Serum soluble CD25 and ferritin in distinguishing patients with uncomplicated hematologic malignancies from patients with hematologic malignancies complicated by hemophagocytic lymphohistiocytosis.

Abstract

e20072 Background: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyper-inflammatory syndrome with distinct clinical and laboratory features. In adults, HLH is often associated with underlying malignancy, most commonly hematologic malignancies (HM). HLH occurs in 1% of adults with HM and overall survival can be low as 10-20%. Abnormal serum levels of the inflammatory markers sCD25 and ferritin are diagnostic criteria for familial HLH. However, because these reactants are often elevated in malignancy, appropriate levels for diagnosis in HM-HLH are unknown. In this study, we establish optimal sCD25 and ferritin levels for the diagnosis of HM-HLH in adults. Methods: Patients from three centers in Israel and Japan with HM-HLH and HM in whom sCD25 testing was performed were studied. The diagnosis of HLH was according to the HLH 2004 diagnostic criteria. Initial (at HLH presentation) and the maximum ferritin levels were analyzed. Sensitivity, specificity, and optimal cutoffs were calculated by receiver operating characteristic (ROC). Results: 62 patients with HM's without HLH and 40 patients with HM-HLH were included. The distribution of ages and HM subtypes was similar between groups (mostly B cell, T/NK cell, and Hodgkin's lymphoma). The median sCD25 concentration in HM was 1776 U/ml versus 8077 U/ml in HM-HLH. The median initial/ maximum ferritin levels were 190/202 ng/ml for the HM group and 2267/4515 ng/ml for the HM-HLH group. Both sCD25 and ferritin were very sensitive but nonspecific. sCD25 > 2400 U/ml had a sensitivity/specificity of 95%/65%, while initial ferritin > 500 ng/ml had a sensitivity/specificity of 95%/75%. ROC analysis demonstrated optimal confirmatory cutoff values (maximizing specificity) of > 10,056 ng/ml for sCD25 (sensitivity/specificity 47%/95%). While initial ferritin demonstrated a cutoff of > 5231 ng/ml (sensitivity/specificity 22.5%/95%, AUC = 0.88) the maximum ferritin performed better with the cutoff of > 5748 ng/ml (sensitivity/specificity 45%/95%, AUC = 0.92). Conclusions: Our data suggest that the current HLH 2004 criteria of ferritin > 500 ng/ml and sCD25 > 2400 U/ml are effective screening criteria for the complication of HLH in HM patients. sCD25 > 10,000 U/ml and initial ferritin > 5,200 ng/ml are highly specific. Patients with suspected HM- HLH should have serial ferritin testing which increases specificity of this test. Future prospective studies are needed to confirm these findings.