Risk Factor Analysis Of Non-Hodgkin Lymphoma-Associated Hemophagocytic Syndromes: A Multicenter Study

Hemophagocytic lymphohistiocytosis (HLH) is often associated with malignant diseases, mainly B-cell or T/NK-cell lymphoma. However, to date, few studies have examined lymphoma-associated hemophagocytic syndrome (LAHS). Our aim was to clarify the risk factors and prognostic factors of LAHS. A total of 1,181 patients with non-Hodgkin lymphoma were analyzed at 12 institutions in Hokkaido prefecture between April 2007 and December 2011 to assess the incidence, prognosis, and risk factors of LAHS. To evaluate the risk factors for developing LAHS, patient characteristics including age, gender, and histopathology were compared between patients with and without LAHS. The cumulative incidence rate of LAHS was 3.0% (35/1,181). The mortality rate of patients with LAHS was 69% (24/35), which was significantly higher than that of patients without LAHS (29%, P<0.001). The frequency of LAHS was higher in patients with T/NK-cell lymphoma than in patients with B-cell lymphoma (11.6 vs 1.8%, P<0.001). No significant differences were observed in age or gender between patients with and without LAHS. Patient characteristics including age, gender, histopathology, clinical symptoms, treatment for LAHS, EB virus serology, and laboratory data were subsequently compared between alive and dead patients to evaluate the prognostic factor of LAHS. The results obtained showed that the mortality rate was significantly higher in patients with T/NK-cell lymphoma than in patients with B-cell lymphoma (88 vs 53%, P=0.035). The frequency of liver dysfunction, including elevated total bilirubin (T.Bil) and liver enzymes [glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT)], was higher in fatal cases than in alive cases (T.Bil, median 1.35mg/dl, range 0.6-12.7mg/dl vs median 0.9mg/dl, range 0.5-6.1mg/dl, P=0.069; GOT, median 85.5IU/L, range 16-1,076IU/L vs median 40.0IU/L, range 10-651IU/L, P=0.076; GPT, median 62.5IU/L, range 11-910IU/L vs median 31.0IU/L, range 6-362IU/L, P=0.038). Moreover, the mortality rate of patients who did not respond to initial treatments including corticosteroids was higher than that of good responders (95 vs 54%, P=0.049). EB virus serology had no significant clinical impact on the prognosis of LAHS. In conclusion, patients with T/NK-cell lymphoma showed not only higher complication rates of LAHS than those of patients with B-cell lymphoma, but also higher mortality rates after developing LAHS. Further preclinical and clinical studies are required to understand the detailed pathogenesis of LAHS and improve the prognosis of patients developing LAHS.