcript [international scale (Is usually) 0.1%], and MR4.5 was defined as a 4.5\log reduction of the transcript (IS??0.0032%). IS was regularly monitored every 3?mo in the first 12 months and every 6?mo thereafter using the MolecularMD One\Step qRT\PCR kit (BML Inc, Kawagoe, Japan). AEs related to the TKIs were graded according to the Common Toxicity Criteria of the National Malignancy Institute (NCI\CTC) version 4.03. This study used the CCI score 6 (without considering the age factor) to evaluate the impact of comorbidity itself at diagnosis of CML\CP around the clinical outcome. Patients were classified into CCI risk groups 2, 3, and?4 for Lomeguatrib analysis according to the total scores. The lowest CCI score of 2 was based on CML. The AA\CCI score was derived by adding one point to the summed CCI scores for each decade of age over 40. 6 2.4. Statistical analysis Chi\square test and Wilcoxon rank\sum test were used to compare clinical characteristics for categorical data and continuous data, respectively. OS rates were calculated using the Kaplan\Meier method and compared using the log\rank test. Gray’s test was used to compare cumulative incidence curves. Cox proportional hazard analyses were performed to determine prognostic indicators of OS. Wald test was conducted to assess the prognostic significance of a candidate single variable. Statistical analyses were performed using EZR, 11 a graphical user interface for R (R Foundation for Statistical Computing, Vienna, Austria). All hypothesis screening was two\tailed with a significance level of Is usually??0.01%), or MR4.5 (IS??0.0032%) was a critical milestone for the eligibility criteria in the treatment\free remission trial. 13 , 14 , 15 , 16 , 17 Patients with comorbidities should avoid long\term TKI treatment because of late\onset toxicities, such as cardiovascular events or pulmonary toxicities, and TKI cessation for treatment\free remission might be considered whenever possible. No differences in reaching MR4.5 were reported in relation to the AA\CCI risk score in patients with CML treated with imatinib. 8 We also exhibited that this cumulative Lomeguatrib incidence of MR4.5 at 36?mo and the median time to MR4.5 (961?d in the imatinib cohort vs. 724?d in the 2GTKI cohort; P?=?.12) were similar among patients with a CCI score of 3 treated with imatinib or a 2GTKI, but no patient with a CCI score of?3 from your imatinib cohort GRF55 achieved MR4.5 at 36?mo (0% in the imatinib cohort vs. 34.1% in the 2GTKI cohort; P?=?.13). These results from our study Lomeguatrib indicated that a DMR and the possibility of treatment\free remission could be achieved even in patients with comorbidities by treatment with 2GTKIs in clinical practice. Some recent studies were Lomeguatrib focused on reduced TKI dosing. 18 , 19 , 20 Naqvi et al observed a favorable response rate in patients with CML\CP treated with dasatinib at a daily dose of 50?mg, compared with the response in those patients treated with dasatinib at a standard daily dose of 100?mg, as shown in the DASISION study, although the study design was limited to a single\arm phase 2 trial. 18 The lower rates of toxicities, including pleural effusion and interruption due to AEs were also observed in a cohort receiving dasatinib at a daily dose of 50?mg, compared with those in Lomeguatrib the classical control of the DASISION trial (dasatinib at a daily dose of 100?mg). 3 Furthermore, the De\Escalation and Stopping Treatment with Imatinib, Nilotinib, or sprYcel (DESTINY) trial exhibited that this de\escalation of TKI dosing.