Recommendations for the management of hemophagocytic lymphohistiocytosis in adults

Abstract

Hemophagocytic lymphohistiocytosis (HLH) is a severe hyperinflammatory syndrome induced by aberrantly activated macrophages and cytotoxic T cells. The primary (genetic) form, caused by mutations affecting lymphocyte cytotoxicity and immune regulation, is most common in children, whereas the secondary (acquired) form is most frequent in adults. Secondary HLH is commonly triggered by infections or malignancies but may also be induced by autoinflammatory/autoimmune disorders, in which case it is called macrophage activation syndrome (MAS; or MAS-HLH). Most information on the diagnosis and treatment of HLH comes from the pediatric literature. Although helpful in some adult cases, this raises several challenges. For example, the HLH-2004 diagnostic criteria developed for children are commonly applied but are not validated for adults. Another challenge in HLH diagnosis is that patients may present with a phenotype indistinguishable from sepsis or multiple organ dysfunction syndrome. Treatment algorithms targeting hyperinflammation are frequently based on pediatric protocols, such as HLH-94 and HLH-2004, which may result in overtreatment and unnecessary toxicity in adults. Therefore, dose reductions, individualized tailoring of treatment duration, and an age-dependent modified diagnostic approach are to be considered. Here, we present expert opinions derived from an interdisciplinary working group on adult HLH, sponsored by the Histiocyte Society, to facilitate knowledge transfer between physicians caring for pediatric and adult patients with HLH, with the aim to improve the outcome for adult patients affected by HLH.

Diagnostic challenges for a novel SH2D1A mutation associated with X‐linked lymphoproliferative disease

“…Confirming the presence of hemophagocytosis, autopsy also revealed EBV‐associated T‐cell lymphoma in spleen, bone marrow, and lymph nodes. Although recommended, a molecular basis of lymphoma was not established. No family history of EBV‐HLH was reported.…”

Reevaluating the role of ferritin in the diagnosis of adult secondary hemophagocytic lymphohistiocytosis

“…In spite of the above data however, an expert working group on adult HLH from the Histiocyte Society recently published guidelines reaffirming the role of the HLH‐94 criteria (including the ferritin cutoff of 500 ng/mL) as the standard diagnostic tool for adult HLH . Some newer diagnostic tools for adult HLH have been emerging in recent years, most notably the H‐score .…”

“…However, extreme elevations in serum ferritin in the setting of critical illness continue to prompt strong consideration of HLH among clinicians, often precipitating intense concern and invasive testing . Furthermore, recent guidelines issued by an expert panel reinforce the HLH‐2004 criteria in their current form (including the ferritin criterion) as the gold standard for the diagnosis of adult secondary HLH . This suggests that additional data are needed to clarify the role of ferritin in the evaluation of adult secondary HLH and spur change in how clinicians diagnose secondary HLH among adults.…”

Clinical diagnosis and treatment recommendations for immune checkpoint inhibitor‐related hematological adverse events

“…The clinical manifestations are nonspecific, which share many similarities with severe infections and tumor progression. Therefore, early recognition and treatment of HLH are pivotal to avoid progressive tissue damage …”

“…Among them, ferritin exceeding 10 000 μg/L has a sensitivity of 90% and a specificity of 96% for the diagnosis of HLH. The level of sCD25 helps to determine the severity of the disease …”