The Clinical And Molecular Research On Therapeutic Effect Of TKIs In Chronic Myeloid Leukemia

1. The impact of early molecular response on long-term survival of frontline imatinib treatment of chronic myeloid leukemia patients in chronic phaseObjectiveTo investigate 5-year major molecular response(MMR) rate and complete cytogenetic response(CCy R) rate firstly and then analyze the rate of overall survival(OS), progression-free surviavala(PFS) and event-free survival(EFS) of 5-year of patients with chronic myeloid leukemia in chronic phase(CML-CP) treated with frontline imatinib. At last, we discussed impact of molecular response at 3, 6, and 12 months of patients on OS, PFS and EFS.MethodWe collected clinical data of 648 patients receiving frontline imatinib treatment of CML-CP diagnosed between July 2002 and August 2015. At first, we analyzed 5-year cumulative MMR and CCy R. Secondly, we analyzed 5-year estimated OS, PFS and EFS. Lastly, we compared difference of OS、PFS and EFS in BCR-ABL transcript levels≤10% and BCR-ABLIS≤1% according to the international scale(BCR-ABLIS) to BCR-ABLIS >10% and BCR-ABLIS >1% at 3 months and 6 months respectively. We also compared difference of OS、PFS and EFS in BCR-ABLIS ≤0.1% to BCR-ABLIS >0.1% at 12 months.ResultIn 648 CML-CP patients treated with frontline imatinib, there were 408 males and 240 males(male: female=1.7: 1). The median age was 41 years old at diagnosis(range, 5-80). Median observation time was 50 months(range, 4-162). The 5-year estimated cumulative MMR rate was 80% and CCy R was 88%. The 5-year estimated OS was 98%, PFS was 93%, and EFS was 82%. At 3 months, patients of BCR-ABLIS ≤10% had a higher PFS than BCR-ABLIS >10%(P=0.029), but there were no siginificance in OS and EFS; The groups of BCR-ABLIS ≤1% and BCR-ABLIS >1% at 3 months had no siginificance in OS, PFS and EFS. Patients of BCR-ABLIS ≤10% had better OS、PFS and EFS than BCR-ABLIS >10% at 6 months(P=0.003 、 P=0.001 、 P=0.009); BCR-ABLIS≤1% was associated with superior PFS and EFS than BCR-ABLIS >1%(P=0.005 and P=0.000 respectively), with no statistical siginificance in OS(P=0.056). At 12 months, >0.1% BCR-ABLIS was associated with inferior PFS and EFS compared with BCR-ABLIS>0.1%(P=0.020 and P=0.000 respectively), with no statistical siginificance in OS(P=0.081).ConclusionThe molecular response at 6 months in combination with at 3 months may better predict long-term survival of patients of CML-CP treated with imatinib.2. Analysis of prognostic factors in CML-CP patients receiving frontline imatinib treatmentObjectiveTo analyze prognostic factors in chronic myeloid leukemia patients treated with imatinib in chronic phase.MethodFollow-up of frontline imatinib treatment of CML-CP patients diagnosed between July 2002 and August 2015, median observation time was 50 months, and estimated EFS of five year was 82%. We divided patients into two groups. A group represented patients who experienced events in five years, and B group was patients who did not experience events in 5 years. We compared the constituent ratio of sex, age≥65years, white blood cell>100×109/L, platelet>700×109/L, high Sokal score, insufficient dose of imatinib and difference of early molecular response.ResultThere were 84 patients in A group, and 217 patients in B group. The ratio of high risk of A group was higher than B group significantly(P=0.002). The ratio of BCR-ABLIS>10% at 6 months in A group was higher than B group(P=0.014), and so was BCR-ABLIS>0.1% at 12 months(P=0.010). The two groups also had significance in the ratio of insufficient dose of imatinib(P=0.002). The two groups had no significance in the constituent ratio of sex、age≥65years、white blood cell>100×109/L、platelet>700×109/L and BCR-ABLIS>10% at 3 months.ConclusionHigh sokal score at diagnosed、insufficient dose of imatinib affected EFS of 5 years, BCR-ABLIS>10% at 6 months and BCR-ABLIS>0.1% at 12 months could indicate inferior EFS of 5 years.3. The comparation of efficacy and safety of imatinib mesylate(Gleevec) and domestic imatinib mesylate(Gnico) in the treatment of de novo chronic phase chronic myeloid leukemiaObjectiveTo compare the curative effect and safety of imatinib mesylate(Gleevec) and domestic imatinib mesylate(Gnico) in the treatment of de novo chronic myeloid leukemia in chronic phase.Method53 patients with de novo CML-CP were treated with Gnico and other 164 with Gleevec. The rate of optimal response in the 3th \6th \12th month,and the rate of complete cytogenetic response( CCy R) and major molecular response(MMR) were retrospectively compared between the two groups. We also analyzed the occurrence of hematologic toxicit and non—hematologic toxicities.ResultThere was no significant difference in the rate of optimal response in the 3th \6th \12th month between the two groups.The rate of CCy R and MMR was similar between the two groups.ConclusionImatinib mesylate(Gleevec) and domestic imatinib mesylate(Gnico) had the similar efficacy and were safety for de novo CML-CP patients.4. Clinical and prognostic significance of 3q26 rearrangements in advanced-phase chronic myeloid leukemiaObjectiveTo research the clinical feature and prognostic significance of 3q26 rearrangements in advanced-phase chronic myeloid leukemia(CML).MethodWe collected the clinical data of 104 patients of chronic myeloid leukemia who progressed into acceleration phase(AP) or blastic crisis(BC), and sorted patients into two groups according to whether 3q26 rearrangements appeared in course of diseaset. We analyzed clinical characteristics of 3q26 rearrangements 、efficacy of tyrosine kinase inhibitors(TKIs) or chemotherapy on advanced-phase CML patients with 3q26 rearrangements and survival difference of two groups after disease progressed into AP or BC.Result1. In 104 CML patiens who progressed into advanced-phase, 23 cases had 3q26 rearrangements, and 81 cases did not. In advanced-phase CML patients with 3q26 rearrangements, 2 cases were at AP, and 21 cases were at BC. In 18 BC patients with 3q26 rearregements, 9 patients were myeloid blast phase(approximately 50%), and 6 patiens were myeloid mononuclear blast phase(about 33%). 1n 23 cases with 3q26 rearrangements: 9 cases were inv(3)(q21q26)/t(3;3)(q21q26),7 cases were t(3;21)(q26;q22),and 7 cases were other 3q26 rearrangements. In 9 advanced-phase CML with inv(3)(q21q26)/t(3;3)(q21q26), 2 patients had chromosome 7 abnormalities(about 22.2%).2. 11 patients of 3q26 rearrangements had information of treatment after disease progressed into advanced phase. 6 patients received TKIs alone; 5 patiens died of disease at the 6th\9th\10th\21th\27th month respectively, and one patient was alive up to now(follow-up time was 3 months). 2 patients received single chemotherapy, and died at the 9th and 15 th month respectively. One case underwent TKIs combined with chemotherapy and died of disease after 2 months. 2 cases underwent TKIs combined with allogeneic hematopoietic stem cell transplantation; one died of relapse at the 60 th month and the other was alive(follow-up time was 32 months).The median survival time of patients with 3q26 rearrangements after progressing into AP or BC was 10 months and 38 months in patients without 3q26 rearrangements. There was significance in the median survival time of two groups(P=0.006).ConclusionPatients of chronic myeloid leukeimia at AP or BC with 3q26 rearrangements had poorer respose to TKIs and shorter median survival than patients without 3q26 abnormalities.