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. 2025 Feb 20:16:1543099.
doi: 10.3389/fimmu.2025.1543099. eCollection 2025.

Impact of hyperhydration on fluid overload and hematopoietic cell transplant after post-transplant cyclophosphamide-based graft-versus-host-disease prophylaxis

Diana T Samuels #  1 , Janny M Yao #  1 , Yazeed Samara  2 , Dongyun Yang  3 , Sally Mokhtari  4 , Katrin Tiemann  4 , Salman Otoukesh  2 , Shukaib Arslan  2 , Hoda Pourhassan  2 , Stephanie Wu  5 , Amanda Blackmon  2 , Vaibhav Agrawal  2 , Idoroenyi Amanam  2 , Haris Ali  2 , Amandeep Salhotra  2 , Ibrahim Aldoss  2 , Brian Ball  2 , Paul Koller  2 , Ahmed Aribi  2 , Karamjeet Sandhu  2 , Vinod Pullarkat  2 , Andrew Artz  2 , Eileen Smith  2 , Forrest Stewart  2 , Pamela Becker  2 , Anthony Stein  2 , Guido Marcucci  2 , Stephen J Forman  2 , Ryotaro Nakamura  2 , Monzr M Al Malki  2
Affiliations

Impact of hyperhydration on fluid overload and hematopoietic cell transplant after post-transplant cyclophosphamide-based graft-versus-host-disease prophylaxis

Diana T Samuels et al. Front Immunol. .

Abstract

Introduction: Hemorrhagic cystitis (HC) is an early complication after hematopoietic cell transplant (HCT) with post-transplant cyclophosphamide (PTCy). Hyperhydration can reduce HC, but may lead to fluid overload (FO), which has been associated with higher non-relapse mortality (NRM) after HCT.

Methods: The objectives of this study were to grade FO between days 3 and 8 based on weight gain, diuretic therapy, and FO-related organ dysfunction and analyze the impact of FO on non-relapse mortality (NRM) and subsequently on overall survival (OS) of patients undergoing HCT with PTCy-based GvHD prophylaxis.

Results: Two hundred seventy-five patients who received PTCy at City of Hope from 2009 to 2018 were included. A majority, 270 (98%) patients were diagnosed with early FO from day 3-8 post HCT, of whom 248 (92%) experienced mild to moderate (grade 1-2) FO, and 22 (8%) experienced severe (grade 3-4) FO. Day 100 NRM was significantly higher in patients with grade 3-4 FO compared to patients with grade 0-1 (59.1 vs 1.7%, CI: 0.006-0.053p<0.001) and grade 2 (59.1 vs 8.8%, CI: 0.043-0.178, p<0.001) FO. At 2 years, OS and DFS were significantly lower in patients who experienced grade 3-4 FO compared to patients who had grade 0-1 FO (31.8% vs 68.2%, CI: 0.616-0.755, p<0.001) and grade 2 FO (31.8% vs 62.5%; CI: 0.527-0.741, p<0.001). Additionally, each 5% weight gain from baseline was associated with higher NRM (HR=1.91, 95%CI: 1.64-2.23, p<0.001).

Conclusion: Almost all patients undergoing hyperhydration for PTCy-induced HC will present with FO. Grade 3-4 FO is uncommon and associated with poor clinical outcomes. Weight gain could be used as an early and possibly modifiable indicator of FO.

Keywords: allogeneic hematopoietic cell transplantation; fluid overload; fluid retention; fluid toxicity; hemorrhagic cystitis; hyperhydration; post-transplant cyclophosphamide; weight gain.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.

Figures

Figure 1
Figure 1
Patient identification.
Figure 2
Figure 2
Outcomes comparing Grade 0-1, 2, and 3-4 FO patients. Cumulative incidence of (A) Non-relapse mortality. (B) Relapse. Kaplan Meier curves of (C) Disease-free survival, (D) Overall survival.
Figure 3
Figure 3
Linear association between weight gain and overall survival.
See this image and copyright information in PMC

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