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急性早幼粒细胞白血病成功治疗后发生的治疗相关髓系肿瘤:4例报告及文献复习

[Therapy-related myeloid neoplasms after successful treatment for acute promyelocytic leukemia: a report of four cases and literature review].

作者信息

Wang Z, Xu M Z, Chen Y F, Xue F, Zhang L, Hu Y M, Li C W, Li S Z, Wang J X, Mi Y C

机构信息

State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Instituteof Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.

出版信息

Zhonghua Xue Ye Xue Za Zhi. 2019 Dec 14;40(12):1008-1014. doi: 10.3760/cma.j.issn.0253-2727.2019.12.007.

Abstract

To investigate the clinical characteristics, diagnosis, treatment and prognosis of therapy-related myeloid neoplasms (t-MNs) after successful treatment for acute promyelocytic leukemia (APL) . 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. 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. 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, t-MNs should be considered as a differential diagnosis.

摘要

探讨急性早幼粒细胞白血病(APL)成功治疗后治疗相关髓系肿瘤(t-MNs)的临床特征、诊断、治疗及预后。回顾性收集2012年10月至2019年1月在中国医学科学院血液病医院诊断为继发于APL的t-MNs的4例患者的临床资料。复习t-MNs相关文献。4例均为女性,诊断APL时中位年龄42岁(范围40 - 53岁)。诱导和巩固方案方面,3例患者接受全反式维甲酸(ATRA)、三氧化二砷(ATO)联合蒽环类/蒽醌类和/或阿糖胞苷治疗。1例患者仅接受ATRA及其他辅助药物治疗,未使用烷化剂。4例患者在APL完全缓解(CR)后40至43个月发生t-MNs,其中1例为治疗相关骨髓增生异常综合征(t-MDS),3例为急性髓系白血病(t-AML)。发生t-MNs时PML-RARα融合基因均为阴性。3例t-AML患者接受3至4次再诱导方案治疗,其中1例在完全缓解(CR)后接受了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药物治疗。中位随访54.5(48 - 62)个月后,2例t-AML患者死亡,t-MN后的中位总生存期为12(5 - 18)个月。1989年至,2018年,文献共报道63例t-MN病例。加上本中心4例患者后共分析67例,其中男性27例,女性40例,中位年龄52.5(15 - 76)岁。中位潜伏期为39(12 - 126)个月,t-MN诊断后的中位总生存期为10(1 - 39)个月。虽然罕见,但t-MNs可能在APL成功控制后发生。目前尚无t-MNs的防治指南,其预后很差。如果APL 3年后出现血细胞减少或外周血细胞其他异常,应考虑t-MNs进行鉴别诊断。

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