Longer Hospitalizations, Increased Inpatient Mortality and Costs Are Associated with Alloimmunization Among Patients with Myelodysplastic Syndromes
Authors: Gehrie Eric , Viayna Elisabet , Blanchette Christopher , Meny Geralyn , Noumsi Ghislain , Huber Maria , Runken M. Chris 
Published: November 2021

Abstract
Red Blood Cell (RBC) transfusions remain an important part of the management of anemia caused by myelodysplastic syndromes (MDS). Almost 90% of patients diagnosed with MDS require at least one RBC transfusion and 30%-45% require chronic transfusions (Singhal Haematologica. 2017;102(12):2021-2029). Importantly, it is estimated that 11% of MDS patients form alloantibodies as a result of RBC transfusions. Despite this relatively high alloimmunization rate, MDS patients are almost never prophylactically transfused with RBCs from antigen-matched donors, a strategy which has been shown to reduce the incidence of alloimmunization among patients with sickle cell disease, but which also increases costs and utilizes a limited resource (antigen negative RBCs). Herein, we present the economic and clinical burden of RBC alloimmunization in MDS patients, in order to better inform decision making regarding prophylactic RBC antigen matching.
A cross-sectional study using the Premier Hospital chargemaster dataset was performed. All outpatient and inpatient discharges from January 2015 to June 2019 were included. MDS was defined using ICD-10 code D.46. Because there is no diagnosis code for alloimmunization, alloimmunized patients were identified based on the presence of antiglobulin crossmatch (CXM) and RBC antibody identification (RAI) codes in Premier records. This approach was validated by comparing the published rate of alloimmunization observed in patients diagnosed with MDS as well as hereditary hemorrhagic telangiectasia (HHT; another population with a relatively high alloimmunization rate) to the prevalence of both CXM and RAI codes in the Premier dataset during 2018. The comparison showed that our approach successfully modeled the published alloimmunization rates in HHT (16.8% vs 15.3%) and MDS (11.5% vs 11%) (Zheng Transfusion. 2018;58(3):775-780, Singhal Haematologica. 2017;102(12):2021-2029).
Demographic, clinical, and billing characteristics were gathered. Total cost per discharge, hospital and intensive care unit (ICU) length of stay, and inpatient mortality, were calculated for both study groups and compared. Bivariate comparisons were performed, assuming a two-tailed test of significance and an α level of 0.05. Multivariable regression models adjusting for sex, age, admission date, visit type (outpatient vs. inpatient) type of MDS based on the World Health Organization (WHO) classification and diagnosis-related groups (DRG) with an incidence ≥1% of inpatient visits were performed.
Overall, 179,819 MDS patient encounters were identified. Of these, 11,948 were alloimmunized and 167,871 were not alloimmunized (Table 1). When assessing incremental economic and clinical outcomes for the alloimmunized MDS population, multivariate models showed that alloimmunization led to significantly worse economic and clinical outcomes through all variables assessed (Table 2). The incremental median cost per inpatient and outpatient visit for the alloimmunized population were $2,829 (p&lt;0.0001) and $630 (p&lt;0.0001) higher, respectively. Alloimmunized patients had significantly longer inpatient hospitalizations (7.2 vs 8.2 days; p&lt;0.0001) as well as longer ICU stays (4.4 vs 6.8 days; p&lt;0.0001). Alloimmunized)A patients also encountered a 38% increased risk of being admitted to intensive care, and a 30% higher risk of inpatient mortality.
This analysis discloses that alloimmunization is associated with higher healthcare costs and worsened clinical outcomes in the MDS population. Further work is needed to clarify whether alloimmunization is causally related to these outcomes, or whether alloimmunization is incidentally more common among patients with worse disease. The present study was not designed to assess the effectiveness of prophylactic antigen matching in the prevention of alloimmunization in the transfused MDS population, and further work is needed to confirm the findings presented herein. However, decisions regarding provision of antigen-matched RBCs to MDS patients should consider the potential for downstream consequences of alloimmunization.
Figure 1 Figure 1.

Disclosures
Gehrie: Grifols SSNA: Consultancy, Honoraria. Viayna: Grifols S.A.: Current Employment. Blanchette: Grifols SSNA: Consultancy; Novo Nordisk Inc.: Current Employment. Meny: Grifols SSNA: Current Employment. Noumsi: Grifols SSNA: Current Employment. Huber: Grifols SSNA: Current Employment. Runken: Grifols SSNA: Current Employment.