Prognostic Value Of BCR-ABL And Clinical Significance Of ABL Kinase Domain Mutation After TKIs

(?)Prognostic value of BCR-ABL at 3 and 6 months after imatinib treatment of chronic myeloid leukemiaObjective:To investigate the value of imatinib in the treatment of chronic myelocytic leukemia(CML)3 and 6 months after BCR-ABL transcript level,and to provide evidence for early intervention in CML patients.Methods:A total of 700 newly diagnosed chronic CML patients treated in the Department of Hematology,First Hospital Affiliated of Suzhou University from January 2011 to June 2014 were enrolled.All patients were treated with imatinib for 2 years.And above,the cumulative drug reduction and withdrawal time is within 2 weeks.All patients were examined before treatment,including peripheral blood cell classification,bone marrow cell morphology,conventional bone marrow chromosome,and qPCR to detect BCR-ABL fusion gene.The Sokal score was calculated based on age,spleen size,platelet count,and number of primordial cells.The patient received oral imatinib 400 mg/d,once a week for blood routine examination,once every 2 weeks after hematologic remission,and bone marrow chromosome and BCR at 3,6,12,18,and 24 months after treatment initiation.ABL fusion gene.According to the early molec-ular reaction(EMR:BCR-ABL?10%at 3 months),the cumulative CCyR and MMR were compared between different subgroups of EMR and non-EMR groups and non-EMR groups.Results:According to the analysis of Sokal score,164 cases(23.43%)were at high risk,348 cases(49.71%)were at risk,and 188 cases(26.86%)were at low risk.In this study,369 cases(52.71%)did not reach EMR,331(47.29%),so the patients were divided into EMR group and non-EMR group.The bone marrow chromosomes of CML patients at different time points after imatinib treatment were detected.In EMR group,176,219,336,347,358 cases obtained CCyR;at 3,6,12,18 and 24 months,respectively.In the non-EMR group,0,22,95,168 and 190 cases obtained CCyR at 3,6,12,18 and 24 months,respectively.In 10 cases of EMR group and 130 cases of non-EMR group,no CCyR,map was observed at the end of 24 months.More patients in EMR group reached CCyR,at different time points than those in non-EMR group(P<0.05).The expression of BCR-ABL in CML patients was detected by qPCR at each time point after imatinib treatment.MMR;was obtained in 0,64,224,305 and 332 cases in EMR group at 3,6,12,18 and 24 months,respectively.MMR was obtained in 0,0,28,79 and 101 cases of non-EMR group at 3,6,12,18 and 24 months,respectively.In EMR group(n=7)and non-EMR group(n=41),no MMR,map was observed for 24 months.Compared with the non-EMR group,more patients in the EMR group reached MMR,at different time points,and there was significant difference between the two groups(P<0.05).Patients who did not achieve EMR were divided into BCR-ABL<1%(group ?),1%-10%(group ?),and>10%(group ?)according to the BCR-ABL level at 6 months.In the subgroup,12 months of CCyR and 18 months of MMR were compared with the EMR group(group I).The results showed that patients who did not achieve EMR in 6 months of BCR-ABL?1%of patients had 12-month CCyR and 18-month MMR and EMR groups were not statistically different(P>0.05),while BCR-ABL was 1%?There were significant differences between the 10%group and the>10%group and the EMR group(P<0.05).Conclusion:BCR-ABL ?1%6 months after failure of EMR and EMR after treatment with imatinib in patients with CML can predict a good prognosis,which is presumed to be one of the basis for early intervention.(?)Clinical analysis of imatinib,nilotinib and dasatinib in patients with newly diagnosed chronic myeloid leukemia.Objective:to compare the efficacy of imatinib,nilotinib and dasatinib in the treatment of newly diagnosed chronic myeloid leukemia(CML).Methods:from Jan 2016 to April 2017,364 patients with CML were selected from Department of Hematology,First Hospital Affiliated of Suzhou University.The diagnostic criteria were evaluated according to the guidelines for the diagnosis and treatment of chronic myeloid leukemia in China in 2016.According to the different drugs for the treatment of TKI,they were divided into three groups:imatinib treatment group,nilotinib treatment group and dasatinib treatment group.According to the complete hematological response(CHR),obtained in 3 months,the partial cytogenetic response(PCyR),was obtained in 6 months,the complete cytogenetic response(CCyR)was obtained in 12 months,and the main molecular response(MMR),was obtained in 18 months.The difference of curative effect among the three groups was analyzed.At the same time,the adverse reactions of the three groups were analyzed to evaluate the safety of the drug.Results:the complete cytogenetic response(CCyR)and major molecular response(MMR),in nilotinib group and dasatinib group were significantly different from those in imatinib group(p<0.05).The therapeutic effect of nilotinib was better than that of dasatinib.The percentage of complete cytogenetic response(CCyR)in patients with chronic phase 12 and 18 months after treatment with nilotinib was 87.21%and 89.53%,respectively,which was significantly higher than that in imatinib group(p<0.05).Similarly,the main molecular response(MMR),in the nilotinib treatment group was significantly higher than that in the imatinib treatment group(p<0.05).The above results showed that the improvement effect of nilotinib was more obvious in patients with chronic CML.At the same time,the cumulative incidence of hematological adverse reactions of nilotinib and dasatinib was significantly lower than that of imatinib group(p<0.05).Conclusion:the efficacy of nilotinib and dasatinib in the treatment of CML is better than that of imatinib,and there are few hematological adverse reactions.(?)Detection of ABL kinase mutation and its clinical significance.Objective:to explore the detection and clinical significance of ABL kinase mutation.Methods:a total of 368 patients with CML treated in the Department of Hematology,affiliated Hospital of Nantong University from January 2014 to April 2017 were selected,including 58 patients with IM resistance in CML.The patients were divided into four groups:IM resistant mutation group,IM resistant non-mutation group,IM non-resistant mutation group and IM non-resistant non-mutation group,and BCR-ABL kinase region mutation and Sokal score were detected by q-PCR.To analyze the effect of BCR-ABL kinase region mutation on drug resistance and survival of patients.Results:a total of 12 ABL kinase region mutations were detected in 58 IM resistant patients.In the IM resistant mutation group,3 patients were in the chronic phase of(CP),4 in the accelerated phase of(AP)and 5 in the acute phase of(BP);.Compared with CP,the frequency of KD mutation in AP/BP was higher and increased with the duration of the disease.The mutation types of ABL kinase region were found in 12 patients,including T315I mutation 8.62%,F317L,M244V,F359V and E255V mutation 3.45%(2/58).The incidence of mutations in G250E,V299L,F359C,L384M,H396R,Y253H,E459K and M351T was 1.72%(1/58).The mutation of ABL kinase region was positively correlated with Sokal score,and the patients without mutation had better progression-free survival.The median follow-up time of 58 patients was 40.5(6.0-108.0)months.The EFS rate and OS rate in drug-resistant mutation group were 33.3%(4/12)and 75%(9/12),respectively.The 60-month EFS rate and OS rate in drug-resistant non-mutation group were 71.17%(33/46)and 78.26%(36/46),respectively.The EFS rate in drug-resistant mutation group was significantly higher than that in drug-resistant non-mutation group(P<0.0432).However,there was no significant difference in OS rate between drug-resistant mutation group and drug-resistant non-mutation group(P>0.6532).Conclusion:mutation detection is beneficial to early intervention and timing change of TKI in some patients.Mutation detection is of great clinical significance in patients with loss of efficacy,poor efficacy or any signs of disease progression.