Case Of Hemophagocytic Lymphohistiocytosis Research Articles

Pre-diagnostic trajectory of pediatric hemophagocytic lymphohistiocytosis: observations from hematological and hepatic parameters.

Understanding the early features and characteristics of hemophagocytic lymphohistiocytosis (HLH) is essential for identifying high-risk individuals and also providing valuable pathological insights. This study aims to investigate the characteristics and trends of blood and hepatic parameters before an HLH diagnosis was established. Longitudinal hematological and hepatic test results from pediatric patients with HLH and an age- and sex-matched control group were analyzed. According to the length of time between hospital admission and the establishment of the HLH diagnosis, the HLH cases were divided into early-onset (≤ 7 days) and late-onset (> 7days) groups. Among the 229 pediatric HLH patients, the length of time between hospital admission and the establishment of an HLH diagnosis ranged from 0 to 41 days (median = 4 days). Over 80% of pediatric HLH patients presented abnormal laboratory results for aspartate aminotransferase (AST), triglycerides, lactate dehydrogenase (LDH), and hemoglobin at admission. The abnormal rates in the initial platelet count, neutrophil count, and fibrinogen tests were 67.3%, 48.3%, and 52.2%, respectively. The initial test results for AST, alanine aminotransferase (ALT), LDH, serum sodium, and albumin showed AUCs > 80% for discriminating early-onset HLH. For the discrimination of late-onset HLH, the performance of initial test results was poor. To conclude, abnormalities in AST, triglycerides, LDH, and hemoglobin are early presentations of pediatric HLH; platelet, neutrophil, and fibrinogen levels may become abnormal at a relatively late stage of the HLH disease trajectory; and the initial test results for AST, ALT, LDH, serum sodium, and albumin can be used to identify suspected early-onset HLH.

Diagnostic accuracy of bone marrow blood evaluation in haemophagocytic lymphohistiocytosis paediatric patients.

Haemophagocytic lymphohistiocytosis (HLH) is a rare and serious immunological syndrome that involves a strong activation of cytotoxic T lymphocytes and macrophages. HLH determines a cytokine-mediated tissue injury with a contemporary multi-organ failure and a high fatality rate. A retrospective study was performed considering the medical records of paediatric patients who underwent a bone marrow aspirate for suspect HLH. The biomarkers evaluated were among those included in the HLH-2004. Lactate dehydrogenase (LD) was also evaluated. Haemophagocytosis was evaluated in bone marrow blood smear slides. Enrolled were 11 patients included in the HLH group and 8 patients as controls. Haemoglobin and fibrinogen resulted lower in HLH patients than in controls, while blood triglycerides, serum ferritin and LD resulted increased. Blood triglycerides and fibrinogen discriminated HLH cases perfectly, with a sensitivity and specificity of 100%. Ferritin had a sensitivity of 100% and a specificity of 83% (cut off ≥3,721µg/L) and LD of 73% and of 100% (the cut off ≥1,903U/L). Haemoglobin was found to have a sensitivity of 75% and a specificity of 100% (cut off ≤ 96g/L). Total haemophagocytes cell counts were not different between patients and controls. Only the increased number of phagocytized nucleated red blood cells (NRBC) was found to be significantly increased in the patients. Erythrocytes phagocytosis (≥4/1,000 cells) only tended towards significance. The blood biomarkers showed better diagnostic performance than the morphological evaluation. Among the different cell lineages engulfed by haemophagocytes, the best diagnostic performance was obtained by phagocytosed mature erythrocytes and immature nucleated erythrocytes.

