Association Between the Time of Day of Post‐Transplant Cyclophosphamide Administration and Haemorrhagic Cystitis After Allogeneic Haematopoietic Stem Cell Transplantation

OBJECTIVE: To evaluate the impact of the time-of-day (daytime vs. nighttime) of the infusion of post-transplantation cyclophosphamide (PTCy) on the occurrence of haemorrhagic cystitis (HC) in adult patients undergoing allogeneic haematopoietic stem cell transplantation (allo-HSCT). METHODS: We conducted a retrospective, single-centre cohort study including adult allo-HSCT between January 2014 and December 2022. All patients received PTCy at a dose of 50 mg/kg/day for two consecutive days. Patients were classified according to the timing of the first PTCy dose: daytime (06:00-17:59) or nighttime (18:00-05:59). The primary endpoint was the incidence of Grade II-IV HC. RESULTS: A total of 178 patients were included. Grade II-IV HC occurred in 16.4% and 31.2% of patients following daytime and nighttime administration, respectively (OR 2.31, 95% CI 0.97-5.49; p = 0.079). After adjustment for potential confounders, nighttime administration was associated with higher odds of Grade II-IV HC (adjusted OR 2.82, 95% CI 1.12-7.10; p = 0.028). Grade III-IV HC was more frequent following nighttime administration (4.8% vs. 15.6%; OR 3.68, 95% CI 1.09-12.45; p = 0.043). No significant differences were observed in transplant outcomes. CONCLUSIONS: Nighttime administration of PTCy was associated with a numerically higher incidence of Grade II-IV HC, although the unadjusted primary analysis did not reach conventional statistical significance. This association was statistically significant after adjustment for potential confounders. No detectable differences in transplant outcomes were observed. These findings support prospective evaluation of chronomodulated PTCy administration as a simple, potentially modifiable strategy for reducing treatment-related toxicity after allo-HSCT.