异基因造血干细胞移植治疗儿童侵袭性NK细胞白血病一例并文献复习

Allogeneic hematopoietic stem cell transplantation for children with aggressive natural killer cell leukemia:one case report with a literature review

目的探讨儿童侵袭性NK细胞白血病(aggressive natural killer cell leukemia,ANKL)的临床特征、治疗方案及预后。方法回顾性分析2019年6月郑州大学第一附属医院儿科收治的1例ANKL患儿的临床资料。同时以"侵袭性NK细胞白血病""儿童"和"aggressive natural killer cell leukemia""children"为中英文关键词,对中国知网、万方数据库、PubMed自建库至2021年12月的相关文献进行检索,探讨儿童ANKL的临床特征、治疗方案及预后。结果患儿,女,8岁,以发热为首发表现,伴面色苍黄、乏力、肝、脾、淋巴结肿大,三系血细胞减少等临床表现。经流式细胞术免疫表型分析、免疫组织化学染色等检查确诊为ANKL。给予化疗后桥接异基因造血干细胞移植(allo-geneic hematopoietic stem cell transplantation,allo-HSCT)。截至2022年4月,随访2年余,患儿处于无病生存状态。文献检索最终找到符合条件的中文文献7篇,英文文献10篇,共17例ANKL患儿。结合本组1例,18例患儿中首发表现为发热者15例,皮疹1例,会阴部包块1例,腹泻、呕吐等消化道症状1例。6例在发病早期被误诊。4例予单纯化疗,其中3例按急性淋巴细胞白血病化疗方案化疗,死亡1例;1例按"顺铂+长春新碱+多柔比星+异环磷酰胺"方案化疗后死亡。5例予化疗缓解后桥接allo-HSCT,1例在allo-HSCT术后9个月因多脏器功能衰竭而死亡。9例放弃治疗出院后死亡。结论ANKL病情进展快,临床表现多样,易误诊,预后差。对于疑似ANKL患者,建议临床医师进行多部位多次骨髓穿刺、尽早行流式细胞术免疫表型分析以明确诊断。目前allo-HSCT可能是ANKL患者获得长期生存的治疗手段。

Objective To summarize the clinical features,treatments and prognoses of aggressive natural killer cell leukemia(ANKL)in children.Methods Clinical data and follow-up results were retrospectively reviewed for one hospitalized case of ANKL in June 2019.Through a literature search,the relevant items were retrieved from the databases of China National Knowledge Infrastructure,WanFang and PubMed using the Chinese and English keywords of"aggressive natural killer cell leukemia"and"children"up to December 2021.Results This 8-year-old girl was diagnosed with ANKL by flow cytometric immunophenotype and immunohistochemical stain.Fever was the initial manifestation accompanied by sallow complexion,fatigue,enlargement of liver,spleen and lymph node and hematopenia of three lines.Allogeneic hematopoietic stem cell transplantation(allo-HSCT)was performed after chemotherapy.As of April 2022,the child stayed in a disease-free survival state after follow-ups for over 2 years.The literature search finally yielded 7 eligible Chinese and 10 English reports with a total of 17 pediatric ANKLs.In this group,there were fever(n=15),rash(n=1),perineal mass(n=1)and diarrhea,vomiting and other digestive tract symptoms(n=1).Six cases were misdiagnosed during an early stage of disease.4 cases received chemotherapy alone,3 cases received chemotherapy regimen for acute lymphoblastic leukemia,1 child died and one death occurred after received chemotherapy regimen of"cisplatin+vincristine+doxorubicin+ifosfamide".Allo-HSCT was performed in 5 patients after remission with chemotherapy and one child died from multiple organ failure at 9 months after allo-HSCT.Nine cases gave up treatment.Conclusions ANKL has a rapid disease progression,diverse clinical manifestations,easy misdiagnosis and poor prognosis.For suspected ANKL cases,clinicians perform multiple bone perforations at multiple sites and immunophenotype by flow cytometry as soon as possible to confirm the diagnosis.Currently allo-HSCT offers a long-term survival of ANKL patients.