摘要目的 探讨急性早幼粒细胞白血病(APL)患者继发治疗相关性髓系肿瘤(t-MN)的临床特点、诊断、治疗及预后.方法 回顾性分析中国医学科学院血液病医院2012年10月至2019年1月收治的4例APL继发t-MN患者的临床资料,并进行相关文献复习.结果 4例APL继发t-MN患者均为女性,中位年龄42(40～53)岁,3例接受了以维甲酸(ATRA)+亚砷酸(ATO)为基础联合蒽环/蒽醌类药物±阿糖胞苷的前期诱导缓解及巩固治疗方案,1例采用了ATRA联合蒽环/蒽醌类药物±阿糖胞苷的治疗方案,均没有使用烷化剂.在APL获得完全缓解(CR)后40～ 43个月出现t-MN,其中治疗相关性骨髓增生异常综合征(t-MDS)1例,治疗相关性急性髓系白血病(t-AML)3例,出现t-MN时PML-RARα融合基因均为阴性.3例t-AML患者接受了2～4个疗程再诱导治疗,其中有1例t-AML患者在获得CR后行异基因造血干细胞移植(allo-HSCT),1例t-MDS患者接受了去甲基化治疗.中位随访54.5(48 ～62)个月,2例t-AML患者死亡,出现t-MN后中位生存期为12(5～ 18)个月.1989至2018年文献共报道63例APL继发t-MN病例,与本次报道的4例汇总分析,67例患者中男27例,女40例;中位年龄为52.5(15～76)岁;中位潜伏期39(12～168)个月,确诊t-MN后中位生存时间为10(1～39)个月.结论 APL继发t-MN较为少见,目前缺乏有效的防治措施,预后不佳,在随访过程中(尤其是获得CR后39个月左右)若出现病情变化,应警惕t-MN的发生,对此类患者应尽快明确疾病的变化,给予合理的治疗.

abstractsObjective To investigate the clinical characteristics,diagnosis,treatment and prognosis of therapy-related myeloid neoplasms(t-MNs) after successful treatment for acute promyelocytic leukemia (APL).Methods Clinical data of 4 patients,diagnosed as t-MNs secondary to APL at Hematology Hospital of Chinese Academy of Medical Sciences from October 2012 to January 2019,were collected retrospectively.T-MNs related literature was reviewed.Results The 4 cases were all females,with the median age 42 (range 40-53) years old at the diagnosis of APL.Regarding the induction and consolidation regimens,3 patients received all-trans retinoid acid (ATRA) and arsenic trioxide (ATO) combined with anthracycline/anthraquinone and/or cytosine.One patient only received ATRA and other auxiliary drugs.Alkylating agents were not administrated.The 4 patients developed t-MNs 40 to 43 months after complete remission (CR) of APL,including 1 case of therapy-related myelodysplastic syndrome (t-MDS) and 3 cases of acute myeloid leukemia (t-AML).The PML-RARα fusion genes were all negative when t-MNs developed.The three patients with t-AML were treated with 3 to 4 re-induction regimens,one of whom underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) after complete remission (CR).One patient with t-MDS received hypomethylating agents.After a median follow-up of 54.5 (48-62) months,2 patients with t-AML died,the median overall survival after t-MN was 12 (5-18) months.From 1989 to 2018,a total of 63 t-MN cases were reported in the literature.Therefore,67 cases were analyzed when four patients in our center were added,including 27 males and 40 females with median age 52.5 (15-76) years.The median latency was 39 (12-126) months and the median overall survival after diagnosis of t-MN was 10 (1-39) months.Conclusions Although rare,t-MNs may occur after successful control of APL.There are no existing guidelines for prevention and treatment of t-MNs,which have very poor prognosis.If cytopenia or other abnormalities of peripheral blood cells develop after 3 years of APL,tMNs should be considered as a differential diagnosis.