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探讨维奈克拉（Venetoclax，Ven）联合多药化疗治疗复发难治早期前体T淋巴细胞白血病（R/R ETP-ALL）患者的疗效及安全性。

回顾性分析2018年12月至2022年2月在苏州大学附属第一医院住院治疗的15例R/R ETP-ALL患者的临床资料。再诱导治疗以Ven为基础联合多药化疗，其中8例联合去甲基化药物，4例同时联合去甲基化药物和HAAG方案，2例同时联合去甲基化药物和CAG预激方案，1例联合克拉屈滨。Ven用法为100 mg第1天，200 mg第2天，400 mg第3～28天，口服；联合唑类抗真菌药物时减量至100 mg/d。

15例R/R ETP-ALL患者中，男10例，女5例，中位年龄35（12～42）岁。难治4例，复发11例。用药第21天疗效：完全缓解（CR）率为60.0％（9/15），CR伴血液学不完全恢复（CRi）率为6.7％（1/15），总有效率（ORR）为66.7％。所有患者12个月总生存（OS）率为60.0％，中位OS时间为17.7个月；全部CR患者12个月无病生存（DFS）率为60.0％，中位DFS时间未达到。14例（93.3％）患者发生了3级及以上血液学不良反应，所有患者经治疗后造血功能恢复且无致死性大出血发生；无患者出现神经系统不良反应及肿瘤溶解综合征，同时无3级及以上脏器不良反应发生。

Ven联合多药化疗治疗R/R ETP-ALL疗效值得肯定，治疗相关不良反应可耐受。

To explore the efficacy and safety of Venetoclax combined with multidrug chemotherapy in patients with relapsed or refractory early T-cell precursor acute lymphoblastic leukemia（R/R ETP-ALL）.

This study retrospectively analyzed 15 patients with R/R ETP-ALL who received Venetoclax combined with multidrug chemotherapy from December 2018 to February 2022. Among them, eight cases were combined with demethylated drugs, four cases were combined with demethylated drugs and HAAG chemotherapy regimen, two cases were combined with demethylated drugs and CAG regimen, and one case was combined with Cladribine. Specific usage and dosage of Venetoclax: 100 mg on day 1, 200 mg on day 2, 400 mg on day 3–28, orally; when combined with azole antifungal drugs, dosage was reduced to 100 mg/d.

Fifteen patients（10 males and 5 females）with R/R ETP-ALL were treated with Venetoclax and multidrug chemotherapy with a median age of 35（12–42）years old. Of 4 refractory and 11 relapsed patients, the efficacy was evaluated on the 21th day following combined chemotherapy: the overall response rate, the complete response（CR）rate, and the CR with incomplete hematological recovery（CRi）rate were 67.7％（10/15）, 60.0％（9/15）, and 6.7％（1/15）, respectively. For the overall study population, the 12-month overall survival（OS）rate was 60.0％, and the median OS was 17.7 months. The disease-free survival（DFS）rate of all CR patients at 12 months was 60.0％, and the median DFS did not reach. About 14 patients had Ⅲ–Ⅳ hematological toxicity, but these adverse reactions were all controllable. No adverse reaction in the nervous system and tumor lysis syndrome occurred in this study, and no adverse reaction of organs above grade Ⅲ occurred.

Venetoclax combined with multidrug chemotherapy may be a safe and promising treatment option for patients with R/R ETP-ALL.

早期前体T淋巴细胞白血病（ETP-ALL）是急性T淋巴细胞白血病（T-ALL）的一种特殊类型，发病率低，约占T-ALL的17％[1]，在分子免疫表型、细胞遗传学及预后等方面具有高度的异质性，具有对常规化疗耐药、复发风险高及预后差的特点[2]–[3]。异基因造血干细胞移植（allo-HSCT）已被证实可提高ETP-ALL患者的生存率[4]–[5]，对于复发难治（R/R）ETP-ALL患者，行allo-HSCT前再次实现完全缓解（CR）至关重要。然而，复发及耐药后的最佳再诱导治疗方案尚无定论。BCL-2抑制剂维奈克拉（Ven）是一种小分子抑制剂，直接与BCL-2蛋白结合，置换促凋亡蛋白并恢复凋亡过程，ETP-ALL高度依赖BCL-2，在体外实验和体内治疗中对Ven均敏感。现将本中心应用Ven联合去甲基化药物及预激方案治疗的15例R/R ETP-ALL患者的疗效及安全性报道如下。

1. 病例：以2018年12月至2022年2月在苏州大学附属第一医院住院治疗的15例R/R ETP-ALL患者为研究对象，回顾性分析患者的临床资料，诊断符合《中国成人急性淋巴细胞白血病诊断与治疗指南（2021年版）》[6]，所有患者根据骨髓细胞形态学、免疫表型分析、细胞遗传学、分子生物学（MICM）进行诊断分型并确诊。

2. 治疗方法：再诱导治疗以Ven为基础联合多药化疗。Ven标准方案：Ven 100 mg第1天，200 mg第2天，400 mg第3～28天，口服。药物用量及疗程根据不良反应及一般状况调整，1例患者因中性粒细胞减少28 d内均采用100 mg/d，因出现粒细胞缺乏（粒缺）需要伏立康唑预防真菌感染的患者，Ven减至100 mg/d，重度粒缺（