Adult malignancy-associated hemophagocytic lymphohistiocytosis: Case series.

Abstract

e19579 Background: Hemophagocytic lymphohistiocytosis (HLH) is a rare and life-threatening hyperinflammatory syndrome, with a challenging diagnosis (pediatric HLH-2004 criteria) and treatment (HLH-1994 protocol). Recently, HScore has adapted these diagnostic criteria to the adult population. Malignancy-associated HLH (M-HLH) can occur as the first manifestation of an unknown malignancy or after / during the treatment of a known cancer. This study evaluates features and outcomes of M-HLH in adult patients. Methods: Retrospective cohort study of all patients diagnosed with M-HLH in a single institution during 2013-2020. HLH-2004 and HScore criteria were used for diagnosis. Patients’ demographics, clinical and laboratory features, treatment and mortality were reviewed. Results: Eleven patients were analyzed. Ten fulfilled 5 of the HLH-2004 diagnostic criteria and one other had a HScore > 190 (80% probability of M-HLH). Median age was 68 years (IQR 62-71), and 54.5% were females. The median time between hospital admission and M-HLH diagnosis was 9 days (IQR 7-16). The most common malignancy was diffuse large B-cell lymphoma (36.4%), followed by Hodgkin lymphoma (18.2%), multiple myeloma (18.2%), myelodysplastic syndrome, T-cell and follicular lymphoma (9.1% each). Malignancy and HLH diagnosis were simultaneous in 54.5% of the cases (4 newly diagnose, 2 disease-progression); the remaining 5 patients were in remission (median time from cancer diagnosis to HLH of 9.9 months (IQR 5.1–38.3)). One patient also had an autoimmune disorder. An infectious co-trigger was identified in 81.8% of patients (virus in 45.5%, fungous in 36.4%, bacteria in 27.3%). The triad of fever, splenomegaly and cytopenia was present in 36.4% of patients. All had increased sCD25 and ferritin, with a median concentration of 7612U/mL (IQR 2631–34161) and 13269µg/L (IQR 6381–17911), respectively. The ratio between sCD25 and ferritin was 1.09 (IQR 0.13–3.05). Morphological M-HLH was documented in 8 out of the 9 biopsied cases. The HLH-1994 protocol was prescribed in 54.5% of patients (including intrathecal methotrexate in 2 patients), steroids as monotherapy were used in 18.2% and malignancy-specific chemotherapy in 36.4%. All but one patient initiated broad spectrum antibiotics at hospital admission, with an antifungal in 45.5% and an antiviral (valganciclovir) in 27.3%. At the time of analysis 63.6% of patients had died (overall, 54.5% within 3 months since M-HLH diagnosis). Conclusions: Most symptoms of M-HLH are common and unspecific, demanding a clinical suspicion and an early evaluation of ferritin, sCD25, triglycerides and fibrinogen. Co-triggers are frequent and their treatment is advisable. The disease has an unfavorable prognosis in a short period of time. This rare case series increases awareness about M-HLH (urgent need of updated diagnostic criteria and more efficient adult-adapted treatment strategies).