ABCL-297 Hemophagocytic Lymphohistiocytosis Singularity: A Multicenter Retrospective Study

Abstract

Hemophagocytic lymphohistiocytosis (HLH) is characterized by an excessive inflammatory response due to aberrant activation of macrophages and T lymphocytes. Cases of primary HLH (genetic mutations) are usually diagnosed in childhood, while secondary cases (due to neoplasms or infections, among others) appear predominantly in adults. Early diagnosis and treatment are essential to reduce the high mortality rate associated with this syndrome. A retrospective multicenter analysis of 55 patients diagnosed with HLH between 2004 and 2021 in five Spanish centers was performed. The main etiologies, treatment strategies employed, and the evolution of the patients are described. Median age at diagnosis was 54 years (range 0-82). All patients in whom the determination was performed presented hyperferritinemia (>10000ng/mL in 56.5%) and 89% had cytopenias. Bone marrow hemophagocytosis was observed in 87.3%. HLH was primary in 4 patients (3 of them belonged to the same family and had a homozygous mutation in the UNC13D gene) and the remaining 92.7% were secondary, with the most frequent causes being neoplasms (45.1%, mostly lymphomas) and infections (35.3%). Regarding treatment, primary HLH received the usual HLH-04 protocol (Spanish Society of HLH), which includes etoposide, corticosteroids, and cyclosporine; two patients achieved complete response (CR) and could be consolidated with allogeneic transplantation. Treatment of secondary HLH was directed at the underlying cause. Of the patients who were able to receive treatment, 42% achieved CR, with a median of 23 days to response, and only 13% of these patients relapsed. First-year overall survival was 40%. Patients with HLH secondary to neoplasia had significantly lower overall survival than those secondary to infection (30.4% vs. 66.7%; p=0.027). It should also be noted that 42% of the patients died within the first month of diagnosis and that 27% were diagnosed with necropsy, and therefore did not initiate treatment. In primary HLH the only potentially curative treatment is allogeneic transplantation. In secondary HLH a high diagnostic suspicion is essential in order to identify and treat the underlying etiology. The prognosis of the disease continues to be disappointing, so efforts should focus on early diagnosis and the search for new therapeutic strategies.