Clinical Outcomes in Patients Admitted with Malignancy Associated Hemophagocytic Lymphohistiocytosis (HLH)

Background: Hemophagocytic Lymphohistiocytosis (HLH) is an aggressive and life threatening clinical syndrome that involves the rapid and excessive activation of the immune systems. It is associated with many conditions including infections, rheumatologic and autoimmune conditions, and drug-induced especially from chemotherapy. However, HLH associated with malignancy has especially poor outcomes. In this study we aim to investigate the clinical predictors of outcomes in patients who were admitted with malignancy associated HLH.

Methods: The National Inpatient Sample (NIS) was queried for all hospitalizations with a primary diagnosis of Hemophagocytic Lymphohistiocytosis from 2011 to 2017 using ICD-9-CM code 288.5 and ICD-10-CM code D 76.1. We looked at the most common malignancies associated with HLH. We also examined the most common comorbidities in this patient population. We analyzed the relation of different malignancies and co-morbidities with adverse outcomes, primarily the mortality rate. Data was analyzed using SPSS 27.0

Results: A total of 650 patients were identified during this studied time period who were admitted for malignancy associated with HLH. The mean age of this patient population was 52.41 years. Amongst these patients n=431 (66.7%) were males and the rest were females.

By far the most common malignancy associated with HLH included Lymphomas, which were present in n=483 (74.3%) patients. Non-Hodgkin's Lymphoma was much more common and present in n=431 (66.3%) patients, while Hodgkin's Lymphoma was present in n=56 (8.6%) of the patients. The other common malignancies included various leukemias n= 129 (19.8%), including AML n=35 (5.4%), ALL n=20 (3.1%), and CML n= 35 (5.4%), and solid tumors n=36 (5.4%), including lung cancer n=9 (1.4%) ,Breast Cancer n=9 (1.4%), and GI cancers n=10 (1.5%).

The most common comorbidities present in this HLH population included hypertension n=169 (26%), weight loss/malnutrition n=150 (23.5%), Kidney disease n=70 (10.8%), Diabetes n=97 (14.9%), heart failure n=55 (8.5%) liver disease n=72 (11.1%), rheumatologic disorders n=33 (5.1%) and obesity n=28 (4.3%).

The main patient outcome assessed was inpatient mortality. The overall inpatient mortality was 24.6 % in this patient population. In those patients who died, the odds of having bone and soft tissue cancer was the highest (odd ratio of 2.24). The odds ratio for other malignancies included AML (OR=2.12), Hodgkin's Lymphoma (OR=1.21), Multiple Myeloma (OR=1.20), CLL (OR=0.89), NHL (OR=0.79), Breast cancer (OR=0.3).

In those patient who died, the odds of having various comorbidities was the highest for liver disease (OR=2.7), alcohol abuse (OR=2.6), coagulopathy (OR=2.4), weight loss (OR=1.91), heart failure (OR=1.5), pulmonary disease (OR=1.31) and renal disease (OR=1.31).

Conclusion: HLH is an aggressive clinical syndrome that is rarely associated with various malignancies. Analysis of the National Inpatient Sample (NIS) data from hospital admissions in the United States shows that it is more common in males (66.7%). Despite advances in medical treatments the mortality is around 24.6%. By far the most common malignancy reported in this patient population is Non-Hodgkin's lymphoma that is present in (66.3%) of this patient population. Worse mortality rates were associated with patients who had underlying bone and soft tissue cancer, AML, Multiple Myeloma, and Hodgkin's lymphoma. Comorbidities including liver disease, alcohol abuse, coagulopathy, heart failure, and renal disease were also associated with worse mortality rates.