Hemophagocytic Lymphohistiocytosis (HLH): A Clinical and Pathological Grading System Based on the Presence of Hemophagocytosis

Abstract Introduction/Objective Hemophagocytic lymphohistiocytosis (HLH) is a heterogeneous group of disorders resulting from uncontrolled immune activation leading to severe hyperinflammation. The syndrome can be primary (genetic) or secondary to infections, malignancies, or autoimmune diseases. The diagnosis of HLH is challenging due to its nonspecific clinical presentation and the overlap with other conditions. This study aims to establish a reliable diagnostic approach for HLH by evaluating the accuracy of bone marrow histomorphological criteria in diagnosing the disease. Methods/Case Report We conducted a retrospective analysis of clinical and pathological data from patients diagnosed with HLH over a 12year period and included 38 patients with suspected HLH. A grading system for hemophagocytosis was developed based on the extent and frequency of hemophagocytic activity observed in bone marrow biopsies. Hemophagocytosis is categorized into four grades: Grade 0 indicates its absence, Grade 1 describes mild hemophagocytosis with less than 2 histiocytes containing hemophagocytosis per slide, Grade 2 denotes moderate hemophagocytosis with 3 to 5 histiocytes per slide, and Grade 3 signifies severe hemophagocytosis with more than 5 histiocytes per slide. Clinical data, comprising laboratory parameters and treatment outcomes, were analyzed in relation to the histologic grading of hemophagocytosis. Results (if a Case Study enter NA) Among the cases, grade 1 had 1 resolved case, 4 cases meeting 2 criteria all resolved, and 13 cases meeting 4 or more criteria resulted in 5 deaths and 8 resolutions. Grade 2 included 10 cases, with 2 meeting 2 criteria and resolving, and 8 meeting 4 or more criteria resulting in 5 deaths and 3 resolutions. Grade 3 comprised 10 cases, with 3 meeting 3 criteria and resolving, 3 meeting 5 or 7 criteria resulting in 1 death and 2 resolutions each, and 4 meeting 6 or 8 criteria resulting in 2 deaths and 2 resolutions each. Conclusion In our retrospective analysis of bone marrow biopsies from 38 patients with suspected HLH, our results indicate that the presence and extent of hemophagocytosis strongly suggest HLH. Implementing these criteria significantly improved diagnostic accuracy, reducing misdiagnosis rates and enabling timely therapy initiation. This study underscores the value of bone marrow histomorphological criteria in diagnosing HLH and stresses their importance in the standard diagnostic process for suspected HLH cases.

The Ticking Time Bomb: A Case of Hemophagocytic Lymphohistiocytosis Triggered by Ehrlichiosis in a Kidney Transplant Recipient

The Ticking Time Bomb: A Case of Hemophagocytic Lymphohistiocytosis Triggered by Ehrlichiosis in a Kidney Transplant Recipient

From Diagnosis to Treatment: A Successful Case of Haemophagocytic Lymphohistiocytosis of Presumed Bacterial Aetiology in an Adult.

Haemophagocytic lymphohistiocytosis is characterised as a rare inflammatory syndrome that occurs due to uncontrolled systemic immune activation.Timely diagnosis and treatment are essential, as mortality is still high.

Visceral leishmaniasis complicated with hemophagocytic lymphohistiocytosis and resistant to amphotericin B: a case report

IntroductionHemophagocytic lymphohistiocytosis characterized by hemophagocytosis leading to uncontrolled inflammation; the most common etiology in secondary cases of hemophagocytic lymphohistiocytosis is viral infections, especially Epstein–Barr virus. Visceral leishmaniasis is a vectorborne protozoal disease caused by Leishmania donovani complex. It is common in tropical and subtropical regions, with 50,000–90,000 new cases annually.Case presentationA 15-month-old Arab female was admitted to our hospital with 15 days of fever and decreased weight. On clinical examination, she had a markedly enlarged liver and spleen that were palpable 4 cm and 6 cm below the costal margin, respectively. The peripheral blood smear showed hypochromic microcytic anemia, poikilocytosis, reactive lymphocytosis, and mild thrombocytopenia. Bone marrow aspiration did not show malignancy or any other pathological findings. The patient was put on antibiotic therapy without improvement. Repeated bone marrow aspiration showed erythrophagocytosis; intracellular small round organisms looked like the amastigote form of Leishmania (Donovan bodies) with no evidence of malignancies. Her lab values showed ferritin greater than 500 ug/L, pancytopenia, and hypertriglyceridemia. The patient was diagnosed with hemophagocytic lymphohistiocytosis secondary to visceral leishmaniasis.ConclusionHemophagocytic lymphohistiocytosis secondary to visceral leishmaniasis is an extensively rare phenomenon in the medical literature that causes challenges in diagnosis and management. Steroids should be used wisely to not cover the symptoms of infections or malignancy, and amphotericin B resistance should be kept in mind in unresponsive Leishmania cases.

