Purpose of Review This article summarizes the current state of knowledge of hairy cell leukemia (HCL) regarding presentation, diagnosis, therapy, and monitoring, including perspectives on emergent therapies. Recent Findings Over the past decade, there has been enormous progress in the understanding of the biology of HCL which has led to the development of novel therapeutic strategies. The maturation of data regarding existing management strategies has also lent considerable insight into therapeutic outcomes and prognosis of patients treated with chemo- or chemoimmunotherapy. Purine nucleoside analogs remain the cornerstone of treatment, and the addition of rituximab has deepened and prolonged responses in the upfront and relapsed setting. Targeted therapies now have a more defined role in the management of HCL, with BRAF inhibitors now having a potential in the first-line setting in selected cases as well as in relapse. Next-generation sequencing for the identification of targetable mutations, evaluation of measurable residual disease, and risk stratification continue to be areas of active investigation. Summary Recent advances in HCL have led to more effective therapeutics in the upfront and relapsed setting. Future efforts will focus on identifying patients with high-risk disease who require intensified regimens. Multicenter collaborations are the key to improving overall survival and quality of life in this rare disease.

Introduction: Neutropenic fever is a major cause of morbidity and mortality in all malignancies, especially acute leukemia. Protein energy malnutrition (PEM) is also a well-established risk factor for overall cancer related mortality. Acute myelogenous leukemia (AML) patients are frequently afflicted with neutropenic fever due to protracted neutropenia and community acquired, nosocomial, and opportunistic infections. They are also commonly malnourished due to poor oral intake, cachexia from underlying disease, and the toxicity of chemotherapy. To date, few studies have attempted to link neutropenic fever and PEM outcomes in AML. We thus aim to explore the prevalence and outcome of PEM in patients with AML and neutropenic fever. Methods: The Nationwide Inpatient Sample (NIS) database for 2016 and 2017 was searched for patients with primary discharge diagnosis of AML who had NF. This group was divided based on the presence or absence of PEM. The primary outcome was a comparison of inpatient mortality between the groups. Secondary outcomes included diagnosis of sepsis, mean total hospital charges (THC) and mean length of hospital stay (LOS). Outcomes were compared using multivariate regression analysis adjusting for sociodemographic and hospital characteristics and Charlson comorbidity index as a marker of severity. Results: A total of 10145 admissions met the inclusion criteria with AML and NF. Among the included patients, 1700 (16.7%) had PEM. Patient with PEM were significantly older (58.1 vs 55.2 years of age, p<0.001) but had no significant difference in sex (52.0 vs 55.0% females, p=0.308) and racial distribution, compared with patients without PEM. Overall, 825 (8.1%) hospitalizations had inpatient mortality. Patients with PEM had significantly higher adjusted odds ratio (aOR) of mortality (aOR: 2.00, 95% CI 1.335 - 2.998), developing sepsis (aOR: 2.06, 95% CI 1.514 - 2.812), as well as increase mean difference in LOS(8.6 days, 95% CI 5.77 - 11.37) and THC (105,600 USD 95% CI 57,000 - 154,000), compared to patients without PEM. Conclusion: PEM is associated with a significantly adverse outcome in patients with febrile neutropenia-- an almost double mortality rate and increased risk of complications like sepsis, increased LOS, and hospital costs. Neutropenic patients are markedly susceptible to fulminant systemic infections from various sources. PEM furthers this risk via weakening of host defenses including natural barriers and both innate and acquired immunity. Furthermore, in neutropenic patients with systemic infections, malnutrition may delay and impede wound healing along with immune responses which often contributes to a protracted course and adverse outcome. Nutrition in neutropenia has garnered limited attention, with some randomized trials showing limited to no benefit of the "neutropenic diet" in patients while depriving them of essential macro- and micronutrients. Nonetheless, current management guidelines for malnutrition in malignancies, particularly acute leukemias, are sparse. The profound impact of malnutrition in febrile neutropenia patients warrants further study, and we thus recommend further attention to screening practices and management strategies alongside primary treatment for malignancy and infection. Disclosures No relevant conflicts of interest to declare.

