[Analysis of 7 cases of pediatric acute myeloid leukemia with DEK-NUP214 fusion gene].

Objective: To investigate the clinical features, treatment regime, and outcome of pediatric acute myeloid leukemia (AML) with DEK-NUP214 fusion gene. Methods: The clinical data, genetic and molecular results, treatment process and survival status of 7 cases of DEK-NUP214 fusion gene positive AML children admitted to the Pediatric Blood Diseases Center of Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences from May 2015 to February 2022 were analyzed retrospectively. Results: DEK-NUP214 fusion gene positive AML accounted for 1.02% (7/683) of pediatric AML diagnosed in the same period, with 4 males and 3 females. The age of disease onset was 8.2 (7.5, 9.5) years. The blast percentage in bone marrow was 0.275 (0.225, 0.480), and 6 cases were M5 by FAB classification. Pathological hematopoiesis was observed in all cases except for one whose bone marrow morphology was unknown. Three cases carried FLT3-ITD mutations, 4 cases carried NRAS mutations, and 2 cases carried KRAS mutations. After diagnosis, 4 cases received IAE induction regimen (idarubicin, cytarabine and etoposide), 1 case received MAE induction regimen (mitoxantrone, cytarabine and etoposide), 1 case received DAH induction regimen (daunorubicin, cytarabine and homoharringtonine) and 1 case received DAE induction regimen (daunorubicin, cytarabine and etoposide). Complete remission was achieved in 3 cases after one course of induction. Four cases who did not achieved complete remission received CAG (aclarubicin, cytarabine and granulocyte colony-stimulating factor), IAH (idarubicin, cytarabine and homoharringtonine), CAG combined with cladribine, and HAG (homoharringtonine, cytarabine and granulocyte colony-stimulating factor) combined with cladribine reinduction therapy, respectively, all 4 cases reached complete remission. Six patients received hematopoietic stem cell transplantation (HSCT) after 1-2 sessions of intensive consolidation treatment, except that one case was lost to follow-up after complete remission. The time from diagnosis to HSCT was 143 (121, 174) days. Before HSCT, one case was positive for flow cytometry minimal residual disease and 3 cases were positive for DEK-NUP214 fusion gene. Three cases accepted haploid donors, 2 cases accepted unrelated cord blood donors, and 1 case accepted matched sibling donor. The follow-up time was 20.4 (12.9, 53.1) months, the overall survival and event free survival rates were all 100%. Conclusions: Pediatric AML with DEK-NUP214 fusion gene is a unique and rare subtype, often diagnosed in relatively older children. The disease is characterized with a low blast percentage in bone marrow, significant pathological hematopoiesis and a high mutation rate in FLT3-ITD and RAS genes. Low remission rate by chemotherapy only and very high recurrence rate indicate its high malignancy and poor prognosis. Early HSCT after the first complete remission can improve its prognosis.目的： 探讨DEK-NUP214融合基因阳性儿童急性髓系白血病（AML）的临床特征、治疗方案和预后。 方法： 回顾性分析2015年5月至2022年2月中国医学科学院血液病医院儿童血液病诊疗中心收治的7例DEK-NUP214融合基因阳性AML患儿临床特征、遗传和分子学结果、治疗和生存情况。 结果： DEK-NUP214融合基因阳性的AML占同期诊断AML的1.02%（7/683）。7例患儿中男4例、女3例，发病年龄8.2（7.5，9.5）岁。骨髓原始细胞比例为0.275（0.225，0.480），6例FAB分型为M5，除1例不详外余均伴病态造血。3例携带FLT3-ITD基因突变，4例携带NRAS基因突变，2例携带KRAS基因突变。诊断后诱导方案为：4例IAE（伊达比星+阿糖胞苷+依托泊苷），1例MAE（米托蒽醌+阿糖胞苷+依托泊苷），1例DAH（柔红霉素+阿糖胞苷+高三尖杉酯碱），1例DAE（柔红霉素+阿糖胞苷+依托泊苷）。1个疗程诱导达完全缓解者3例。4例患儿未缓解，分别接受CAG（阿克拉霉素+阿糖胞苷+粒细胞集落刺激因子），IAH（伊达比星+阿糖胞苷+高三尖杉酯碱），CAG联合克拉屈滨和HAG（高三尖杉酯碱+阿糖胞苷+粒细胞集落刺激因子）联合克拉屈滨再诱导治疗，均达完全缓解。1例患儿缓解后失访，余6例患儿巩固强化治疗1~2个疗程后进行造血干细胞移植（HSCT）。从确诊至HSCT的时间为143（121，174）d。移植前流式微小残留病阳性者1例，DEK-NUP214融合基因阳性者3例。3例为单倍体供者，2例无关脐血供者，1例为同胞全相合供者。6例患儿随访20.4（12.9，53.1）个月，总生存率和无事件生存率均为100%。 结论： DEK-NUP214融合基因阳性的儿童AML发病率极低，发病年龄偏大，骨髓原始细胞比例偏低，伴病态造血，常伴FLT3-ITD及RAS基因突变；此类型AML恶性度高，化疗缓解率低，复发率极高，首次缓解后尽早移植可改善预后。.