Predicting relapsed/refractory disease in childhood hemophagocytic lymphohistiocytosis based on clinical features at diagnosis: A 13-year single-institute retrospective study in Thailand.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disease. Relapsed/refractory disease is the main cause of death. This study aims to determine the prognostic indicators for relapsed/refractory disease in childhood HLH (R/R HLH). Infants and children under 18 years of age who were diagnosed with HLH according to HLH-2004 criteria, MAS-HLH criteria for rheumatologic diseases, or H-score undergoing treatment in Chiang Mai University hospital between 2010 and 2022 were included. Demographic data, clinical characteristics, and laboratory parameters were retrospectively reviewed. Out of 86 childhood HLH cases, 30 patients (34.9%) experienced R/R HLH. All patients with primary HLH developed R/R HLH. The most common form of secondary HLH was infection-associated hemophagocytic syndrome (IAHS), comprising 43 cases. Of these, 37.2% had relapsed or refractory disease. Univariable analysis identified several potential risk factors for R/R HLH, including younger age, severe disease status, higher HLH-2004 criteria scores, higher H-scores, overt DIC, higher pSOFA scores, and increased levels of aspartate aminotransferase, total bilirubin, and direct bilirubin. Multivariable logistic regression analysis revealed that a pSOFA score of ≥ 8 and age < 3 years were independent risk factors for R/R HLH, with adjusted odds ratios of 6.35 (95% confidence interval [CI], 1.18-34.19; P = 0.032) and 3.62 (95% CI, 1.04-12.63; P = 0.044), respectively. Children with HLH who have a pSOFA score of ≥ 8, or are younger than 3 years, are at a higher risk of relapsed or refractory disease. Further evaluation of management strategies in this context is warranted.

A fatal case of hemophagocytic lymphohistiocytosis in an elderly male

We present a case of an 87-year-old male with hemophagocytic lymphohistiocytosis (HLH). Hemophagocytic lymphohistiocytosis is a life-threatening disorder characterized by dysregulated immune activity leading to end-organ damage. Hematologic malignancies appear to be the main cause of secondary HLH. Diagnostic criteria include fever, cytopenia, splenomegaly, hypertriglyceridemia, hypofibrinogenemia, a ferritin level greater than 500 ng/mL, low NK-cell activity, and elevated sIL2Ra levels greater than or equal to 2400 U/mL. Five out of eight of the criteria are necessary to establish a diagnosis of HLH. Our patient met five out of eight diagnostic criteria for HLH (fever, cytopenia, splenomegaly, hypertriglyceridemia, and ferritin level greater than 500 ng/mL). Bone marrow aspirate revealed hemophagocytosis. Bone marrow biopsy revealed marginal zone B cell lymphoma, which is presumed to be the underlying cause of his condition. Due to poor functional status, the patient was a poor candidate for curative treatment, and the family chose not to pursue this route. The patient was treated with Decadron 20 mg intravenous (IV) push daily until he ultimately died, likely due to respiratory failure due to heart failure (HF).

Outcome and Prognostic Factors of Hemophagocytic Lymphohistiocytosis in Children: Experience From a Low- and Middle-Income Country.

