Hyperferritinemia and Hemophagocytic Lymphohistiocytosis. Single Institution Experience in Adult and Pediatric Patients.
Authors: Ma Alice D. , Fedoriw Yuri D. , Roehrs Philip 
Published: October 2019

Abstract 2135

Hemophagocytic lymphohistiocytosis (HLH) is a multisystem disorder characterized by immune dysregulation and hypercytokinemia. Diagnostic criteria include a genetic mutation consistent with familial HLH or the presence of 5 of 8 defined clinical criteria (fever, splenomegaly, bicytopenia, hypertriglyceridemia and/or hypofibrinogenemia, hemophagocytosis, low/absent NK cell function, hyperferritinemia, and elevated soluble CD25). In pediatrics, a ferritin value of >10,000 mχγ/L has been reported to have 90% sensitivity and 96% specificity in defining the presence of HLH (Allen, C. E., Yu, X., Kozinetz, C. A. and McClain, K. L. (2008). Pediatr. Blood Cancer).

We examined if hyperferritinemia (all patients with ferritin level >10,000 mχγ/L between 2007 and 2012) correlated with diagnosis of HLH in 94 patients (73 adult; 21 pediatric) at our institution. Chart reviews were performed to evaluate the presence or absence of HLH criteria, additional clinical features that may be indicative of HLH, and diagnosis. These data resulted in our classification of patients into four groups (Table 1): (1) “clinically defined HLH” when predetermined criteria were met; (2) “potential HLH” when clinical criteria was suggestive of HLH, but not all criteria were met; (3) “possible HLH” when rheumatologic syndromes, liver disease, or fever/DIC was present of unknown etiology; or (4) “Non-HLH” when the elevated ferritin was a result of a known etiology (Table 2). As expected, 18 (86 %) of pediatric patients with a ferritin > 10,000 mχγ/L had clinically defined or potential/possible HLH. Notably, 44 (60 %) of adult patients with a ferritin > 10,000 mg/L had clinically defined or potential/possible HLH. Such an incidence of HLH in the adult population with elevated ferritin raises caution for appropriate diagnosis of this population and clearly warrants further study. If patients with sickle cell disease, GVH, or known causes for liver failure are excluded, then HLH should be suspected in 83% of adult patients with ferritins >10,000 mcg/L.

Table 1: HLH classifications of 94 patients with ferritin > 10,000 mχγ/L Adult, n = 73 n (%) Pediatric, n = 21 n (%) Clinically defined HLH 18 (25) 12 (57) Potential HLH 9 (12) 5 (24) Possible HLH 17 (23) 1 (5) Non-HLH 29 (40) 3 (14)

Table 2: Diagnoses of non-HLH patients with ferritin > 10,000 mcg/L (some diagnoses overlap) Liver failure of clear etiology (10) APAP toxicity (4) Shock liver (4), EtOH, Other Sickle cell disease (9) 7 adult, 2 peds, all with probable iron overload Other tumors (9) CMML+VT+shock liver, prostate ca with bone mets, CMML to AML, MDS/MPD with infection, AML, T lymphoblastic lymphoma with cholestasis, allo txp for AML with iron overload, ALL+ abd wall hematoma Iron overload (11) 9 sickle cell, 1 Castlemans, 1 allo txp for AML Other Pancreatitis, GVH (3)

Table 3: Clinical suspicion for HLH Potential HLH (%) Possible HLH (%) Total Adult 9 17 Peds 5 1 HLH suspected? Adult 1 (11) 2 (12) Peds 4 (80) 1 (100) All criteria sent? Adult 1 (11) 1 (6) Peds 2 (40) 1 (100) Hematology involved? Adult 6 (67) 11 (64) Peds 5 (100) 1 (100) Did hematologist note ferritin? Adult 1 (17) 3 (27) Peds 5 (100) 0

Disclosures:

Ma: Novo Nordisk Inc.: Consultancy, Speakers Bureau.