Severity of Acute Graft-versus-Host Disease and Associated Healthcare Resource Utilization, Cost, and Outcomes

Acute graft-versus-host disease (aGVHD) contributes to poor outcomes and increased healthcare resource utilization (HRU) after allogeneic hematopoietic stem cell transplantation (HCT). However, HRU and the economic burden of aGVHD based on severity of the disease is not well characterized. Our study cohort comprised 290 adults who underwent allogeneic HCT between 2010 and 2018. Costs, HRU, and all-cause mortality in the 100-day and 365-day periods after HCT were compared between patients with aGVHD and those without aGVHD. The impact of aGVHD severity and gastrointestinal (GI) involvement on mortality, HRU, and economic burden was also evaluated. Medical costs and total hospital length of stay (LOS) were retrieved from administrative data that allocate costs to services based on departmental input for resource use and were adjusted to 2018 dollars. The Wilcoxon rank-sum test was used to compare the number of inpatient days and total costs. Multivariable linear regression was fitted on log-transformed costs. Compared with patients without aGVHD, those with aGVHD had a significantly greater median hospital LOS (28 days versus 22 days) and higher rates of intensive care unit (ICU) admission (13% versus 6%) and rehospitalization (59% versus 38%) during the first 100 days post-HCT. The presence of grade I-II aGVHD significantly prolonged the hospital LOS by a median of 3 days and increased the readmission rate by 18%, whereas grade III-IV aGVHD was associated with a nearly 30% increase in the readmission rate and a doubling of inpatient LOS, ICU admission rate, and mortality in the first 100 days post-HCT. Compared with the absence of aGVHD, lower GI involvement in aGVHD was also associated with increased risk of readmission (30%) and twice as many inpatient days, doubling the likelihood of ICU admission and mortality over the first 100 days. Similar findings were observed over days 101 to 365 post-HCT. The mean cost attributable to aGVHD regardless of grade was $60,923 in the first 100 days post-HCT. This cost varied by grade. The mean aGVHD- attributable costs were $18,071 for grade I, $36,115 for grade II and $120,929 for grade III/IV aGVHD and $114,668 for aGVHD involving the lower GI tract. In the 101- to 365-day period, the mean attributable aGVHD cost regardless of grade was $17,527. This cost also varied by grade. There were no additional aGVHD-attributable costs for grade I, but the mean aGVHD-attributable costs were $9743 for grade II, $62,220 for grade III/IV, and $55,724 for aGVHD with lower GI involvement compared with the controls without aGVHD. High-grade aGVHD and GI involvement in aGVHD, especially lower GI aGVHD, is associated with a considerably increased mortality and healthcare economic burden. Therefore, it is imperative that new therapeutic strategies be developed for this patient population.