Circadian rhythm-guided cellular therapy in hematologic malignancies: mechanisms, clinical evidence, and optimization strategies

Circadian rhythms are endogenous 24-hour timing systems that coordinate hematopoiesis and immune function through central and peripheral clocks. Increasing evidence indicates that the initiation and progression of hematologic malignancies are frequently accompanied by circadian disruption, which not only contributes to malignant transformation and disease progression but also anti-tumor immunity and variable treatment responses. Cellular therapies, particularly hematopoietic stem cell transplantation (HSCT) and chimeric antigen receptor T-cell therapy (CAR-T), have emerged as transformative modalities for hematologic malignancies, demonstrating remarkable clinical efficacy. However, their outcomes and toxicities are significantly influenced by circadian regulation. This review summarizes circadian mechanisms in hematologic malignancies and chronotherapy evidence for HSCT and CAR-T. And we discuss chronotherapeutic opportunities, including timed cell collection, manufacturing, infusion, and post-treatment care. We further highlight the clinical relevance of individualized circadian phase assessment as a foundation for personalized treatment scheduling. Collectively, integrating circadian principles into hematologic cellular therapy may improve engraftment, enhance antitumor efficacy, reduce toxicity, and provide a practical framework for more precise and personalized treatment.