噬血细胞综合征治疗后继发急性白血病2例报告并文献复习

Therapy-related acute leukemia after treatment for hemophagocytic lymphohistiocytosis: a report of 2 cases and literature review

目的探讨噬血细胞综合征(HLH)治疗后继发急性白血病的临床特征及预后。方法收集2例EB病毒相关HLH(EBV-HLH)患儿在接受化疗后继发急性白血病的临床资料,并复习相关文献。结果2例患儿均为男性,分别为4岁、7岁,均接受HLH-2004方案化疗,依托泊苷(VP16)的累积量分别为1500mg/m^2及3900mg/m^2;例1于首次化疗18个月后继发急性早幼粒细胞白血病(M3),予维甲酸加柔红霉素诱导化疗后达完全缓解(CR),此后规则化疗,随访30个月,持续CR;例2于首次化疗50个月后继发急性单核细胞白血病(M5),予化疗后达CR,但于诊断急性白血病15个月后复发,继予造血干细胞移植后再次达CR,此后随访1年,持续CR。2例患儿加文献报道13例HLH接受化疗后继发急性白2血病患儿,共15例患儿,男10例、女5例,中位年龄2岁6个月(4个月~19岁),VP16的累积剂量中位数3900mg/m(400~20975mg/m^2),HLH与继发白血病的间隔中位时间24个月(6~72个月)。15例患儿中,5例M3,只接受化疗,均无病存活;10例其他类型急性白血病,3例接受化疗(1例死亡、2例不明),6例造血干细胞移植(3例存活、3例死亡);1例放弃治疗。结论HLH治疗后继发的急性白血病多为急性髓系白血病,其中急性早幼粒细胞白血病接受维甲酸为基础的联合化疗,预后良好;而其他类型急性白血病预后差,造血干细胞移植或可改善预后。

Objective To investigate the clinical characteristics and prognosis of acute leukemia after treatment for hemophagocytic lymphohistiocytosis (HLH). Methods Clinical data of two cases with acquired EBV-triggered HLH with progression to acute leukemia following chemotherapy was analyzed, and 13 cases of secondary acute leukemia (sAL) following the treatment of HLH in the literature were reviewed. Results Two male cases with acquired EBV-triggered HLH (EBV-HLH) were treated with HLH-2004 regimen. The cumulative dose of etoposide was 1500 mg/m2 and 3900 mg/m2, respectively. One child developed acute promyelocytic leukemia (APL) 18 months after the first chemotherapy regimen, and achieved complete remission (CR) after induction chemotherapy with retinoic acid and daunorubicin. Then he received regular chemotherapy, and continued CR was observed after following up for 30 months. Another patient developed acute mononuclear leukemia (M5) 50 months after the first chemotherapy, who reached CR after AML chemotherapy. However, he relapsed 9 months after withdrawal and reached CR after hematopoietic stem cell transplantation. Following up for 12 months, the patient got continued CR. Thirteen cases of sAL following chemotherapy for HLH were reported. Of the 15 cases, 10 were male and 5 were female. The median age was 2 years and 6 months old (4 months to 19 years old). The cumulative dose of VP16 was 3900 mg/m2 (400-20975). The median interval between HLH and secondary leukemia was 24 months (6-72). The types of secondary leukemia included M3 in 5 cases who received chemotherapy and survived without disease, and other types of AL in 10 cases, in which 3 cases received chemotherapy (1 case died and 2 cases were unknown), 6 cases were performed hematopoietic stem cell transplantation ( 3 cases survived and 3 cases died), and 1 case gave up treatment after suffering from AL. Conclusions Most of the acute leukemia secondary to HLH are AML. APL has a good prognosis treated with retinoic acid-based combination chemotherapy, while other types have a poor prognosis. Hematopoietic stem cell transplantation may improve the prognosis.