Anakinra versus etoposide-based therapy added to high-dose steroids for the treatment of secondary hemophagocytic lymphohistiocytosis.

OBJECTIVE: Hemophagocytic lymphohistiocytosis (HLH) is a rare life-threatening, hyperinflammatory syndrome usually treated with high-dose steroids (HDS), often complemented with adjunct therapies, such as etoposide (HLH-94 protocol). Anakinra has been reported to effectively treat HLH; however, has not been comparatively examined with etoposide-based therapies. We sought to evaluate the effectiveness and durability of these treatment approaches. METHODS: We performed a retrospective analysis of all adult patients diagnosed with secondary HLH between January 2011 and November 2022 who received anakinra and HDS, the HLH-94 protocol, HDS alone, or supportive care. RESULTS: Thirty adult patients with secondary HLH were included. Cumulative incidence (CI) of response at 30 days was 83.3%, 60%, and 36.4% for patients treated with anakinra, the HLH-94 protocol, and HDS alone, respectively. CI of relapse at 1 year was 50%, 33.3%, and 0% with the HLH-94 protocol, HDS, and anakinra and HDS, respectively. Overall survival at 1 year was higher with anakinra and HDS compared to the HLH-94 protocol, yet was not statistically significant (77.8% vs. 33.3%; hazard ratio: 0.29; p = .25). CONCLUSION: Treatment with anakinra and HDS in adults with secondary HLH was associated with higher response rates with longer survival compared with alternative therapies and should be further investigated in this setting.

A prediction model for acute kidney injury in adult patients with hemophagocytic lymphohistiocytosis.

Background and aims: Hemophagocytic lymphohistiocytosis is a clinical syndrome resulting from abnormally active immune cells and a cytokine storm, with the accompanying phagocytosis of blood cells. Patients with hemophagocytic lymphohistiocytosis often suffer acute kidney injury during hospitalization, which usually signifies poor prognosis. We would like to establish a prediction model for the occurrence of acute kidney injury in adult patients with hemophagocytic lymphohistiocytosis for risk stratification. Method: We extracted the electronic medical records of patients diagnosed with hemophagocytic lymphohistiocytosis during hospitalization from January 2009 to July 2019. The observation indicator is the occurrence of acute kidney injury within 28 days of hospitalization. LASSO regression was used to screen variables and modeling was performed by COX regression. Results: In the present study, 136 (22.7%) patients suffered from acute kidney injury within 28 days of hospitalization. The prediction model consisted of 11 variables, including vasopressor, mechanical ventilation, disseminated intravascular coagulation, admission heart rate, hemoglobin, baseline cystatin C, phosphorus, total bilirubin, lactic dehydrogenase, prothrombin time, and procalcitonin. The risk of acute kidney injury can be assessed by the sum of the scores of each parameter on the nomogram. For the development and validation groups, the area under the receiver operating characteristic curve was 0.760 and 0.820, and the C-index was 0.743 and 0.810, respectively. Conclusion: We performed a risk prediction model for the development of acute kidney injury in patients with hemophagocytic lymphohistiocytosis, which may help physicians to evaluate the risk of acute kidney injury and prevent its occurrence.

IFN-γ signature in the plasma proteome distinguishes pediatric hemophagocytic lymphohistiocytosis from sepsis and SIRS.

Hemophagocytic lymphohistiocytosis (HLH) is a syndrome characterized by pathologic immune activation in which prompt recognition and initiation of immune suppression is essential for survival. Children with HLH have many overlapping clinical features with critically ill children with sepsis and systemic inflammatory response syndrome (SIRS) in whom alternative therapies are indicated. To determine whether plasma biomarkers could differentiate HLH from other inflammatory conditions and to better define a core inflammatory signature of HLH, concentrations of inflammatory plasma proteins were compared in 40 patients with HLH to 47 pediatric patients with severe sepsis or SIRS. Fifteen of 135 analytes were significantly different in HLH plasma compared with SIRS/sepsis, including increased interferon-γ (IFN-γ)-regulated chemokines CXCL9, CXCL10, and CXCL11. Furthermore, a 2-analyte plasma protein classifier including CXCL9 and interleukin-6 was able to differentiate HLH from SIRS/sepsis. Gene expression in CD8+ T cells and activated monocytes from blood were also enriched for IFN-γ pathway signatures in peripheral blood cells from patients with HLH compared with SIRS/sepsis. This study identifies differential expression of inflammatory proteins as a diagnostic strategy to identify critically ill children with HLH, and comprehensive unbiased analysis of inflammatory plasma proteins and global gene expression demonstrates that IFN-γ signaling is uniquely elevated in HLH. In addition to demonstrating the ability of diagnostic criteria for HLH and sepsis or SIRS to identify groups with distinct inflammatory patterns, results from this study support the potential for prospective evaluation of inflammatory biomarkers to aid in diagnosis of and optimizing therapeutic strategies for children with distinctive hyperinflammatory syndromes.

