慢性髓细胞性白血病患儿酪氨酸激酶抑制剂停药的研究进展

Research progress on tyrosine kinase inhibitors discontinuation in children with chronic myeloid leukemia

慢性髓细胞白血病(CML)是一种造血干细胞异常克隆性疾病,酪氨酸激酶抑制剂(TKI)为CML的一线治疗药物。近年,TKI停药研究已在CML成年患者中广泛开展,并取得一定成效,在获得深度和持续分子学反应(MR)的CML成年患者中,40%~60%患者TKI停药成功。目前CML患儿TKI停药临床研究较少且研究队列较小。几项队列研究结果显示,对MR4.0(BCR-ABLIS≤0.01%)维持时间≥2年的CML患儿,可以尝试停用TKI,并且CML患儿的无治疗缓解(TFR)率与CML成年患者停药研究的文献报道结果接近。笔者拟就CML患儿在达到停药标准后达到TFR的可能性、停药后分子学复发的监测与再治疗、停药对患儿的影响及TKI停药前间歇给药等对CML患儿TKI停药的研究进展进行综述,以期为CML患儿TKI停药临床实践提供参考,促进更多患儿成功达到TFR。

Chronic myeloid leukemia(CML)is a clonal disorder of abnormal hematopoietic stem cell,with tyrosine kinase inhibitor(TKI)as the first-line therapy.In recent years,studies on TKI discontinuation research have been widely carried out in adult with CML and achieved excellent results.40%-60%of adult patients with deep and sustained molecular response(MR)to TKI treatment can successfully discontinue TKI.There are few studies on TKI discontinuation in children with CML and the study cohorts are small.Several cohort studies have shown that children with CML who maintain MR4.0(BCR-ABLIS≤0.01%)for at least 2 years can try to discontinue TKI.The present study indicated that the probability of treatment-free remission(TFR)rate in children with CML is similar to the results reported in cohorts of adults.This article intends to review the research progress of TKI discontinuation in children with CML in terms of possibility of reaching TFR after reaching the criteria of discontinuation,the monitoring of molecular relapse after discontinuation and re-treatment after relapse,the influence of TKI discontinuation on pediatric patients and effects of intermittent TKI treatment before discontinuation,to provide proposals for clinical practice of TKI discontinuation in children with CML and promote more children to successfully achieve TFR.