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摘要: 目的 总结分析成人早期前体T细胞急性淋巴细胞白血病(early T-cell precursor acute lymphoblastic leukemia，ETP-ALL)的临床特征、治疗效果及长期预后。方法 回顾性研究2020年4月至2023年12月诊治的15例ETP-ALL患者，分析基本临床特征、流式免疫分型、细胞遗传学及分子生物学异常、治疗方案与预后的关系。结果 成人急性T淋巴细胞白血病患者中ETP-ALL的发生率为21.8%，其中男性占73.3%，中位年龄43岁，中位骨髓原始细胞比例71.1%。髓系/干细胞抗原阳性表达CD34、CD117、HLA-DR、CD13、CD33等。22.2%的患者合并染色体异常，80.0%的患者合并分子生物学异常，常见的基因突变包括NOTCH1、PHF6、JAK3、ETV6、JAK1、WT1等。第1个疗程诱导缓解治疗后73.3%的患者达完全缓解，66.7%的患者达微小残留病阴性的完全缓解。中位随访时间15.4个月，1年及2年总生存率分别为90.9%和77.9%，1年及2年无复发生存率分别为86.2%和64.6%。结论 成人ETP-ALL同时具有淋系和髓系的临床特征，在VDCLP化疗方案的基础上联合应用髓系化疗药物或多种靶向药物或可提升完全缓解率，在第1次完全缓解期间尽快行异基因造血干细胞移植或可延长生存期。Abstract: Objective To summarize and analyze the clinical characteristics, treatment outcomes, and long-term prognosis of adult early T-cell precursor acute lymphoblastic leukemia(ETP-ALL).Methods A retrospective study was conducted on 15 ETP-ALL patients diagnosed and treated from April 2020 to December 2023. The relationships between basic clinical characteristics, immunophenotyping, cytogenetic and molecular biological abnormalities, treatment regimens, and prognosis were analyzed.Results The incidence of ETP-ALL among adult T-cell acute lymphoblastic leukemia patients was 21.8%, with 73.3% being male, a median age of 43 years, and a median percentage of bone marrow blast cells of 71.1%. Positive expressions of myeloid/stem cell antigens included CD34, CD117, HLA-DR, CD13, CD33, etc. 22.2% of patients had chromosomal abnormalities, and 80.0% of patients had molecular biology abnormalities, with common gene mutations including NOTCH1, PHF6, JAK3, ETV6, JAK1, WT1, etc. After the first course of induction therapy, 73.3% of patients achieved complete remission, and 66.7% achieved minimal residual disease negative complete remission. The median follow-up time was 15.4 months, with 1-year and 2-year overall survival rates of 90.9% and 77.9%, and 1-year and 2-year relapse-free survival rates of 86.2% and 64.6%, respectively.Conclusion Adult ETP-ALL presents with both lymphoid and myeloid characteristics. Adding myeloid chemotherapy drugs or multiple targeted therapies to the VDCLP regimen may improve complete remission rates, and performing allogeneic hematopoietic stem cell transplantation as soon as possible during the first complete remission period may prolong the survival.
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表 1 15例ETP-ALL患者的临床特征