Hemophagocytic syndrome: an unusual and underestimated complication of cytoreduction surgery with heated intraperitoneal oxaliplatin.

BACKGROUND: Hyperthermic intraperitoneal chemotherapy (HIPEC) improves the survival of select patients with peritoneal carcinomatosis. Hemophagocytic syndrome (HS) is a rare and potentially fatal disease. We describe our experience with five patients who developed HS following oxaliplatin HIPEC and propose a management procedure. METHODS: Hyperthermic intraperitoneal chemotherapy was performed using the open-abdomen technique (43 °C) with oxaliplatin (460 mg/m (2) ) for 30 min. If thrombocytopenia occurred from days 5 to 14, heparin-induced thrombocytopenia was evaluated. For thrombocytopenia with unknown etiology, we performed a bone marrow analysis (BMA). A BMA indicating HS stimulated an extensive infectious disease workup. Herein, we describe "reactive septic HS" and HS of unknown origin. RESULTS: We documented five patients with HS as a result of severe thrombocytopenia. Underlying infections were present in two patients who were treated with antibiotics and survived. For the remaining three patients, we found no underlying etiology of HS; multidisciplinary staff adapted the clinical management daily. Two patients died on postoperative days 40 and 29. The third patient survived after several operations and treatment with the VAC abdominal dressing system. CONCLUSIONS: We present these cases to ensure that physicians are aware of the symptoms of HS after HIPEC, which are important for initiating immediate life-saving therapy. This condition is a diagnostic and therapeutic emergency. When HS complicates HIPEC, aggressive, early medical, and surgical management is required. However, the optimal management has not been defined.

[Case of tuberculosis-associated hemophagocytic syndrome in a hemodialysis patient under steroid therapy].

A 70-year-old woman was referred and admitted to our hospital with fever of unknown etiology. She had a past medical history of pulmonary tuberculosis. Ten weeks before admission she was diagnosed with acute renal failure caused by crescentic glomerulonephritis. Oral steroid therapy was not effective and she required dialysis. On admission, she was started on empiric antibiotic treatment, with the suspicion of bacterial infection. On the 3rd hospital day, she developed sudden hypotension and underwent direct hemoperfusion with a polymyxin B immobilized fiber. Soon after, her blood pressure normalised. Her inflammatory level apparently then improved in terms of white blood cell count and C-reactive protein, although severe fatigue and liver dysfunction persisted. On the 17th hospital day, her blood pressure went down again, accompanied by progressive pancytopenia and significant increase in serum vitamin B12, lactate dehydrogenase and uric acid. The patient was transmitted to the intensive care unit where she received bone marrow aspiration. The result revealed marked hemophagocytosis. Suspecting lymphoma-associated hemophagocytic syndrome (HPS), we administered high-dose steroid and combination chemotherapy. The treatment had no effect, and the patient died on the 21st hospital day. The autopsy demonstrated a large number of tuberculous bacilli, marked hemophagocytosis and necrosis without granuloma formation in multiple organs, leading to the pathological diagnosis of tuberculosis-associated HPS. Tuberculosis in one of the major causes for morbidity and mortality in hemodialyzed patients. It often shows atypical clinical manifestation and is difficult to diagnose. HPS in general runs a mild course unless it is lymphoma or EB virus-associated. This case seemed like bacterial infection improved with antibiotics but turned out to be a rapidly progressive tuberculosis-associated HPS. A careful examination and extensive laboratory workup is necessary to rule out tuberculosis, particularly in patients undergoing hemodialysis.