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The Cytogenetic And Targeted Treatment Study Of Chronic Myeloid Leukemia

Posted on:2016-08-12Degree:MasterType:Thesis
Country:ChinaCandidate:Y H YueFull Text:PDF
GTID:2284330464951424Subject:Internal Medicine
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1. The clinical and laboratorial characteristics of 2384 patients with chronic myeloid leukemia in a single centerObjectivesThis study aimed to analyse systematically the clinical characteristics of chronic myeloid leukemia patients and to reveal the unique features of CML patients in our area.MethodsThe clinical information of 2384 chronic myeloid leukemia patients from 2004 to 2014 was collected to analyse the chromosome abnormalities, clinical characteristics and the types of BCR-ABL of chronic myeloid leukemia patients.ResultsIn recent ten years, of 2384 chronic myeloid leukemia patients in our area, the median age was 42(range, 4-89) years old, males more than females(M:F 1.55:1), 84.3% in chronic phase, 15.7% in accelerated phase or blast crisis. 66.67% of the blast crisis patients had progressed to acute myeloid leukemia. Of 2384 patients, 80.63% with classic t(9;22) translocation, 5.92% with variant translocations, 6.28% with additional chromosomal abnormalities. In addition to chromosomes 9 and 22, the most involved chromosome was chromosome 1(13 cases,11.50%) and 6(11cases,9.73%)in patients with variant translocations. While in those with additional chromosomal abnormalities, the most common additional chromosomes were chromosome Ph(12 cases,10%),+8 and der(9)(9 cases,7.5%, respectively),der(22)(8 cases,6.67%),+19 and-Y(7 cases,5.83%, respectively). The majority of BCR-ABL was P210(98.87%), the minority was P190(about 1%).ConclusionPatients from our center with CML were younger(median age, 42) compared with those(ages, 50-60) in western countries and similar to those(ages, 35-40) in India. The number of new diagnosed patients in accelerated phase or blast crisis was higher than that in western countries. The majority of the blast crisis patients had progressed to acute myeloid leukemia. The chromosomal abnormalities and the types of BCR-ABL in our center were similar to those in western countries.2. The influence of additional chromosomal abnormalities on the TKIs treatment of CML-CP patientsObjectivesTo explore the influence of classic t(9;22) translocation, variant translocations and additional chromosomal abnormalities on the TKIs treatment of CML-CP patients.MethodsWe reviewed the clinical and laboratorial information of 589 CML-CP patients with the treatment of TKIs, who came to our hospital and had the karytypes at diagnosis between May 2009 and October 2014. 589 CML-CP patients were divided into five groups according to the karyotypes at diagnosis. The patients consisted of 474(80.48%) patients with classic t(9;22) translocation, 40(6.79%) patients with variant translocations, 32(5.43%) patients with additional chromosomal abnormalities, 35(5.94%) patients with normal karyotype and 8(1.36%) patients with other abnormal karyotypes. The PFS, EFS, CI of MMR and CI of CCy R were calculated using the Kaplan-Meier method and compared using the log-rank text by SPSS17.0. The χ-square tests were used for the molecular level comparisons at 3, 6, 12 months among the five groups.Results1. As far as the molecular optimal response after TKIs treatment of 3 months, 6 months or 12 months, the difference between the group with additional chromosomal abnormalities and the one with t(9;22) at 3 months and 6 months were both significant(50% vs 73.94%,P=0.0170;50% vs 72.05%,P=0.0354, and the difference between the group with variant translocations and the one with t(9;22)was significant at 6 months(53.3% vs 72.05%,P=0.0316).2. Five groups showed similar PFS and OS. The P value of CI of CCy R(P=0.0163) and EFS(P=0.0010) was statistically significant among five groups. Compared with other groups, the patients with additional chromosomal abnormalities presented the worst results of EFS(75.03%), CI of MMR(59.66%) and CI of CCy R(47.25%). What’s more, the difference between the group with additional chromosomal abnormalities and the one with t(9;22)had the statistical significance for CI of CCy R(47.25% vs 84.01%,P=0.0103) and EFS(75.03% vs 90.01%,P=0.0006).ConclusionThe additional chromosomal abnormalities influence the efficiency of TKIs. As far as the molecular optimal response after TKIs treatment, the difference between the group with t(9;22)and the one with additional chromosomal abnormalities at 3 months and 6 months were both significant. The P value of CI of CCy R and EFS was statistically significant among five groups. What’s more, the difference between the group with additional chromosomal abnormalities and the one with t(9;22)had the statistical significance for CI of CCy R and EFS.3. The sequential treatment and prognosis of CML-CP patients with a warning response after 3 months of imatinib treatmentObjectivesTo explore whether to change therapy for those CML-CP patients with a warning response after 3 months of imatinib treatment and the difference between the group of switching to nilotinib and the continuing imatinib group.MethodsSeptember 2009 and August 2014, 495 newly diagnosed CML-CP patients who underwent imatinib treatment and who were monitored in our institute were identified and followed up. The follow-up time ended in October 2014. Among them, 46 patients have BCR-ABL1 IS >10% with a warning response and 71 patients have BCR-ABL1 IS >10% with a failure response at 3 months. Of 71 patients with a failure response, 25(IM-F)cases continued imatinib treatment(400-600mg/d),46( Nilot-F) cases switched to nilotinib(300 or 400 mg, bid); and of 46 patients with a warning response,26( IM-W) cases continued imatinib treatment(400-600mg/d), 20( Nilot-W) switched to nilotinib(300 or 400 mg, bid)。We analysed the clinical and laboratorial characteristics of 46 patients in detail. The PFS, EFS, cumulative incidence(CI) of major molecular response(MMR), cumulative incidence(CI) of molecular response 4.0(MR4.0) were calculated using the Kaplan-Meier method and compared using the log-rank text by SPSS17.0. The χ-square tests were used for the short-term molecular level comparisons between the two groups.Results1. The molecular response of 117 CML-CP patients with BCR-ABL1 IS >10% showed, that, compared with Nilot-F group, Nilot-W group showed significantly higher percentage achieving BCR-ABL1<10% at 3 months of nilotinb treatment(90% vs 47.83%, P=0.0013); what’s more, compared with IM-W group, Nilot-W group showed significantly higher percentage achieving BCR-ABL1<1% at 6 months(85%vs 19.23%, P=0.0004); better cumulative rate of MMR and MR4.0 of 4 years were achieved in Nilot-W group compared with IM-W group(41.2% vs. 82.1%, p=0.0091; 18.6% vs 61.5%, P=0.035), the same was in Nilot-W group compared with Nilot-F group(82.1% vs.30.24%, p=0.0003; 61.5% vs 19.85%, P=0.0018).2. The survival analysis of 117 CML-CP patients with BCR-ABL1 IS >10% revealed, that, the PFS of 4 years in Nilot-W group was higher compared with IM-W group(100% vs. 80.01%, P=0.2826), Nilot-W group vs Nilot-F group(100% vs.87.66%, P=0.1218);the EFS of 4 years in IM-W group was higher compared with Nilot-W group(80.01% vs.68.45%, P=0.4378), Nilot-W group vs Nilot-F group( 68.45% vs.81.06%, P=0.6846).ConclusionThe CML-CP patients switching to nilotinib were able to acquire deeper molecular remission than those continuing imatinib, who had a warning molecular reponse BCR-ABL1IS>10% after 3 months of imatinib treatment.
Keywords/Search Tags:chronic myeloid leukemia, clinical and laboratorial characteristics, Key Points: chronic myeloid leukemia in chronic phase, additional chromosomal abnormalities, TKIs treatment, imatinib, nilotinib, molecular response
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