Skolnik, A.

Abstract Introduction:Hemophagocytic lymphohistiocytosis (HLH) is a severe hyperinflammatory syndrome characterized by excessive immune activation and cytokine release, leading to multi-organ failure and mortality. Despite guideline management to include chemotherapy and transplantation, the characteristics and predictors of critical outcomes in post-transplant-associated hemophagocytic lymphohistiocytosis (PT-HLH) remain poorly understood. Methods:This study is a retrospective cohort analysis of patients admitted to acute care hospitals in the U.S. with HLH between 2016 and 2018. We utilized the National Inpatient Sample, identifying HLH patients using International Classification of Diseases, Tenth Revision-Clinical Modification (ICD-10-CM) codes D76.1, D76.2, and D76.3. Patient demographics, such as age, gender, race, ethnicity, zip code, and insurance status, were obtained from the NIS, while hospital-level characteristics, location and teaching vs. non-teaching status, were considered in the study amongst others. We examined the baseline epidemiology of transplant status, including ICU-related outcomes and resource utilization in patients with and without transplants. Data were analyzed using STATA weighted function, with logistic regression for categorical outcomes. Results:Out of 8,330 adult HLH hospitalizations, 520 (6.2%) were transplant recipients. Among these, 350 (67%) had bone marrow transplants, 90 (17%) had kidney transplants, and 30 (5.8%) had liver transplants. The mean age of HLH patients was 50 ± 19 years; transplant patients were younger (mean age 46 ± 17 years) compared to non-transplant patients (50 ± 18 years), p<0.05. Transplant patients were more likely to be male (72.1% vs. 50.1%, p<0.05), have CMV infection (14.4% vs. 4.1%, p<0.05), be Hispanic (20.8% vs. 14.7%, p<0.05), come from higher median household income areas (38.8% vs. 24.5%, p<0.05), and be treated in teaching hospitals (96.1% vs. 85.8%, p<0.05). Among HLH patients who died in the hospital, 130 (25%) were transplant recipients, compared to 1,180 (15.1%) non-transplant recipients, p<0.05. After adjusting for potential confounders, transplant status was associated with a higher risk of mortality (adjusted odds ratio 1.77, 95% CI 1.11-2.83) and sepsis (adjusted odds ratio o1.78, 95% CI 1.08-2.92). Discussion:In examining a national cohort of PT-HLH cases, our findings review potential risk factors for critical care-related outcomes in post-transplant associated HLH care. PT-HLH patients in our cohort presented with distinct characteristics compared to non-transplant HLH cases. ICU-related outcomes showed statistically significant differences between transplant and non-transplant HLH patients. Specifically, transplant status remained independently associated with a higher risk of mortality and sepsis. Our findings underscore the importance of tailoring treatment plans to each patient's specific risk profile.