Abstract
Introduction
Hepatic Veno-occlusive disease (VOD) is a potential life threatening complication of hematopoietic cell transplantation (HSCT) and may also occur after chemotherapy (Negrin et al. 2017). Severe VOD characterized by multi-organ failure (MOF) is fatal and associated with high mortality (Coppell et al. 2010). The economic burden of VOD in ALL patients has not been reported in the published literature.
Objective
To investigate the incidence, inpatient mortality and economic burden of VOD among adult B-cell ALL patients in the US.
Methods
This was a retrospective cohort study using Truven Health MarketScan® Commercial and Medicare Supplemental Databases. We first identified the adult B-cell ALL patients. Patients with ≥1 inpatient claims or ≥2 non-diagnostic outpatient claims at least 30 days apart for any ALL diagnosis (ICD-9-CM 204.00-204.02, ICD-10-CM C91.00-C91.02) during 4/1/2009 - 10/31/2016 were extracted. All patients were required to have ≥1 hospitalization with diagnosis-related group in 834-839 on or after the first ALL diagnosis, be ≥18 years old, and have ≥6 months of continuous enrollment prior to the first ALL diagnosis date. Patients with medications for T-Cell ALL during the study period were excluded. VOD patients were then identified based on clinical criteria (Coppell et al. 2010) and expert opinions. VOD patients must have one of the following: 1) a ICD-10-CM code specifically for VOD diagnosis (K76.5), 2) prescription for defibrotide sodium that is indicated for treatment of VOD in the US, 3) at least two VOD symptoms from either Baltimore or Seattle criteria for VOD (ascites, abnormal weight gain, hyperbilirubinemia, or hepatomegaly) within 60 days post HSCT admission, or 4) multi-organ failure (MOF) with liver failure within 60 days post HSCT admission. The VOD index date was the first observed VOD diagnosis date, defibrotide sodium prescription date, or HSCT admission date. HSCT patients were excluded if they had evidence of chronic graft-versus-host disease (GVHD) any time before or 100 days after the VOD index date or if they had acute GVHD or total parenteral nutrition cholestasis during 60 days before or 100 days after the VOD index date. Severe VOD patients were defined as VOD patients with MOF. Patients were followed until the earliest of inpatient death, end of continuous enrollment, end of the study period (10/31/2016), and capped at 100 days. Outcomes included incidence rates of VOD in ALL patients, inpatient mortality of the VOD patients, and VOD-related costs and hospital length of stay during the 100 days post-index period. Costs were sum of the plan paid amount and out-of-pocket amount in 2016 US dollars. Descriptive analyses were conducted for all VOD patients, severe VOD patients and non-severe VOD patients, respectively.
Results
A total of 2,571 ALL patients were identified and 3.4% of them had VOD. Severe VOD patients accounted for 52% of the VOD patients. All VOD patients had HSCT before the VOD event. VOD patients were younger (mean age: 44.2 vs. 50.1), more likely to be male (male: 62.5% vs 55.0%) but sicker (mean Charlson comorbidity index: 2.1 vs. 1.9) compared with the average ALL patients. Inpatient mortality was higher among severe VOD patients (37.0%) when compared to both non-severe VOD (14.3%) and average VOD patients (26.1%). Mean (SD) VOD-related costs were $55,975 ($160,335) for All VOD patients, $86,953 ($206,906) for severe VOD patients and $22,047 ($72,847) for non-severe VOD patients (Figure 1). Mean (SD) VOD-related length of stay was 39.3 (33.0) days among all VOD patients, 49.2 (36.8) days for severe VOD patients and 28.5 (24.3) days for non-severe VOD patients.
Conclusions
The incidence of VOD is low in adult B-cell ALL patients. The diagnosis of VOD is clinical and as such might be underdiagnosed within the current study. Approximately half of the VOD events among ALL patients are severe involving MOFs. VOD events are associated with considerable economic burden and high inpatient mortality, with greater economic burden and inpatient mortality rate among severe VOD patients. These results may potentially underestimate the burden of VOD in ALL patients due to the fact that the HCPCS code specific for defibrotide sodium was not available given its recent approval in the US (2016). Future studies with more recent data are needed to accurately quantify the economic burden of VOD in the US.
Zhang: Amgen Inc.: Employment, Equity Ownership. Romanov: Amgen, Inc.: Employment, Equity Ownership. Cong: Amgen Inc.: Employment, Equity Ownership.
