成年人疑似原发性噬血细胞综合征合并侵袭性自然杀伤细胞白血病一例并文献复习

Adult suspected primary hemophagocytic syndrome complicated with aggressive natural killer cell leukemia:report of one case and review of literature

目的提高对成年人原发性噬血细胞综合征(HPS)合并侵袭性自然杀伤细胞白血病(ANKL)的认识。方法回顾性分析南方医科大学南方医院惠桥医疗中心2017年10月收治的1例疑似原发性HPS合并ANKL成年病例的临床资料,并复习国内外相关文献。结果患者,男性,21岁,持续发热,血细胞减少,脾大,纤维蛋白原低,铁蛋白显著升高,骨髓存在噬血细胞,自然杀伤(NK)细胞活性减低,可溶性CD25升高,流式细胞术检测NK细胞表达异常,存在家族性溶酶体转运调节因子(LYST)、UNC13D基因缺陷,疑似原发性HPS合并ANKL。给予4个疗程EPOCH+PEG-Asp(依托泊苷、地塞米松、长春地辛、环磷酰胺、多柔比星脂质体、培门冬酶)方案化疗,西达苯胺20 mg、2次/周维持治疗,无关全相合造血干细胞移植。随访35个月,疾病持续缓解。结论成年人HPS即使存在继发性病因,仍有必要行相关基因筛查以避免误诊。HPS合并ANKL患者病情进展迅速,早期病死率高,确诊后宜尽早采用EPOCH+PEG-Asp方案诱导治疗及异基因造血干细胞移植。

Objective To improve the understanding of adult primary hemophagocytic syndrome(HPS)with aggressive natural killer cell leukemia(ANKL).Methods The clinicopathological data of one adult patient with suspected primary HPS complicated with ANKL in Huiqiao Medical Center,Nanfang Hospital of Southern Medical University in October 2017 were retrospectively analyzed,and literatures were reviewed.Results A 21-year-old male patient presented with persistent fever,hemocytopenia,splenomegaly,low fibrinogen,a significant increase in ferritin,hemophagocytes in bone marrow,decreased natural killer(NK)cell activity,and increased soluble CD25.Flow cytometry detection showed that the expression of NK cells was abnormal,and there were familial lysosomal trafficking regulator(LYST)and UNC13D gene defects.He was suspected of primary HPS complicated with ANKL.The patient was given 4 courses of EPOCH+PEG-Asp(etoposide,dexamethasone,vindesine,cyclophosphamide,doxorubicin hydrochloride liposome,pegaspargase)regimen chemotherapy,20 mg of citalopidine twice a week maintenance therapy and matched unrelated hematopoietic stem cell transplantation.After 35 months of follow-up,he got sustained remission.Conclusions Even if there are secondary causes of adult HPS,it is necessary to screen out related genes to avoid misdiagnosis.HPS patients with ANKL progress rapidly,and the early mortality is high.EPOCH+PEG-Asp regimen induction therapy and allogeneic hematopoietic stem cell transplantation should be used as early as possible after diagnosis.