(086) Evaluation of an Institutional Hydration Protocol for Post-Transplant Cyclophosphamide in Allogeneic Hematopoietic Stem Cell Transplant Recipients

Poster Abstract: A major complication after allogeneic hematopoietic stem cell transplant (allo-HSCT) in patients who receive post-transplant cyclophosphamide (PTCy) is hemorrhagic cystitis (HC). Cyclophosphamide is an alkylating agent that prevents graft-versus-host-disease (GVHD) through depletion of alloreactive T cells while sparing regulatory T cells. A toxic metabolite of cyclophosphamide, acrolein, can cause HC through urothelial damage which presents as pain and/or hematuria and can progress to renal dysfunction. Hydration with PTCy is recommended to dilute the urine and maintain adequate urine output. However, there is no consensus regarding the optimal amount or duration of hydration. Aggressive hydration is preferred but can lead to post-transplant fluid overload. At the Cellular Immunotherapies and Transplant Program at VCU Health’s Massey Cancer Center, the previous PTCy hydration protocol was normal saline (NS) 3000 mL/m2/day (maximum 250 mL/hr) starting 4 hours before PTCy until 24 hours after PTCy completion. Recently, an empirical reduction in this protocol was implemented due to anecdotal evidence of increased fluid overload complications in patients receiving PTCy at our institution. The new PTCy hydration protocol is 2 mL/kg/hr (maximum 150 mL/hr) NS starting 2 hours before PTCy until 12 hours after PTCy completion.

The aim of this project is to compare the rates of fluid overload complications and HC between these two hydration protocols.

This is a retrospective, quality improvement project evaluating allo-HSCT recipients between December 2021 to December 2023. Patients will be included if they were at least 18 years old at the time of allo-HSCT and received PTCy for GVHD prophylaxis. Patients that were pregnant and incarcerated were excluded. The primary outcome is occurrence of clinically significant fluid overload, defined as one of the following criteria within 14 days of PTCy: 1) fluid overload sequelae (pulmonary edema or pleural effusions on pulmonary imaging) or 2) requirement of fluid removal intervention (diuretics or ultrafiltration). Secondary endpoints include occurrence of HC, significant weight gain, and transfer to intensive care unit among others. Data will be collected from electronic patient health records in Epic. Data will be analyzed via independent t-tests and Chi squared tests.

Results and conclusions are pending. The reduced hydration protocol for PTCy recipients is hypothesized to reduce fluid overload complications while providing adequate prophylaxis against HC. This quality improvement project will characterize the impact of these protocol amendments on early-post transplant outcomes at our institution.

References (must also be included in final poster): Arango M, Cardona D. Hemorrhagic Cystitis after Haploidentical Transplantation with Post-Transplantation Cyclophosphamide: Protective Effect of MESNA Continuous Infusion. Biol Blood Marrow Transplant. 2020 Aug;26(8):1492-1496. doi: 10.1016/j.bbmt.2020.04.028. Epub 2020 May 15. PMID: 32417488.
Mac S, Ngo D, Yang D, Chen J, et al. Use of high-dose mesna and hyperhydration leads to lower incidence of hemorrhagic cystitis after posttransplant cyclophosphamide-based allogeneic transplantation. Bone Marrow Transplant. 2021 Oct;56(10):2464-2470.
Nunes NS, Kanakry CG. Mechanisms of Graft-versus-Host Disease Prevention by Post-transplantation Cyclophosphamide: An Evolving Understanding. Front Immunol. 2019 Nov 29;10:2668.