Analysis Of The Efficacy After Discontinuation Of Tyrosine Kinase Inhibitors Treatment In Patients With Chronic Myelogenous Leukemia

Objective To investigate the efficacy after discontinuation of tyrosine kinase inhibitors(TKI)treatment in patients with chronic myelogenous leukemia(CML).Methods A clinical dates of 582 patients with CML receiving TKI treatment in the Institute of Hematology,Fujian Medical University Union Hospital from June 2009 to December 2016,were analyzed retrospectively.Among these patients,50 cases were discontinued,so we will evaluate the curative efficacy of withdrawal of the 50 patients.Results 1.To the end of follow-up,50 patients of CML discontinued the treatment of TKI,and the median time of follow-up was 39 months(range 4 months to 97 months).At the time point of withdrawal,7 cases(14%)was at major molecular response(MMR).3 cases(6%)was at molecular response 4.0(MR4.0).1 cases(2%)was at molecular response 4.5(MR 4.5).13 cases(26%)was in undetetable minimal residual diease(UMRD).21 cases(42%)did not reach the molecular reaction,including 15 cases of complete hematologic response(CHR),and 6 cases of no hematologic reaction.5 cases(10%)failed to detect the gene or blood routine and the curative effect is unknown.1 case did not follow-up after discontinuation in 7 patients,who reach MMR at the time of withdrawal of TKI.And,among 3 patients of withdrawal of MR4.0,1 case failed to follow-up after discontinuation,so after stoping TKI treatment,there was 22 patients with molecular response and definite curative efficacy in all.2.In 22 cases of molecular response of withdrawal patients,there were 18 males(81.8%)and 4 females(18.2%).The median time of follow-up was 33 months(range 4 months to 68 months).After discontinuation of TKI,8 cases didnot relapse(36.4%,8/22),and 14 cases relapsed(64.6%,14/22).The patients of recurrence cases were all molecular relapse.The median time to recurrence was 8 months(range 3 months to 48 months),and most patients relapsed within 6 months after discontinuation of TKI.On the reasons for withdrawal,5 cases of economic reasons,16 cases of molecular response,1 cases of pregnancy.The median duration of TKI treatment was 30 months(range 12 months to 72 months).The median time of treatment to molecular response was 7 months(range 3 months to 15 months).The median time of maintaining molecular response was 24 months(range 1 months to 60 months).The median time of withdrawal was 12.5 months(range 3 months to 67 months).3.In 22 patients who obtained molecular response before withdrawal,comparing the median duration of TKI therapy between 8 cases of non recurrence group and 14 cases of molecular relapse group,the difference was not statistically significant(P=0.089).Comparing the time to molecular MMR between non recurrence group and recurrence group,there was no statistically significant difference(P=0.318).Comparing age between no recurrence group and recurrence group,no statistically significant difference(P=0.473).Comparing gender between no recurrence group and molecular relapse group,no statistically significant difference(P=0.610).Sokal score was performed in 22 patients,comparing the recurrence rate in the three groups of low risk,inmediate risk and high risk,of which the difference was statistically significant(P=0.034),which indicated that patients with high risk of Sokal score would be more likly to relapse.Divided the group with the duration of molecular reaction in 22 patients,one group of higher than or equal to 24 months,one group of less than 24 months,comparing the efficacy between the two groups after withdrawal,the difference was statistically significant(P=0.018),which suggested that the group of higher than or equal to 24 months was less likly to relapse.4.To the end of follow-up,22 patients,of which obtained molecular response when discontinuated of TKI,were all survived.The median duration of TKI in 22 patients was 30 months(range 12 months to 72 months),And they had no disease progression after discontinuating(accelerated phase or acute transformation).And 5 year progression free survival was 43.6%.5.21 patients did not reach the molecular response when stopping TKI,and the median duration of TKI was 12 months(range 3 months to 44 months),in which 4 patients showed acute transformation after discontinuation,of which 3 cases died.and in which 3 cases went into accelerated phase after withdrawal.Conclusion The results in this study showed,the curative effect of the patients who discontinuated with molecular response is better than those who discontinuated without molecular response,36.4% patients with CML treated with TKI,who obtained molecular response(at least MMR)and the time maintained molecular response of at least 2 years,were able to discontinuate safely.The efficacy after drug withdrawal may be related to the Sokal score and the duration of molecular responses before drug withdrawal.