Objective Hemophagocyticlymphohistiocytosis (HLH) is a life-threatening condition especially in low- and middle-income countries (LMICs). This study was done to evaluate the outcome and prognostic factors of HLH in patients presenting to our center. Methods The study was carried out at the Paediatric Oncology Department of Combined Military Hospital (CMH) in Rawalpindi, Pakistan. All cases of HLH, from one month to 15 years of age enrolled between January 1, 2013 to June 30, 2023, were included. IBM SPSS Statistics for Windows, version 25.0 (released 2017, IBM Corp., Armonk, NY) was used for statistical analysis, and t-test and chi-square tests were used for comparison between continuous and categorical variables. Frequencies and percentages were calculated for categorical variables. Results Out of 115 patients, seven (6%) abandoned the treatment. The data of 108 cases, including 58 males (53.7%), were analyzed. The mean age at diagnosis was 31.5 ± 39.03 months. The mean time to reach a pediatric oncologist was 30.20 ± 22.15 days. Fever and pallor were common symptoms occurring in 107 (99.1%) and 98 (90.7%) cases, respectively. Jaundice was present in 44 (40.7%), visceromegaly in 64 (59.3%), and bruising/bleeding in 16 cases (14.8%). Twenty-six (24.1%) patients underwent hematopoietic stem cell transplant (HSCT), out of which 17 (65.4%) children were cured. Overall survival at two years, five years, and 10 years was 38%, 37%, and 36.1%, respectively. Disease-free survival at two years, five years, and 10 years was 33.3%, 32.4%, and 31.5%, respectively. Conclusion HLH leads to high mortality due to delayed or misdiagnosis in LMICs. Early diagnosis and early referral to a pediatric oncologist is the detrimental factor in survival for HLH. HSCT is the treatment of choice for primary, refractory, or relapse cases.

Hemophagocytic Lymphohistiocytosis: A Case Series From a Tertiary State Hospital in Malaysia and a Review of Current Literature.

Hemophagocytic lymphohistiocytosis (HLH) is a lethal emergency. Delaysin diagnosis and treatment are detrimental to the health of patients. Classical clinical manifestations of HLH include fever, cytopenia, liver dysfunction, central nervous system involvement, and coagulopathy. We report seven cases of secondary HLH in adults diagnosed from a total of 1200 bone marrow aspiration and trephine biopsy (BMAT) examinations in our center, with various presentations and underlying triggers including infection, malignancy, and autoimmune disease. HLH can present with non-specific signs and symptoms. Early recognition of HLH is crucial to enable the commencement of therapy as early as possible to prevent mortality resulting from multi-organ failure.

INFECTIOUS DISEASES COMPLICATED BY HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS – A RARE CASE SERIES

Hemophagocytic lymphohistiocytosis (HLH) is a rare, yet potentially fatal disorder of uncontrolled inflammation and dysregulated immunity. Patients may present with features ranging from fever, rash, and cytopenias to fatal multiorgan failure. Here, we present a case series reporting four cases of HLH, their clinicopathological findings, laboratory investigations, and outcomes. The underlying causes for the four cases were found to be infective ones, i.e., Leptospira, hepatitis-E and herpes simplex virus-1, kala-azar and malaria and enteric fever. HLH is a manifestation of the dysregulated immune response of various T cells leading to cytokinemia causing an accumulation of macrophages and T lymphocytes in various tissues. Infections account for about half of all HLH cases in adults the world over. In our institute, infections may still be more prevalent as a cause. Moreover, this may be the scenario in our country where infectious diseases remain a major proportion of the disease burden.

57 A Unique Case of Hemophagocytic Lymphohistiocytosis a Complication of Peritoneal Dialysis Associated Peritonitis in a Patient with Miliary Tuberculosis

57 A Unique Case of Hemophagocytic Lymphohistiocytosis a Complication of Peritoneal Dialysis Associated Peritonitis in a Patient with Miliary Tuberculosis

Diagnostic Challenges in Hemophagocytic Lymphohistiocytosis, a Rare, Potentially Fatal Disease: Two Case Studies.

