Continuous Infusion Vs Intermittent Bolus Mesna with Post-Transplant Cyclophosphamide Following Hematopoietic Stem Cell Transplantation

Post-transplant cyclophosphamide (PTCy) is an effective strategy used in the prevention of graft-vs-host-disease (GVHD) during hematopoietic stem cell transplantation (HCT). Hemorrhagic cystitis (HC) is a major complication associated with high-dose cyclophosphamide in 10-40% of patients [Urology; 100:16-19]. Sodium 2-mercaptoethanesulfonate (MESNA) binds and inactivates acrolein in the urinary tract, preventing tissue injury. While international guidelines endorse MESNA, there is no consensus regarding the optimal method of administration with high-dose cyclophosphamide (J Clin Oncol.2002;20:2895–2903). Historically, our institution administered MESNA as 3 intermittent boluses (IB) at hours 0, 3, and 6 of the cyclophosphamide administration. From September 2022 onwards, we investigated the use of MESNA as a 24-hour continuous infusion (CI) starting with cyclophosphamide to reduce the incidence of HC after PTCy.The primary endpoint of this study was the incidence of all-grade HC based on the common terminology criteria for adverse events (CTCAE) after PTCY-based HCT. Key secondary outcomes included grade 2-4 HC incidence, non-viral and viral-associated (BK virus and adenovirus) HC incidence, median time to HC, and 100-day mortality.From September 2022 to May 2023, 15 patients received PTCy with CI MESNA. This cohort was matched in a 1:2 ratio to the 30 previous patients who received IB MESNA with PTCy prior to the protocol change (February 2021- September 2022). Baseline characteristics were similar between both arms (Table 1). The majority received reduced-intensity conditioning and a haploidentical HCT. The most common diagnoses were acute leukemia, myelodysplastic syndrome, and sickle cell disease.There was no statistically significant difference in the incidence of all grade HC (CI 93% vs IB 80%, p=0.245) or grade 2-3 HC (40% vs 33%, p=0.66). Two patients in the IB group required bladder irrigation or cystoscopy, and there were no instances of grade 4 HC in either group. Rates of non-viral associated HC were similar (60% vs 63%, p=0.828). The CI MESNA arm had a non-statistically significant higher incidence of viral-associated HC (33% vs 17%, p=0.205). Median time to HC development was similar between both groups (7.5 days vs 7 days, p=0.905). After adjusting for conditioning intensity in the regression analyses, a nonsignificant difference between CI and IB MESNA remained for all outcomes. All patients in both arms were alive at Day +100.In this single-center, retrospective analysis, dosing MESNA either CI or IB with PTCy did not significantly affect the incidence or timing of HC, which was mainly limited to grade 1 in both groups. A larger prospective trial evaluating different dosing strategies may help decide the optimal strategy for administering MESNA to minimize morbidity, hospitalization, blood transfusions, and financial burden associated with HC.