|Table of Contents|

Clinical efficacy and safety of tyrosine kinase inhibitors combined with chemotherapy in treatment of acute myelogenous leukemia-M2b with C-KIT mutation

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2021 02
Page:
298-302
Research Field:
Publishing date:

Info

Title:
Clinical efficacy and safety of tyrosine kinase inhibitors combined with chemotherapy in treatment of acute myelogenous leukemia-M2b with C-KIT mutation
Author(s):
MI Ruihua1; CHEN Lin1; GUO Zhen2; LIU Sha1; YU Ping1; ZHU Songtao1; YUAN Fangfang1; YIN Qingsong1; WEI Xudong1
1.Department of Hematopathy;2.Central Laboratory,the Affiliated Cancer Hospital of Zhengzhou University,Henan Zhengzhou 450008,China.
Keywords:
acute myelogenous leukemia; t(8; 21); gene; C-KIT muation; TKI
PACS:
R733.71
DOI:
10.3969/j.issn.1672-4992.2021.02.025
Abstract:
Objective:To analyze the efficacy and safety of tyrosine kinase inhibitors(TKI) combined with chemotherapy in treatment of acute myelogenous leukemia-M2b(AML-M2b) with C-KIT mutation.Methods:Ten patients of AML-M2b with C-KIT mutation were in hospital from February 2016 to June 2019,aged from 14～59 years old including 5 cases of males and 5 cases of females.Ten patients were including 1 patient who relapsed after many cycles of chemotherapy,2 patients who did not remission after many cycles of chemotherapy,3 patients who did not remission after one cycle of chemotherapy,2 patients whose fusion gene was not negative after many cycles of chemotherapy,2 patients whose fusion gene turned to be positive after many cycles of chemotherapy.Then 10 patients who were treated with tyrosine kinase inhibitors (2 patinets with imatinib,8 patients with dasatinib) combined with chemotherapy respectively were reinduced,and we would evaluate the efficacy and monitor the adverse reaction.Results:There were 2 patients (2/10,20%)whose mutation site of C-KIT was in exon 8,8 patients(8/10,80%) in exon 17.Two patients were in vain after combination therapy,and the total effective rate was 80%.There were no liver and kidney dysfunction and pleural effusion during the whole time of treatment.Two patients accepted allo-HSCT,one of them died in the allo-HSCT,the other one relapsed three months later.The over survival of the remaining 8 patients after TKI treatment was 4 months+～30 months+.Conclusion:The main mutation site of C-KIT in AML-M2b was D816 mutation,Adding TKI to treatment in AML-M2b with C-KIT mutation could improve the outcome obviously.

References:

［1］MROZEK K,HEEREMA NA,BLOOMFIELD C.Cytogenetics in acute leukemia［J］.Blood Rev,2004,18(2):115-136.
［2］ NCCN.NCCN Clinical Practice Guidelines in Oncology(NCCN Guidelines) Acute myeloid Leukemia(Version3.2019-May 7,2019)［S］.
［3］ 成人急性髓系白血病（非急性早幼粒细胞白血病）中国诊疗指南（2017 年版）［J］.中华血液学杂志,2017,38(3):177-182.Chinese guidelines for diagnosis and treatment of adult acute myeloid leukemia(not APL)(2017)［J］.Chin J Hematol,2017,38(3):177-182.
［4］ RUBNITZ JE,RAIMONDI SC,HALBERT AR,et al.Characteristics and outcome of t(8;21)-positive childhood acute myeloid leukemia:A single institution’s experience［J］.Leukemia,2002,16(10):2072-2077.
［5］ SCHLENK RF,BENNER A,KRAUTRE J,et al.Individual patient data-based meta-analysis of patients aged 16 to 60 years with core binding factor acute myeloid leukemia:A survey of the German Acute Myeloid Leukemia Intergroup［J］.J Clin Oncol,2004,22(18):3741-3750.
［6］ NGUYEN S,LEBLANC T,FENAUX P,et al.A white blood cell index as the main prognostic factor in t(8;21) actue myeloid leukemia(AML):A survey of 161 cases from the Ffench AML Intergroup［J］.Blood,2002,99(10):3517-3523.
［7］WANG YY,ZHOU GB,YIN T,et al.AML1-ETO and C-KIT mutation over-expression in t(8;21) leukemia:Implication in stepwise leukemogenesis and response to Gleevc［J］.PNAS,2005,102(4):1104-1109.
［8］ PASCHKA P,MARCUCCI G,RUPPERT AS,et al.Adverse prognostic signification of KIT mutations in adute acute myeloid leukemia with inv(16) and t(8;21):A cancer and leukemia group B study［J］.J Clin Oncol,2006,24(24):3904-3911.
［9］ CAIROLI R,BEGHINI A,GRILLO G,et al.Prognostic impact of c-KIT mutations in core binding factor leukemia:an Italian retrospective study［J］.Blood,2006,107(9):3463-3468.
［10］沈悌,赵永强.血液病诊断及疗效标准［M］.北京:科学出版社,2018:97-110.SHEN T,ZHAO YQ.Criteria for diagnosis and treatment of hematological diseases［M］.Beijing:Science Press,2018:97-110.
［11］ MARCUCCI G,MROZEK K,RUPPERT AS,et al.Prognostic factors and outcome of core binding factor acute myeloid leukemia with t(8;21) differ from those of patients with inv(16):A cancer and leukemia group B study［J］.J Clin Oncol,2005,23(24):5705-5717.
［12］ 乔曼,李渭阳,孙爱宁,等.核心结合因子相关性急性髓系白血病中酪氨酸激酶突变分析及其临床意义［J］.中华血液学杂志,2011,32(10):679-683.QIAO M,LI WY,SUN AN,et al.Analysis of tyrosine kinases gene mutations in core binding factor related acute myeloid leukemia and its clinical significance［J］.Chin J Hematol,2011,32(10):679-683.
［13］ NANRI T,MATSUNO N,KAWAKITA T,et al.Imatinib mesylate for refractory acute myeloblastic leukemia harboring inv(16) and a C-KIT exon 8 mutation［J］.Leukemia,2005,19(9):1673-1675.
［14］ CORBIN AS,DEMEHRI S,GRISWO1D IJ,et al.In vitro and in vivo activity of AIP-based kinase inhibitor AP23464 and AP23848 against activation-loop mutants of Kit［J］.Blood,2005,106(1):227-234.
［15］GROWNEY JD,CLARK JJ,ADELSPERGER J,et al.Activation mutations of human c-KIT resistant to imatinib mesylate are sensitive to the tyrosine kinase inhibitor PKC412［J］.Blood,2005,106(2):721-724．
［16］ SHAH NP,LEE FY,LUO R,et al.Dasatinib(BMS-354825)inhibits KITD816V,an imatinib-resistant activating mutation that triggers neoplastic growth in most patients with systemic mastocytosis［J］.Blood,2006,l08(1):286-291．
［17］ PASCHKA P,SCHLENK RF,WEBER D,et al.Adding dasatinib to intensive treatment in core-binding factor acute myeloid leukemia-results of the AMLSG 11-08 trial［J］.Leukemia,2018,32(7):1621-1630.
［18］ CIOCCIO J,CLAXTON D.Therapy of acute myeloid leukemia:therapeutic targeting of tyrosine kinases［J］.Expert Opin Investig Drugs,2019,28(4):337-349.

Memo

Memo:
河南省医学科技攻关计划省部共建项目（编号：201701027）;河南省科技厅科技攻关项目（编号：202102310365）
Last Update: 1900-01-01