Hemophagocytic lymphohistiocytosis (HLH) is a rare, and potentially fatal, syndrome, characterized by immune system dysregulation, with excessive activation of the macrophages and cytotoxic T cells. It can be classified into primary (genetic) and secondary (acquired) forms. HLH presents with fever, hepatosplenomegaly, cytopenia, and hyperferritinemia, with involvement of various organs. The initial symptoms of HLH are non-specific, but as, if untreated, it can progress rapidly to multiorgan failure, timely diagnosis is essential. We present here two cases of HLH in infants that illustrate the importance of early diagnosis and appropriate treatment, along with a short review of HLH.

Hemophagocytic Lymphohistiocytosis (HLH) in Patients with Tick-Borne Illness: A Scoping Review of 98 Cases.

Hemophagocytic lymphohistiocytosis (HLH) secondary to tick-borne infections is a rare but potentially life-threatening syndrome. We performed a scoping review according to PRISMA guidelines to systematically analyze the existing literature on the topic. A total of 98 patients were included, with a mean age of 43.7 years, of which 64% were men. Most cases, 31%, were reported from the USA. Immunosuppression was present in 21.4%, with the most common cause being previous solid organ transplantation. Constitutional symptoms were the most common, observed in 83.7% of the patients, while fever was reported in 70.4% of cases. Sepsis was present in 27.6%. The most common laboratory abnormalities in this cohort were thrombocytopenia in 81.6% of patients, while anemia, leukopenia, and leukocytosis were observed in 75.5%, 55.1%, and 10.2%, respectively. Liver enzyme elevation was noted in 63.3% of cases. The H-score was analyzed in 64 patients, with the mean value being 209, and bone marrow analysis was performed in 61.2% of patients. Ehrlichia spp. was the main isolated agent associated with HLH in 45.9%, followed by Rickettsia spp. in 14.3% and Anaplasma phagocytophilum in 12.2%. Notably, no patient with Powassan virus infection or Lyme borreliosis developed HLH. The most common complications were acute kidney injury (AKI) in 35.7% of patients, shock with multiple organ dysfunction in 22.5%, encephalopathy/seizure in 20.4%, respiratory failure in 16.3%, and cardiac complications in 7.1% of patients. Treatment included antibiotic therapy alone in 43.9%, while 5.1% of patients were treated with immunosuppressants alone. Treatment with both antibiotics and immunosuppressants was used in 51% of patients. Appropriate empiric antibiotics were used in 62.2%. In 43.9% of cases of HLH due to tick-borne disease, patients received only antimicrobial therapy, and 88.4% of those recovered completely without the need for immunosuppressive therapy. The mortality rate in our review was 16.3%, and patients who received inappropriate or delayed empiric therapy had a worse outcome. Hence, we suggest empiric antibiotic treatment in patients who are suspected of having HLH due to tick-borne disease or in whom diagnostic uncertainty persists due to diagnostic delay in order to minimize mortality.

HLH in a patient with post-surgical Ebstein’s anomaly: Case report

This case was interesting as it presents a rare complication in a rare congenital anomaly. We present it to raise awareness about serious fatal complications that could occur in a CHD postoperative patient which may not be related to their surgery. The heart surgery was successful but the patient passed away from complications which arose postoperatively. A 34-year-old male with Ebstein’s anomaly and severe tricuspid regurgitation status post ASD closure, atrialized ventricular plication and tricuspid annuloplasty at 6 years old presented with symptoms of congestive heart failure. He underwent tricuspid valve replacement and insertion of epicardial dual chamber pacemaker. Patient developed recurrent high fevers on the first night following surgery that were unresponsive to antibiotics and antipyretics. Evaluation revealed hyperferritinemia, thrombocytopenia, anemia and splenomegaly consistent with Hemophagocytic Lymphohistiocytosis (HLH). EVB titers were found to be elevated as a possible inciting infection. He was treated with Dexamethasone, Etoposide and Cyclopsorine, however he developed Heparin Induced Thrombocytopenia (HIT) followed by Disseminated Intravascular Coagulopathy (DIC) and died from a presumed pulmonary embolism. Conclusion: Surgical intervention outcomes in complex congenital heart disease patients can be complicated by infectious and hematological complications. If more cases of cardiac bypass related HLH are identified, the presence or absence of cold agglutinins as a factor should be studied. Timely recognition will prevent unnecessary mortality and morbidity.

