异基因造血干细胞移植联合地西他滨维持治疗成功救治范可尼贫血进展为急性髓系白血病1例报告

doi:10.12372/jcp.2024.22e1673

摘要/Abstract

摘要：

目的探讨异基因造血干细胞移植（allo-HSCT）后序贯地西他滨用于治疗范可尼贫血（FA）进展为急性髓系白血病（AML）患儿的可行性及有效性。方法回顾分析1例FA进展为AML患儿接受同胞弟弟作为供体的单倍体移植，移植后予地西他滨维持治疗。结果患儿生后6岁出现贫血，8岁确诊范可尼贫血，按照再生障碍性贫血治疗（环孢素、安雄）6年无效，且进行性三系下降，血小板无效输注，骨髓检查诊断为AML。骨髓二代基因测序检测，仍然表现为FANCA基因c.3348+1G>A纯合变异。遂予FLAG方案（氟达拉滨+阿糖胞苷+粒细胞集落刺激因子）化疗后桥接以TBI为基础的清髓性预处理方案，+15天粒细胞及血小板植入，移植后给予患者减量环孢素，保持Ⅱ度皮排排异直至移植后1年，移植后6个月开始予每2个月予地西他滨，共计6次，同时监测WT1的表达水平。现已经移植后近6年，患儿无事件生存中。结论 allo-HSCT后联合地西他滨序贯治疗能够有效治疗FA进展为AML。

关键词: 范可尼贫血, 急性髓系白血病, 造血干细胞移植, 地西他滨, 儿童

Abstract:

Objective To investigate the feasibility and effectiveness of sequential decitabine after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of children with Fanconi anemia (FA) progressing to acute myeloid leukemia (AML). Methods The clinical data of an 8-year-old girl with progression from FA to AML who received haploid transplantation (younger brother as donor) followed by decitabine maintenance therapy were retrospectively analyzed. Results The child presented with anemia at 6 years old and Fanconi anemia was diagnosed at 8 years old. The child was treated with cyclosporine and testosterone undecanoate for 6 years without response, presenting with progressive trilineage decline and ineffective platelet transfusions, and finally was diagnosed with AML by bone marrow examination. The results of bone marrow NGS test showed c.3348+1G>A homozygous variation in FANCA gene. The patient was treated with FLAG (fludarabine+cytarabine+granulocyte colony-stimulating factor) chemotherapy followed by a myeloablative preconditioning regimen based on whole body irradiation. Granulocyte and platelet were engrafted 15 days after transplantation. After transplantation, the child was given a reduced dose of cyclosporine and she maintained grade Ⅱ skin graft-versus-host disease until 1 year after transplantation. From 6 months after transplantation, decitabine was administered every 2 months for a total of 6 times, and the expression level of WT1 was monitored. It has now been nearly 6 years since the transplantation, and the child is in event-free survival. Conclusions The allo-HSCT combined with decitabine sequential therapy is effective in the treatment of AML progression from FA.

Key words: Fanconi anemia, acute myeloid leukemia, hematopoietic stem cell transplantation, dicitabine, child

戴银亮, 何海龙, 范丽艳, 李捷, 卢俊, 肖佩芳, 凌婧, 郑佳佳, 杜智卓, 胡绍燕. 异基因造血干细胞移植联合地西他滨维持治疗成功救治范可尼贫血进展为急性髓系白血病1例报告[J]. 临床儿科杂志, 2024, 42(1): 75-79.

DAI Yinliang, HE Hailong, FAN Liyan, LI Jie, LU Jun, XIAO Peifang, LING Jing, ZHENG Jiajia, DU Zhizhuo, HU Shaoyan. Successful rescue of progression from Fanconi anemia to acute myeloid leukemia by allogeneic hematopoietic stem cell transplantation with decitabine maintenance: a case report[J]. Journal of Clinical Pediatrics, 2024, 42(1): 75-79.

图/表 1

表1

患者病程时间轴"

时间	临床变现及检查/治疗情况
确诊FA前2年	血小板减少
确诊FA（8岁）	贫血、皮肤瘀斑瘀点体格检查：贫血貌，小眼裂，心肺正常，肝脾不大，全身散在咖啡牛奶斑及陈旧性出血点既往史：生后有六指切除术、十二指肠膜疝术病史血常规：WBC 5.4×10⁹/L，NE3.54×10⁹/L，HGB 70g/L，MCV 108fl，PLT 30×10⁹/L，Ret% 0.08% 外周血染色体脆性试验：阳性，断裂率7.39% 溶血全套：血红蛋白F 31.1% 骨髓穿刺涂片：骨髓有核细胞增生活跃低水平，G:E=0.5:1；全片巨核细胞见1只染色体：正常核型；FISH：46，XX，100% 骨髓衰竭基因：FANCA基因c.3348+1G>A纯合变异，行患者亲代验证：母亲FANCA基因c.3348+1G>A杂合变异诊断：FA，按照再生障碍性贫血予环孢素、安雄等治疗
确诊FA后6年	三系进行性下降，血小板无效输注查骨髓穿刺涂片：骨髓有核细胞增生活跃，G:E=2.4:1，髓系增生活跃，红系增生减低，淋巴细胞增生，全片巨核细胞少见，血小板簇状可及，原始细胞占25% 骨髓流式细胞术白血病免疫分型：分析幼稚群体占有核细胞16.8%，MPO 49.8%，CD33 84.6%，CD13 57.8%， CD11b 38.9%，CD64 48.2%，CD36 44.7%，CD15 41.1%，CD117 30.1%，CD34 84.9%，髓系表达；骨髓染色体为46，XX 骨髓衰竭基因：FANCA基因c.3348+1G>A纯合变异 43种白血病融合基因多重RT-PCR：未检出诊断：AML（FA转化）
MDS/AML治疗	“FLAG”方案化疗
21天后病情评估 allo-HSCT	复查骨髓及外周血象，达到CRi 胞弟HLA6/10单倍体移植，回输胞弟外周血干细胞的CD34⁺为3.68×10⁶/kg，非粒细胞为8.62×10⁸/kg
回输后15天	粒细胞及血小板植入
回输后6个月	监测WT1表达水平，呈进行性上升，每2月地西他滨，共计6次，WTI相对表达量呈进行性下降
回输后6年	上大学中

表1

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