Serviço de Hematologia e Transplantação de Medula, Centro Hospitalar Universitário Lisboa Norte, Lisbon, Portugal; Laboratório de Genética, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.
Serviço de Hematologia e Transplantação de Medula, Centro Hospitalar Universitário Lisboa Norte, Lisbon, Portugal.
Clin Lymphoma Myeloma Leuk. 2024 Feb;24(2):e13-e20. doi: 10.1016/j.clml.2023.09.010. Epub 2023 Sep 29.
Apart from transplantation, only azacitidine demonstrated a survival benefit in a phase III study in higher-risk myelodysplastic syndromes (MDS). The approved regimen is 75 mg/m/day for 7 consecutive days, imposing a logistic challenge for outpatient weekend administration. Schedules with 5 days and 7 days with a weekend break (5 + 2) have been used for convenience despite the lack of strong scientific support. Most studies of alternative schedules were performed in lower-risk MDS and with dose reduction in the 5-day schedules.
We performed a single-center, retrospective cohort study to compare full-dose azacitidine (7 × 75 mg/m) administration in 5-day and 5 + 2-day schedules in a higher-risk MDS cohort. We evaluated 100 patients for overall survival and a subsample (49 patients) for acute myeloid leukemia-free survival (AMLFS), probability of infections and transfusion burden. Kaplan-Meier analysis and Cox models were used for survival analyses. Linear and logistic regressions were applied for univariate and multivariate assessment.
After a median follow-up of 10.8 months, patients treated with a 5-day schedule had a median overall survival of 12.5 months versus 15.0 months in the 5+2 group: HR 0.95 (95% CI, 0.57-1.56); P= .83. AMLFS was also similar between groups: HR 1.70 (95% CI, 0.70-4.14); P = .24. Azacitidine schedules were not predictive of infections nor number of red blood cell or platelet transfusions in multivariate analyses.
In higher-risk MDS, full-dose azacitidine (7 × 75 mg/m) can be administered both in 5 days and in 7 days with a weekend break with no significant difference in survival, infection or transfusional outcomes.
除了移植，在一项高危骨髓增生异常综合征（MDS）的 III 期研究中，阿扎胞苷显示出生存获益。批准的方案为 75mg/m/天，连用 7 天，这对门诊周末给药提出了逻辑挑战。尽管缺乏强有力的科学依据，但为了方便起见，已经使用了连续 5 天和 7 天并在周末休息（5+2）的方案。大多数替代方案的研究都是在低危 MDS 中进行的，并且在 5 天方案中进行了剂量减少。
我们进行了一项单中心、回顾性队列研究，比较了高危 MDS 队列中 5 天和 5+2 天方案中全剂量阿扎胞苷（7×75mg/m）的给药。我们评估了 100 例患者的总生存情况和亚组（49 例）的急性髓性白血病无复发生存（AMLFS）、感染概率和输血负担。采用 Kaplan-Meier 分析和 Cox 模型进行生存分析。线性和逻辑回归用于单变量和多变量评估。
中位随访 10.8 个月后，5 天方案组患者的中位总生存时间为 12.5 个月，5+2 组为 15.0 个月：HR 0.95（95%CI，0.57-1.56）；P=.83。两组间 AMLFS 也相似：HR 1.70（95%CI，0.70-4.14）；P=.24。多变量分析中，阿扎胞苷方案与感染或红细胞或血小板输注次数均无相关性。
在高危 MDS 中，75mg/m/天的全剂量阿扎胞苷可连续 5 天或 7 天给药，周末休息，在生存、感染或输血结局方面无显著差异。
