Liu Yu, Wang Zhihui, Chen Tairan, Zhou Lixin, He Qiulian, Deng Xiangping, Long Kejie, Zou Xingli
Department of Hematology, Affiliated Hospital of North Sichuan Medical College, Nanchong, China.
Department of Hematology, Beijing Anzhen Nanchong Hospital of Capital Medical University & Nanchong Central Hospital, Nanchong, China.
Ann Med. 2025 Dec;57(1):2512115. doi: 10.1080/07853890.2025.2512115. Epub 2025 Jun 9.
Cytarabine (Ara-C) is a cornerstone of acute myeloid leukaemia (AML) treatment, particularly in consolidation therapy. Although high-dose cytarabine (HDAC) has been widely adopted for consolidation in AML, intermediate-dose cytarabine (IDAC) is increasingly favoured due to its comparable efficacy and improved tolerability. However, the potential benefit of combining another agent with IDAC during consolidation therapy has yet to be adequately validated.
This retrospective study analyzed 204 newly diagnosed adult AML patients who underwent at least two cycles of consolidation therapy with either IDAC monotherapy ( = 84) or IDAC combined with anthracyclines/homoharringtonine (IDAC-plus, = 120) after complete remission (CR) or complete remission with incomplete count recovery (CRi).
At a median follow-up of 26.5 months, IDAC-plus significantly improved relapse-free survival (RFS) compared to IDAC monotherapy (HR 0.62, = 0.019). Although overall survival (OS) was not significantly different, the IDAC-plus group showed a survival advantage (HR, 0.68; = 0.11). Subgroup analysis identified younger patients (HR = 0.43, = 0.01), male patients (HR = 0.51, = 0.03), patients with better performance status (HR = 0.52, = 0.01), lactate dehydrogenase (LDH) >2 × upper limit of normal (ULN) (HR 0.51, = 0.01), intermediate-risk disease (HR= 0.51 = 0.01), measurable residual disease (MRD) positivity at CR/CRi (HR = 0.48, = 0.03) and patients without hyperleukocytosis (HR = 0.64, = 0.04), can have a more pronounced benefit from IDAC-plus consolidation chemotherapy. IDAC-plus group had more neutropenia (grade ≥3) ( = 0.032), febrile neutropenia ( = 0.039) and documented infection ( = 0.028), but non-relapse mortality (NRM) was similar between the two groups ( = 0.985).
The findings suggest that IDAC-based combination consolidation chemotherapy reduces the risk of relapse in non-transplant AML compared to IDAC alone, particularly in patients with intermediate-risk disease or MRD positivity at the time of achieving CR/CRi, underscoring the need for intensified regimens in these populations.
阿糖胞苷（Ara-C）是急性髓系白血病（AML）治疗的基石，尤其是在巩固治疗中。尽管大剂量阿糖胞苷（HDAC）已被广泛用于AML的巩固治疗，但中剂量阿糖胞苷（IDAC）因其疗效相当且耐受性更好而越来越受到青睐。然而，在巩固治疗期间将另一种药物与IDAC联合使用的潜在益处尚未得到充分验证。
这项回顾性研究分析了204例新诊断的成年AML患者，这些患者在完全缓解（CR）或血细胞计数未完全恢复的完全缓解（CRi）后接受了至少两个周期的巩固治疗，其中单药使用IDAC治疗（n = 84）或IDAC联合蒽环类药物/高三尖杉酯碱（IDAC加，n = 120）。
在中位随访26.5个月时，与IDAC单药治疗相比，IDAC加显著改善了无复发生存期（RFS）（HR 0.62，P = 0.019）。尽管总生存期（OS）没有显著差异，但IDAC加组显示出生存优势（HR，0.68；P = 0.11）。亚组分析确定，年轻患者（HR = 0.43，P = 0.01）、男性患者（HR = 0.51，P = 0.03）、体能状态较好的患者（HR = 0.52，P = 0.01）、乳酸脱氢酶（LDH）>正常上限（ULN）的2倍（HR 0.51，P = 0.01）、中危疾病（HR = 0.51，P = 0.01）、CR/CRi时可测量残留病（MRD）阳性（HR = 0.48，P = 0.03）以及无白细胞增多症的患者（HR = 0.64，P = 0.04），从IDAC加巩固化疗中获益可能更显著。IDAC加组有更多的中性粒细胞减少（≥3级）（P = 0.032）、发热性中性粒细胞减少（P = 0.039）和有记录的感染（P = 0.028），但两组间的非复发死亡率（NRM）相似（P = 0.985）。
研究结果表明，与单独使用IDAC相比，基于IDAC的联合巩固化疗可降低非移植AML的复发风险，尤其是在达到CR/CRi时患有中危疾病或MRD阳性的患者中，强调了在这些人群中强化治疗方案的必要性。