患者编号 性别 年龄/岁 初治时原始细胞/% 分子生物学异常 总治疗线数 诱导缓解治疗线数 CR前诱导方案 第1个疗程反应 预后 1 男 33 71.10 否 4 1 VDLP MRD-CR 持续缓解 2 男 16 38.00 是 5 2 阿糖胞苷+甲强龙+西达本胺、VDLP 未缓解 C2后持续缓解 3 男 29 80.76 是 4 3 VDLP×3次 未缓解 C3后持续缓解，7.9个月后失访 4 男 27 48.24 是 3 1 VDCLP MRD-CR 持续缓解 5 女 54 89.40 否 8 1 VDCLP MRD-CR 持续缓解 6 男 58 92.00 是 4 3 VDLP、VDCLP、MEA+地塞米松+维奈克拉 未缓解 C3后缓解，19.1个月后复发，20.7个月后死亡 7 男 38 51.30 是 4 1 VDLP MRD-CR 持续缓解 8 男 48 89.58 否 4 1 L-ASP+CVAD+PD-1单抗+托法替布 MRD-CR 持续缓解，6.5个月后失访 9 男 43 91.33 是 4 1 VDCLP+索拉非尼 MRD-CR 持续缓解 10 男 22 77.69 是 4 1 Hyper-CVAD courseA MRD-CR C1后缓解，15.4个月后复发并失访 11 女 56 44.48 是 3 1 mini-HCVD+吉瑞替尼+维奈克拉 MRD-CR 持续缓解 12 女 24 58.66 是 3 1 VDCP MRD-CR 持续缓解 13 男 50 80.00 是 4 1 HAG+地塞米松+阿扎胞苷+维奈克拉 MRD-CR 持续缓解 14 男 61 61.20 是 3 2 Hyper-CVAD courseA、CAM 未缓解 C2后缓解，5.3个月后复发，C3后再次缓解 15 女 69 50.55 是 1 1 MEA+维奈克拉 MRD+CR C1后缓解，7.5个月后复发，9.6个月后死亡 VDLP：长春新碱+柔红霉素+左旋门冬酰胺酶+地塞米松；VDCLP：长春新碱+柔红霉素+环磷酰胺+左旋门冬酰胺酶+地塞米松；MEA：米托蒽醌+依托泊苷+阿糖胞苷；L-ASP：左旋门冬酰胺酶；CVAD：环磷酰胺+长春新碱+多柔比星+地塞米松；Hyper-CVAD courseA：环磷酰胺+长春新碱+多柔比星+地塞米松+甲氨蝶呤(鞘注)+阿糖胞苷(鞘注)；mini-HCVD：环磷酰胺+长春新碱+地塞米松+甲氨蝶呤+阿糖胞苷；VDCP：长春地辛+多柔比星+环磷酰胺+地塞米松；HAG：高三尖杉酯碱+阿糖胞苷+粒细胞集落刺激因子；CAM：环磷酰胺+阿糖胞苷+巯基嘌呤。 
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表 2 患者临床特征与预后的关系
临床特征 第1个疗程后MRD-CR率 P 性别 1.000 男 63.6%(7/11) 女 75.0%(3/4) 年龄 0.416 ≥43岁 62.5%(5/8) < 43岁 71.4%(5/7) 骨髓原始细胞比例 0.573 ≥71% 75.0%(6/8) < 71% 57.1%(4/7) 外周血白细胞 0.504 ≥8×109/L 75.0%(6/8) < 8×109/L 57.1%(4/7) 外周血血红蛋白 0.925 ≥74 g/L 75.0%(6/8) < 74 g/L 57.1%(4/7) 外周血血小板 0.948 ≥102×109/L 75.0%(6/8) < 102×109/L 57.1%(4/7) 是否合并基因异常 0.505 是 58.3%(7/12) 否 100.0%(3/3)
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表 3 患者初治时骨髓血免疫分型
患者编号 流式免疫分型 1 表达CD7 st、CD117 part、CD34、cCD3、CD38、TdT dim、CD99 st、CD13 part、HLA-DR part、CD33 part、CD5 part 2 表达HLA-DR、CD5 dim、CD7、CD34、CD38、cCD3、TdT 3 表达CD7 st、CD34、cCD3 part、CD38 part、CD33、CD56、CD123 part、CD99 st、弱表达cCD79a、CD13 4 表达CD7 st、CD38、CD33 part、CD2、CD99、HLA-DR part，弱表达cCD3、TdT 5 表达CD34、CD117 part、CD7、cCD3、cCD79a part、CD38、CD71 part、CD99 st，弱表达CD123、CD5、CD10 6 表达CD2、CD5、CD7、CD13、CD10、CD34、CD38、CD99、CD117、cCD3 7 表达CD34、CD7、cCD3、CD45 dim、CD99 st、CD117 dim、CD33、CD5 8 表达CD2 dim、CD7、CD3 dim、CD56 part、cCD3、TDT、CD99 st，弱表达CD34 9 表达CD34 part、CD117、CD7 dim、CD2、cCD3part、CD13、CD38、HLA-DR、CD99 st 10 表达CD7、CD2、CD5 part、CD4 part、CD34 part、cCD3、CD38 part、TDT part、CD99 st，弱表达CD3 11 表达CD7、CD2、cCD3、CD34、CD117、CD13、CD38、HLA-DR、CD99 st、CD123 dim 12 表达CD7 st、CD34 part、cCD3、CD38、TDT、CD10、CD99 st、CD3、CD5，弱表达CD2、CD56 13 表达CD34、CD33、CD7，弱表达CD5、CD10、cTdT、cCD3 14 表达CD7、CD34、HLA-DR、CD13、CD33、CD99、cCD3、CD5 15 表达CD33、CD38、CD34、CD7，弱表达CD5 dim、HLA-DR dim、CD117、CD13 dim、cCD3 dim
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表 4 患者初治时异常基因表型
患者编号 异常基因 2 NRAS、JAK1、RUNX1、PHF6、JAK3、NOTCH1 3 NF1、ETV6、KMT2C、FLT3 4 JAK3、PHF6、BRAF、FAT1、NOTCH1、GATA2 6 PHF6、NOTCH1、JAK1、JAK3 7 NOTCH1、GART、IKZF1、ETV6 9 WT1 10 SIL-TAL1 11 WT1、FLT3、SETD2、MEF2D、NUP214、CSMD1、EP300、REV3L、HIST1H1E 12 HOX11L2 13 NOTCH1、NRAS 14 WT1、EVI1、CBL、DNMT3A、ETV6、NOTCH1、PTPN11、IKZF1 15 SET-CAN、BCOR、ETV6、FOXO1、IDH1、JAK1、JAK3、KMT2B、NOTCH1、PHF6、RET、SRP72
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