Introduction:HLH is a rare, life-threatening disorder, characterized by hyperstimulation of immune system leading to systemic inflammation and multi-organ failure. It is categorized as primary and secondary HLH. Secondary HLH usually affects adolescents and adults. It results from acquired immune dysregulation secondary to a number of etiologies, including infections, malignancy, and autoimmune diseases. Owing to less epidemiological data, adult HLH is thought to be underdiagnosed, making a true assessment difficult, however, some observational data suggest 40% of HLH cases occurs in adults. Disease presentation includes fever, cytopenias, organomegaly, liver function anomalies, elevated ferritin levels, and/or demonstration of macrophage activation in hematopoietic organs. In 2014, Fardet et al proposed the H-Score, a novel diagnostic score derived from 162 adult patients with HLH.We aim to report a retrospective review of Adult HLH in an urban safety-net hospital over the course of two decades along with predictive value of H-score in our patient population. Methods:We conducted a retrospective review of patients diagnosed with HLH at Cook County Health, Chicago between January 2000 and January 2019 after approval by the Institutional Review Board. Patients were identified from electronic records using ICD-10 codes D76.1, D76.2, and ICD-9 code 288.4. Patients under 18 years were excluded. MS excel was used for data collection and further descriptive statistics were calculated with frequencies and percentage. Results:After initial review, 12 confirmed and eligible cases were included in the study. Mean age at diagnosis of adult HLH at our center was 37, with male predominance(7 males, 4 females, and 1 female transgender). 5 were African-American, 6 were Hispanic, and 1 was Asian. Most common presentation was fever, seen in 10 out of 12 cases, along with variety of symptoms like fatigue, sore throat and jaundice.4 out of 12 patients (33%) had HIV/AIDS, with CD4 counts between 79 to 180. 3 were already receiving anti-retroviral therapy at the time of HLH diagnosis, while 1 was diagnosed with HIV/AIDS at the time of HLH diagnosis. Etiologic spectrum mainly included infectious (4 HIV and 3 EBV) and autoimmune (2 systemic lupus erythematous, 1 cold immune hemolytic anemia with immune thrombocytopenic purpura) causes. 1 patient had an underlying malignancy (diffuse large B-cell lymphoma). Etiology was not established in 1patient with no familial associations found in subsequent genetic evaluation. All patients had elevated liver enzymes. The mean ferritin level in our cohort was 19,198 ng/ml. Leucopenia was seen among most cases, 11 out of 12. The 1 patient noted to have a high white cell count was actually receiving corticosteroid therapy for cold immune hemolytic anemia. Most common bone marrow findings were hemophagocytosis (9 patients) and hypocellularity (7 patients). 2 had hypercelullar marrow and 1 had normal marrow. Genetic testing was performed in 4 patients; chromosomal abnormalities were not observed in any. Specific lab parameters in our cohort as included in HLH-2004 criteria is shown in Table 1. Calculated H scores in our cohort is shown in table 2. 11 patients fall under high probability for HLH. Conclusion:The most widely used diagnostic criteria for HLH is the HLH-2004 diagnostic criteria, derived from pediatric HLH study. It is often extrapolated for use in adults. There are several limitations to the HLH-2004 diagnostic criteria. sIL2r and NK function testing is not available in all centers, and many of the manifestations of HLH in adults are not included in the criteria. When using H score, a cutoff value of 169, corresponds to sensitivity of 93% and specificity of 86% in diagnosing HLH. In our study, 11 out of 12 patients (91.66) scored higher than 169, which is highly suggestive of HLH. The remaining 1 patient with H score of only 118, however, met the diagnosis of HLH by HLH-2004 criteria (score: 5/8). Therefore, although our study population was small, results of our study were in favor of using H-score as an appropriate diagnostic tool in adult-onset HLH, which also helps mitigate the restrictions of HLH-2004 criteria in adult population. Disclosures No relevant conflicts of interest to declare.