Restrictive versus standard hyperhydration during high-dose cyclophosphamide for hematopoietic stem cell transplantation: a retrospective cohort study

Purpose: Cyclophosphamide is a commonly used chemotherapeutic agent in hematopoietic stem cell transplantation (HSCT), but its use can lead to adverse effects such as hemorrhagic cystitis (HC) and electrolyte disturbances, including hyponatremia. While standard hydration protocols are used to mitigate these risks, the optimal regimen remains unclear. This study explores the impact of a restrictive hydration regimen on HC incidence and electrolyte imbalances in patients undergoing high-dose cyclophosphamide treatment as part of HSCT conditioning. Methods: A retrospective cohort study was conducted at Amsterdam UMC, including patients who received high-dose cyclophosphamide as part of HSCT between 2016 and 2024. Patients were grouped based on hydration protocols: an original regimen (5 L of NaCl 0.45%/dextrose 2.5% per day) and a new restrictive regimen (1.5 L/m²/day of 0.65% NaCl). The primary endpoint was the incidence of HC, while secondary endpoints included sodium and potassium changes, fluid overload (measured by furosemide use), and clinical outcomes. Results: HC occurred in 10/386 (2.6%) patients in the original protocol and 1/69 (1.4%) in the restrictive protocol (odds ratio [95% confidence interval]: 0.55 [0.03–2.96], p = 0.57). Clinically relevant hyponatremia was less common with the restrictive regimen (1.4%) than with the original protocol (4.4%), though the difference was not significant (p = 0.27). On the other hand, patients receiving the restrictive regimen showed more clinically relevant hypokalemia (8.7% vs 5.9%, p = 0.28). Fluid overload, as indicated by furosemide use, was lower in the restrictive group albeit not statistically significant. Conclusion: In this retrospective single-center cohort, we did not observe a higher incidence of HC or electrolyte imbalances with a restrictive hydration regimen compared to the original regimen.