Hemophagocytic lymphohistiocytosis following pembrolizumab and bevacizumab combination therapy for cervical cancer: a case report and systematic review

BackgroundProgrammed cell death protein 1 (PD-1) checkpoint inhibitors such as pembrolizumab are novel therapeutics used to treat various advanced malignancies. Immune-related adverse events are common, among the most serious of these toxicities is hemophagocytic lymphohistiocytosis (HLH), which is a life-threatening disorder of unbridled immune activation but has not been properly established.MethodsWe have procured the first case of hemophagocytic lymphohistiocytosis as an aftermath of treatment with pembrolizumab from the Sir Run Run Shaw Hospital, Zhejiang University, China. In a pursuit to enhance the understanding of this condition, a comprehensive systematic review was performed encompassing all reported instances of ICI-associated Hemophagocytic lymphohistiocytosis within the realms of PubMed and Embase databases.ResultsWe detail the recovery of a cervical cancer patient with a history of psoriasis who developed HLH after combined pembrolizumab and bevacizumab treatment. Remarkably, tumor lesions exhibited substantial and sustained regression. From an analysis of 52 identified Immune Checkpoint Inhibitor (ICI)-related HLH cases, we discovered that HLH often occurred within the first two treatment cycles and approximately 20% of these patients had a history of autoimmune-related diseases. Despite a 15% mortality rate, the majority of patients experienced positive outcomes. Notably, in instances of recovery from HLH, 80% showed positive tumor outcomes. Even after discontinuation of ICI treatment, tumor control persisted in some cases.ConclusionWe identified the first case of HLH caused by ICI treatment in cervical cancer and summarized the possible occurrence factors of these cases, the treatment outcomes of HLH, and the impact on tumor outcomes.

Unique presentation of T-cell/histiocyte-rich large B cell lymphoma complicated with hemophagocytic lymphohistiocytosis: Case report and review of the literature.

Hemophagocytic lymphohistiocytosis (HLH) is a rare, lifethreatening hyperinflammatory disorder characterized by dysfunction of NK cells and cytotoxic lymphocytes. We present a rare case of a patient diagnosed with HLH who presented with persistent fever during treatment for refractory T-cell/histiocyte-rich large B-cell lymphoma (TCHRLBCL), highlighting the challenges of managing HLH in the context of refractory lymphoma. According to our review of the literature, this is the first case of HLH that developed several months into treatment for refractory TCHRLBCL and not in close temporal relation to lymphoma diagnosis.

Zoonotic Bacterial Infections Triggering Cytokine Storm Syndrome.

Zoonotic infections can result in life-threatening complications that can manifest with hemophagocytic lymphohistiocytosis (HLH)/cytokine storm syndrome (CSS). Bacteria constitute the largest group of zoonotic infection-related HLH cases. The growing list of zoonotic bacterial infections associated with HLH/CSS include Brucella spp., Rickettsia spp., Ehrlichia, Coxiella burnetii, Mycobacterium spp., and Bartonella spp. Patients most commonly present with fever, cytopenias, hepatosplenomegaly, myalgias, and less frequently with rash, jaundice, and lymphadenopathy.

