Clinical And Genetic Factors Affecting The Efficacy Of Chronic Myeloid Leukemia In TKIs Era

1.clinical characteristics of 1075 patients with chronic myeloid leukemia (CML)in a single center and the prognosis of the patients with additional chromosomal abnormalities(ACAs)ObjectiveTo analyze the basic clinical features of CML patients in our center.To investigate the effect of different karyotypes such as classic translocation,variant translocations and ACAs on the efficacy of TKIs and outcome of CML-CP patients.To analyze the differences in prognosis of CML patients with different ACAs numbers and typesMethod1.We retrospectively collected the basic clinical and laboratory data of 1 075 patients with CML from 2010 to 2016,and analyzed the clinical features ? chromosome abnormalities and the types of BCR-ABL1 transcript among them.2.The clinical data of 1042 CML-CP patients from 2010 to 2016 were collected and divided into 6 groups according to karyotypes at diagnosis.,the classical translocation,variant translocation,major-route ACAs(including +8?+Ph?i17q?+19),minor-route ACAs,the karyotype of-Y,normal karyotype.Graphpad5.0 software was used to analyze and compare the cumulative CCy R,cumulative MMR,PFS,EFS and OS among different groups by Kaplan-Meier method and Long-rank test.3.We collected the clinical characteristics of the six most common single ACAs and compared their(except for i17 q and-7/7q-)correlation with survival from the times of diagnosis or ACAs emergence.According to the prognostic significance,they fall into two groups.The patients were divided into several groups according to the numbers of ACAs at diagnose or during the disease and were compared OS from the diagnosis and ACAs emergence.Result1.The clinical characteristics of 1075 CML patients in our center in the past six years were as follows,the median age was 44 years old,males more than females,91.7% in chronic phase,8.3% in advanced phase.The main type of the blast crisis patients was acute myeloid leukemia.Among the 1075 patients,85.67% with classic translocation,6.42%with variant translocations,7.44% with ACAs.In addition to chromosomes 9 and 22,the most involved chromosomes were chromosome 1(14.49%)and 11(11.59%)in patients with variant translocations.The most common ACAs at diagnosis were +8,+Ph,-Y and+19,accounting for 13.75%,13.75%,13.75%,5% respectively.The majority of BCR-ABL1 transcript were P210,P190 and other rare types accounted for only 1.41%.2.According to the karyotypes at diagnosis,these patients are divided into several groups: the classic type,variation type,the major-route ACAs,the minor-route ACAs,-Y respectively.1-year cumulative CCy R of the 5 groups were 69%?55%?67%?64%?78%;2-year cumulative MMR were 71%?65%?49%?50%?68%;4-year PFS were 94%?93%?88%?92%?88%;4-year EFS were 69%?81%?80%?72%?57%;4-year OS were 95%?94%?100%?92%?88%;however,there were no significant differences in CCy R?MMR ?PFS?EFS and OS among these groups.3.There were several common single ACAs karyotypes,including-Y(14.58%),3q26rearrangements(14.58%),+Ph(11.46%),+8(8.33%).According to the prognostic significance,-Y ? +Ph ? +8 fall into good prognosis group(group 1),and 3q26 rearrangements into poor prognosis group.The patients were divided into four groups according to the numbers of ACAs appeared at diagnose or during the disease for the first time: 0ACA?1ACA?2ACAs and > 2ACAs,meanwhile 1ACA group was divided into group 1 and group 3q26.From the time of diagnosis and ACAs emergence,the median survival time of group 1 and group 0ACA were similar,followed by group 2 ACAs and >2 ACAs,group 3q26 was the shortest.There was significant difference among them(p<0.001).Conclusion1.CML patients in our center were younger(median age was 44)than those in western countries.The number of newly diagnosed patients in advanced phases was lower than that in western areas.The main type of the blast crisis patients was acute myeloid Resultleukemia.The types of primary karyotype and the fusion gene are similar to those data of the western countries..2.The major-route ACAs emerging at initial diagnosis had no effect on efficacy of TKIs and prognosis in CML-CP patients.3.The prognosis of CML patients is related to the numbers and the types of ACAs.3q26 rearrangement is an independent prognosis factor.2.Clinical characteristics and prognosis of 3q26 rearrangements in chronic myeloid leukemiaObjectiveTo evaluate the clinical and prognostic significance of 3q26 rearrangements in CML.MethodWe collected the clinical and laboratory data of 1 075 patients with chronic myeloid leukemia who were diagnosed from January 2010 to December 2016 and divided them into two groups with or without 3q26 rearrangements.We also compared survival of patients between the two groups.Result1.There is no difference in the age of the first diagnosis and sex ratio between the CML patients with and without 3q26 rearrangements.The patients with 3q26 rearrangements were more in the BP and needed shorter time from CP and AP advanced to BP.In the progress of blast crisis,they were mainly myeloid blast type.The quantitative results showed that the expression of EVI1 in the rearrangement positive group was significantly higher than that of the negative group.2.There is significant difference in the median overal survival time between the groups of CML with and without 3q26 rearrangements mono treated with TKIs(p<0.001).The median overal survival time of patients with 3q26 rearrangements was 11 months,while the other has not been reached.In group of CML with 3q26 rearrangements,4 cases were mono treated with TKIs,3 cases with TKIs combined chemotherapy and 2 cases with allogeneic hematopoietic stem cell transplantation.The OS of the three groups was not statistically significant(P=0.086),and the survival time of the patients in thetransplantation group was longer than that in the mono TKIs group(P=0.049).Conclusion1.3q26 rearrangements can appear in different phases in CML,but mainly in BP.If the patients with 3q26 rearrangements in CP or AP,they had a high risk of transformation to BP.2.CML patients with 3q26 rearrangements had shorter median survival time than patients without 3q26 rearrangements under mono TKIs treatments.These patients should carry hematopoietic stem cell transplantation as soon as possible.