Prognostic Value Of Early BCR-ABL Transcript Levels In Patients With Chronic Phase Of Newly Diagnosed Chronic Myeloid Leukemia

Objective:To study the relationship between 3-month and 6-month BCR-ABL transcript levels and long-term prognostic index MR4.5 in patients with a initial diagnosis of chronic myeloid leukemia（CML-CP）treated with tyrosine kinase inhibitor（TKI）,and to explore the factors affecting MR4.5 acquisition.Methods:Clinical data of 58 patients initially diagnosed with CML-CP and receiving first-line treatment with imatinib and nilotinib were analyzed from 2014 to 2022 in the Department of Hematology,Affiliated Hospital of Chifeng University.Peripheral blood BCR-ABL^IS value,age,gender,Sokal risk grade and other data were collected.MR4.5（BCR-ABLIS≤0.0032%）was used as the prognostic observation index,and the difference between BCR-ABL transcript level and subsequent MR4.5 at 3 and 6 months after TKI treatment was compared.The cumulative MR4.5 rate was plotted by Kaplan-Meier（K-M）curve,and the Log-rank test was used for the between-group comparison.Variables such as age,sex,first-or second-generation drug therapy,Sokal grade,BCR-ABL transcript levels at 3 and 6 months were included to construct a multivariate Cox proportional risk model to determine the factors affecting MR4.5 gain.Drug-related adverse effects were observed and counted at follow-up.Results:1、The proportion of patients who achieved EMR at 3 months was higher than that of patients who did not achieve EMR at 36 months（P=0.006）,and the proportion of patients who achieved EMR at 6 months was higher than that of patients who did not achieve EMR at 24 months and 36 months（P1=0.002,P2<0.001）.2、The BCR-ABL^IS values at 3 months were divided into three groups:≤1%,1%-10%,and>10%,and it was found that the proportion of BCR-ABL^IS≤1%patients reaching MR4.5 at 3 months was higher than that of>10%（P=0.004）.Similarly,BCR-ABL^IS values at 6 months were divided into three groups:≤0.1%,0.1%-1%,and>1%,and it was found that the proportion of patients with BCR-ABL^IS≤0.1%at 6months had the highest cumulative MR4.5（P1<0.001,P2<0.001）.3、By multivariate Cox regression,there was no significant effect of age,sex,first-or second-generation drug treatment,and Sokal grade on MR4.5 at initial diagnosis（P>0.05）,while BCR-ABLIS transcript levels at 3 and 6 months were independent influencing factors for MR4.5（P1=0.006,P2<0.001）.Conclusion:1、Patients who achieve EMR at 3 months and 6 months are more likely to achieve MR4.5,that is,patients who obtain EMR in the early stage are more likely to obtain remission of deep molecular response.2、Patients with BCR-ABL^IS≤0.1%at 6 months were more likely to achieve MR4.5 at follow-up time points,which may be a new indicator for early assessment of the possibility of drug withdrawal.