Hemophagocytic Lymphohistiocytosis (HLH) in a Post-COVID-19 Infection: A Case Report

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyper inflammatory process caused by extensive immune activation and characterized by multi organ dysfunction. During COVID-19 pandemic secondary hemophagocytic lymphohistiocytosis has been reported in acute phase of COVID-19 infection, but HLH in recovered post-COVID-19 patients is rare. We report a case of HLH following of COVID infection. Case Description: 72-year-old female with well-controlled rheumatoid arthritis and COVID infection 2 months prior presented with progressive shortness of breath. She was diagnosed with acute on chronic heart failure, acute kidney injury, worsening anemia and thrombocytopenia. She progressively got worse during hospitalization and on day 9 developed fever and multiorgan failure (pancytopenia, acute liver injury, respiratory failure requiring mechanical ventilation, renal failure requiring hemodialysis). Labs included hemoglobin of 7.9 g/dL, platelets 50 Th/uL, ANC 1.38 Th/uL, LDH 6000 IU/L, ferritin &amp;gt;10,000 ng/ml, fibrinogen 136 mg/dL, triglycerides 656 mg/dL. HLH was suspected and a bone marrow biopsy showed occasional macrophages with hemophagocytosis without evidence of lymphoproliferative disorder (Figure 1). Interleukin-2 receptor soluble was elevated at 57026.9 pg/mL. HLH diagnosis was established, and patient was started on HLH-94 protocol with etoposide and dexamethasone. She improved quickly with treatment and was extubated in a few days. After 4 weeks, there was continued clinical improvement with improving liver function, LDH was down to 373, ferritin 3586 but she remained cytopenic needing transfusion support. By week 6, she was off dialysis and repeat Interleukin-2 receptor soluble was 2500 pg/ml and ferritin was 2500 ng/ml. A positron emission tomography (PET) scan did not show any evidence of lymphoma. Patient was not considered to be suitable candidate for stem cell transplant and was monitored. Within 6-8 weeks, she was noted to have worsening LDH, ferritin, liver function and patient was started on ruxolitinib 5 mg twice a day and dexamethasone 2 mg daily. Patient continued to have worsening anemia, thrombocytopenia, LDH and ferritin. Patient was readmitted around week 6 of ruxolitinib treatment with progressive shortness of breath. Patient was re-treated with dexamethasone and etoposide. On day 10 of 2nd hospitalization, she developed acute respiratory failure needing mechanical ventilation and was diagnosed with abdominal viscus perforation. After discussion with family, she was transitioned to best supportive care given poor prognosis. Discussion: Few cases of HLH in post-covid-19 patients have been reported in the literature, but this entity may be likely under diagnosed given the delayed presentation, absence of definitive clinical, laboratory, or histopathological criteria. Immune dysregulation and macrophage activation due to subclinical inflammation following post-COVID-19 infection is postulated to underlie the pathogenesis of HLH in post-COVID-19 patients. The hyperinflammatory situation results in multi-organ failure and high mortality rates. The HLH2004 has been recommended as the diagnostic criteria of choice for HLH among post-COVID-19 patients. Immunosuppressive therapies with steroids, and etoposide are the conventional first-line agents based on the HLH94 protocol; however, refractory cases have been shown to respond to other immunosuppressive agents and biologics including ruxolitinib, alemtuzumab, and emapalumab. Figure 1: A. Hemophagocytosis (Macrophage ingesting lymphocyte) B. Hemophagocytosis, more specifically-erythrophagocytosis (macrophage ingesting red blood cell).

