Hemophagocytic Syndrome In Early Stage Extranodal Natural Killer/T-Cell Lymphoma, Nasal Type

The purpose of this study was to investigate the incidence, clinical characteristics, and survival of hemophagocytic syndrome(HPS) in patients with Stage IE and IIE extranodal nasal-type Natural Killer/T-Cell Lymphoma(NKTCL). Three hundred and ninety patients with early stage NKTCL who received treatment between January 2008 and May 2017 were systemically reviewed. Histiocytic Society hemophagocytic lymphohistiocytosis diagnostic criteria were applied for HPS. Clinical characteristics were analyzed and compared between the patients with and without HPS. The cumulative incidence of HPS in patients with early stage NKTCL was 3.1% (12/390). Seventy-five percent (9/12) of HPS began within 5 months from treatment start for primary tumor. Incidence median time was 2.3 months (0-75 months). Except one patient’s HPS onset at late relapse after 75 months, no HPS was observed after 1 year from first treatment start for primary tumor. All of HPS patients were died within 7.1 months after HPS onset, and median survival time was 1.3 months. Ferritin (FER) which were examined in 7 patients after HPS onset were elevated significantly. The median value of FER was 12783 ng/ml (2297-92855 ng/ml). Median age of patients with HPS was 37.5 years (20-71 years). It was younger than the patients without HPS with a median age of 43 years. In multivariate logistic regression model, Ann Arbor stage II (P =0.009; HR=5.913; 95% CI, 1.550 to 22.561) and serum lactate dehydrogenase (LDH) elevated (P =0.038; HR=3.539; 95% CI, 1.071 to 11.698) at diagnosis of NKTCL were independent risk factors for developing HPS in patients with early stage NKTCL. The cumulative incidence of HPS in patients with Ann Arbor stage II and LDH elevated were 7.2% (9/125) and 6.9% (7/101), respectively. There were no significant differences in other clinical characteristics that include sex, B symptoms, ECOG performance status, primary tumor invasion (PTI), CD56 status and Ki67 expression by immunohistochemistry between the patients with and without HPS. HPS was serious life-threatening disease for early stage NKTCL. The patients with young age, Ann Arbor stage II and LDH elevated should be alerted about potential risk of HPS. FER should be considered to be examined before treatment for those early stage patients.