吉瑞替尼靶向治疗伴FLT3突变急性髓系白血病5例并文献复习

Geritinib in the targeted therapy of acute myeloid leukemia with FLT3 mutation:report of 5 cases and review of literature

目的:探讨吉瑞替尼治疗伴FLT3突变急性髓系白血病(AML)患者的效果及安全性。方法:回顾性分析2020年3月至2021年4月在香港大学深圳医院、深圳市人民医院、深圳市第二人民医院、深圳大学总医院确诊并选择吉瑞替尼治疗的5例伴FLT3突变AML患者资料。患者选择吉瑞替尼联合两药或三药治疗;用药期间,每周查血常规,每2周查肝功能及肾功能,每1~3个月复查骨髓穿刺,了解骨髓形态学、微小残留病(MRD)及FLT3突变表达水平。分析使用吉瑞替尼后疗效及不良反应发生情况,评估生存情况。结果:5例患者初诊时均白细胞数增多,其中FLT3-内部串联重复(ITD)突变3例,FLT3-酪氨酸激酶结构域(TKD)突变2例。5例中,1例非复发难治,造血干细胞移植+60天开始口服吉瑞替尼维持治疗。4例复发难治患者中,1例妊娠期女性终止妊娠后移植,后复发,口服吉瑞替尼后获得完全缓解(CR)并一直使用吉瑞替尼维持治疗;1例16岁儿童应用吉瑞替尼后接近CR;1例应用吉瑞替尼等获CR后行亲缘半相合移植,吉瑞替尼维持治疗;1例复发后应用吉瑞替尼等达CR。移植后使用吉瑞替尼维持治疗的3例患者均未复发。使用吉瑞替尼的主要不良反应包括贫血、中性粒细胞减少、皮疹及氨基转移酶升高等。5例患者中位随访15个月(6~20个月),至2021年11月末次随访,患者均生存,其中4例无病生存。结论:吉瑞替尼治疗可使伴FLT3突变复发难治AML患者达到CR,为患者移植争取机会。移植后吉瑞替尼维持治疗可降低复发风险、提高生存率。暂未观察到吉瑞替尼严重不良反应。

Objective:To investigate the efficacy and safety of geritinib in the treatment of acute myeloid leukemia (AML) with FLT3 mutation.Methods:The clinical data of 5 AML patients with FLT3 mutation who were diagnosed in the University of Hong Kong-Shenzhen Hospital, Shenzhen People's Hospital, Shenzhen Second People's Hospital, Shenzhen University General Hospital from March 2020 to April 2021 were retrospectively analyzed. Relapsed patients concurrently received two- or three-drug chemotherapy combined with geritinib. Blood routine was checked once a week;liver function and renal function were checked once every 2 weeks during treatment. Bone marrow puncture was performed once every 1 to 3 months to monitor the bone marrow morphology, minimal residual disease (MRD) and FLT3 mutation expression levels. The efficacy, side effects, overall survival of these patients were analyzed after treatment with geritinib.Results:The white blood cell was increased in all the 5 patients at the initial diagnosis. FLT3 mutations analysis showed FLT3-internal tandem duplication (ITD) (3 cases) and FLT-3 tyrosine-kinase domain (TKD) (2 cases). Among 5 patients, 1 patient was relapse-free with maintenance therapy of oral geritinib after hematological stem cell transplantation (HSCT) for 60 days;among other 4 relapsed and refractory patients, 1 female patient after pregnancy relapsed after transplantation and then achieved complete remission followed by the maintenance therapy with geritinib after oral geritinib, 1 16-year-old patient achieved treatment outcome close to the complete remission after treatment with geritinib, 1 patient achieved complete remission after treatment with geritinib, and then underwent haplo-HSCT followed by the maintenance therapy with geritinib and the other 1 relapsed patient achieved complete remission after treatment with geritinib. After transplantation, 3 patients receiving maintenance treatment of geritinib did not relapse. The main side effects included anemia, decreased neutrophil count, rash, and increased aminotransferase. The median follow-up time of 5 patients was 15 months (6-20 months). All 5 cases survived until the last follow-up in November 2021 and 4 patients were disease-free.Conclusions:Relapsed and refractory AML patients with FLT3 mutation can achieve complete remission after treatment with geritinib and get a chance for transplantation. Geritinib may reduce the risk of recurrence after transplantation and improve survival rate. No serious side effects occur in geritinib treatment.