研究目的：

   分析WT1基因（+）成人急性淋巴细胞白血病的临床特征、疗效及预后影响因素。

研究方法：

   选取白血病诊疗中心自2015.6.1-2018.12.31期间收治的共109例WT1基因(+)的初诊急性淋巴细胞白血病患者，回顾性分析其临床特征、疗效及预后相关因素。

结果：

WT1基因(+)患者占同时期我中心收治初诊急性淋巴细胞白血病患者的64.1%（109/170）。男女比例1.66:1（68/41），年龄范围14-64岁，中位年龄30岁。初诊白细胞数、血红蛋白、血小板的中位值分别为22.1（0.59-437.2）×10⁹/L、97（39-161）g/L、52（5-478）×10⁹/L。免疫表型中B-ALL占80.73%（88/109），以Common B-ALL为主，T-ALL占19.27%（21/109）。初诊时骨髓WT1基因相对表达定量中位值为17.86%（2.06%-973.21%），与患者年龄、性别、流式免疫分型、初诊血小板数无显著相关，而初诊白细胞数高于50×10⁹/L（P=0.002）、伴有MLL基因重排者（P=0.000）WT1基因相对表达定量显著增高，伴有BCR/ABL融合基因者（P=0.000）则WT1基因相对表达定量显著减低。随诊至2020年6月30日，中位随访时间23（1-60）个月，预期4年总生存率、无病生存率分别为59.8%±5.3%、52.0%±8.4%，与WT1基因阴性组无明显统计学差异。Cox模型多因素分析显示诱导化疗后未缓解（P=0.03）是影响总生存的危险因素，伴有MLL基因重排（P=0.014）是影响无病生存的独立危险因素，而性别、年龄、初诊白细胞数、免疫表型、初诊WT1基因定量、伴有BCR/ABL融合基因、诱导化疗后WT1基因是否转阴等均对生存影响无明显统计学差异。

结论：

  WT1基因在成人急性淋巴细胞白血病中较为常见，初诊高白细胞、伴有MLL基因重排者WT1基因定量显著增高，伴有BCR/ABL融合基因者则WT1基因定量显著减低。诱导化疗后骨髓未缓解、伴有MLL基因重排是影响此类患者生存的独立危险因素。

Objective:

   To analyze clinical features, efficacy and prognostic factors of adult acute lymphoblastic leukemia with the Wilms tumor 1 (WT1) gene.

Methods:

   109 newly diagnosed adult acute lymphoblastic leukemia patients with the Wilms tumor 1 (WT1) gene from June, 2015 to December, 2018 were enrolled. Retrospectively analyzed their clinical features, efficacy and prognostic factors.

Results:

   The incidence frequency of WT1 gene in adult acute lymphoblastic leukemia was 64.1%（109/170）, including 68 males and 41 females. The median age was 30 years old ranged from 14 to 64 years. The median value of leucocyte, hemoglobin and platelet at diagnosis was 22.1（range, 0.59-437.2）×10⁹/L、97（range, 39-161）g/L and 52（range, 5-478）×10⁹/L, respectively. B-cell phenotype accounts for 80.73%（88/109）of all the cases, most of which being present in common-B-ALL, while T-ALL accounts for the rest 19.27%. The median relative expression value of WT1 gene at diagnosis was 17.86%(range, 2.06%-973.21%), which was no  significantly related to age, gender, immune phenotype or platelet value at diagnosis . Patients with MLL rearrangement and higher leucocyte (≥50×10⁹/L) at diagnosis had significantly higher WT1 gene expression, while patients with BCR-ABL fusion expressed significantly lower WT1 gene value. The follow up period ended in June 2020 with a median follow up time of 23(range, 1-60) months. The estimated 4-year-OS and 4-year-DFS was 59.8%±5.3%, 52.0%±8.4%, respectively, which showed no obvious differences with WT1 gene negative group. Cox regression multivariate analysis revealed that poor prognostic factors influencing survival included MRD positivity after induction chemotherapy (P=0.03) and MLL rearrangement (P=0.014) only.

Conclusion:

   WT1 gene was relative common at diagnosis in adult acute lymphoblastic leukemia. Patients with MLL rearrangement and higher leucocyte (≥50×10⁹/L) at diagnosis had significantly higher WT1 gene expression, while patients with BCR-ABL fusion expressed significantly lower WT1 gene value. Positive MRD after induction chemotherapy and accompanying with MLL rearrangement were unfavourable prognostic factors for survival.