Differences in Diagnostic Characteristics and Outcomes in Adults with Malignancy-Associated and Non-Malignancy-Associated Hemophagocytic Lymphohistiocytosis (HLH)

Introduction: Hemophagocytic lymphohistiocytosis (HLH) is a rare syndrome characterized by life-threatening inflammation. In adults, roughly 50% of HLH manifests in association with an underlying malignancy (most commonly lymphoma), and the remaining cases are due to infection, autoimmune disease, late presentations of genetically-driven HLH, and sometimes multifactorial or idiopathic causes. Although the majority of prospective data for HLH are derived from children, survival outcomes for non-malignant causes of adult HLH (nmHLH) are thought to rival pediatric HLH; however, outcomes for malignancy-associated HLH (mHLH) appear to be substantially worse (~10-30% 5-year overall survival) in the literature. As diagnostic and prognostic models for HLH outcomes have primarily been constructed using pediatric data, attempts have been made to develop diagnostic indices applicable to adult HLH (particularly mHLH). Here, we summarize the clinical and laboratory characteristics of mHLH and nmHLH in a retrospective observational study, and evaluate the role for common diagnostic tools for adult HLH. Methods: Patients &amp;gt;18 years old, fulfilling at least five of the HLH-2004 diagnostic criteria with at least 3 months of follow-up (among survivors) were enrolled. All included patients received definitive HLH therapy, including cancer-directed therapy when appropriate, but those receiving only systemic steroids were excluded. Treatment-related HLH, such as HLH occurring with immune effector cell therapy or hematopoietic cell transplantation, was excluded. Clinical and laboratory parameters reflect the most recent values on or prior to diagnosis and treatment initiation. Differences between mHLH and nmHLH were assessed with two-tailed t-test or Wilcoxon test. Survival outcomes are estimated by Kaplan-Meier. Multivariate analysis was performed using Cox proportional hazards and compared using logrank test. Results: 42 adults were diagnosed with HLH requiring HLH-specific therapy (23 mHLH, 19 nmHLH) between 3/2016 and 3/2023 with a median age of 50 (range 21-75). Of the mHLH cases, 44% were due to T/NK cell lymphomas; 52% were B cell lymphomas including 26% Hodgkin. Of the nmHLH cases, most were due to infection (47%); while others were deemed to be idiopathic (26%) or genetic (16%). All patients with mHLH had fever (v 84% in nmHLH); 91% met cytopenia criteria (v 68%), and absolute neutrophil count (ANC), hemoglobin (Hgb), and platelet count (plt) were all statistically lower than in nmHLH (mean ANC 3.2 v 11.3; Hgb 7.8 v 8.5; plt 43 v 88; p&amp;lt;0.05). Mean soluble interleukin-2 (sIL2) level was significantly higher in mHLH (39,579 pg/mL v 18,484) after adjusting for a single outlier. All other HLH-2004 diagnostic parameters were not statistically different between mHLH and nmHLH, including ferritin and sIL2/ferritin index. All mHLH patients had an underlying lymphoma and met the optimized HLH inflammatory (OHI) index except a single patient with leukemia; 4 patients with nmHLH did not meet the OHI index. In 79% of patients, the HLH94 regimen was incorporated in the induction regimen; the remaining utilized chemotherapy or antibiotics, with and without adjunctive steroids. 4 cases proceeded to allogeneic transplantation. Relapse rates were high, with median relapse-free survival (RFS) being 37 days (23 v 47 days for mHLH and nmHLH, respectively); median overall survival (OS) was 96 days (86 v 149 days). RFS/OS was not statistically different between mHLH and nmHLH. Age was a significant predictor of OS but not RFS; no other diagnostic parameter was predictive, including degree of ferritin or sIL2 elevation. 13 patients were alive at the time of last follow-up (6 mHLH, 7 nmHLH). Conclusions: In this single center retrospective study, both mHLH and nmHLH requiring HLH-directed therapy demonstrated poor survival outcomes in adults. The degree of cytopenias and sIL2 elevation were more significant in mHLH in comparison with nmHLH. The OHI index identified all cases of lymphoma-associated HLH but neither ferritin nor sIL2 levels were predictive of survival. These data emphasize the need for therapeutic advances for management of adults with mHLH and nmHLH and continued optimization of diagnostic criteria for adult HLH.