Table 1_Impact of hyperhydration on fluid overload and hematopoietic cell transplant after post-transplant cyclophosphamide-based graft-versus-host-disease prophylaxis.docx

IntroductionHemorrhagic 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.
MethodsThe 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.
ResultsTwo 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).
ConclusionAlmost 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.

引言：出血性膀胱炎（Hemorrhagic Cystitis, HC）是采用移植后环磷酰胺（Post-transplant Cyclophosphamide, PTCy）方案行造血细胞移植（Hematopoietic Cell Transplant, HCT）后的早期并发症。水化治疗可降低HC发生率，但可能引发液体超负荷（Fluid Overload, FO），而后者与HCT后更高的非复发死亡率（Non-relapse Mortality, NRM）相关。
方法：本研究旨在基于体重增幅、利尿治疗及FO相关器官功能障碍，对移植后第3至8天的液体超负荷进行分级，并分析液体超负荷对采用PTCy方案预防移植物抗宿主病（Graft-versus-host Disease, GvHD）的HCT患者的非复发死亡率（NRM）及总生存期（Overall Survival, OS）的影响。
结果：本研究纳入2009年至2018年间于希望之城接受PTCy治疗的275例患者。其中270例（98%）患者在HCT后第3至8天被诊断为早期FO，包括248例（92%）轻中度（1-2级）FO患者，以及22例（8%）重度（3-4级）FO患者。与0-1级FO患者相比，3-4级FO患者的移植后第100天非复发死亡率显著更高（59.1% vs 1.7%，置信区间[CI]: 0.006-0.053，p<0.001）；与2级FO患者相比，3-4级FO患者的移植后第100天非复发死亡率同样显著更高（59.1% vs 8.8%，CI: 0.043-0.178，p<0.001）。随访2年时，与0-1级FO患者相比，3-4级FO患者的总生存期（OS）及无病生存期（Disease-Free Survival, DFS）均显著更低（OS: 31.8% vs 68.2%，CI: 0.616-0.755，p<0.001；DFS: 31.8% vs 62.5%，CI: 0.527-0.741，p<0.001）。此外，每较基线体重增加5%，均与更高的非复发死亡率相关（风险比[Hazard Ratio, HR]=1.91，95%CI: 1.64-2.23，p<0.001）。
结论：几乎所有因PTCy诱导HC而接受水化治疗的HCT患者都会出现FO。3-4级FO较为少见，但与不良临床结局相关。体重增幅可作为FO的早期且可能可干预的评估指标。