Objective: 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, t-MNs should be considered as a differential diagnosis.
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。.
Keywords: Leukemia, promyelocytic, acute; Myeloid neoplasm, therapy-related; Treatment efficacy.