Assessing the Impact of Fluid Overload on Outcomes after Allogeneic Hematopoietic Cell Transplantation

Background Fluid overload (FO) is common after allogeneic HCT and may associate with various other organ and transplant complications. Although largely unexplored as a hazard in HCT, a group has recently reported that FO may be an independent risk factor for patient outcomes in this setting (doi:10.1016/j.bbmt.2017.08.021.). Methods We conducted a retrospective study of consecutive allogeneic HCT recipients from 2009 to 2022 at our institution to determine the prevalence of FO, according to the criteria defined by Rondon et al, and its association with patient outcomes. We documented maximal grade of FO between date of admission and day +30 or patient discharge, whichever occurred first, with particular focus on FO beyond grades 0 and 1 (2: symptomatic fluid retention requiring ongoing diuretic therapy, weight gain ≥10% to <20%; 3: weight gain ≥20% unresponsive to diuretic therapy and possible organ dysfunction; 4: progressive dysfunction of more than one organ system or requiring intensive care). Results A total of 313 allo-HCT patients were included: 181 men (58%); median age 49 years (16-71); 61% acute leukemia, 19% chronic lymphoid and 16% chronic myeloid malignancies, 4% other indications; 39% matched siblings, 38% cord blood, 18% haploidentical and 14% unrelated donors; 51% myeloablative conditioning). One hundred and twenty-five patients (40%) had FO as defined above: 74 grade 1 (24%) and 51 grade = or > 2 (16%). In keeping with weight increase, grade = or > 2 FO cases had a median +1512 mL (236-3800 mL) positive fluid balance. Grade = or > 2 FO was more common in HCT from alternative donors (p<0.001), in patients who develop acute kidney injury (29% grade = or > 2; p<0.001), SOS/VOD (13%; p<0.001) or TA-TMA (11%; p=0.001), and those requiring total parenteral nutrition (29%; p=0.007) or admission to ICU (12%; p<0.001), but did not associate with other patient and HCT factors such as sex, diagnosis, comorbidity score, conditioning intensity, baseline pre-HCT creatinine, or acute GVHD (data not shown). Patients with grade = or > 2 FO had significantly lower overall survival (OS) than those with no FO or grade 1, both early at day +100 (61% vs 93%; p<0.001) and later at one year after HCT (43% vs 69%; p<0.001), respectively (Figure 1). Multivariate analysis showed that the impact of FO on OS was independent from other complications and factors associated with FO and with transplant outcome (Table 1). Conclusions FO = or > grade 2 is relatively frequent in the first 30 days during the initial admission for allogeneic HCT, and associates with lower OS early at day +100 and at one year. Although FO associates with other patient and transplant characteristics and complications, the impact on FO on OS is independent from these other concomitant factors. These findings warrant further investigation, including potential early intervention, on FO as a risk factor in allogeneic HCT.