Clinical Characteristics of Hemophagocytic Lymphohistiocytosis Associated with Non-Hodgkin B-Cell Lymphoma: A Multicenter Retrospective Study.

BACKGROUND

Hemophagocytic lymphohistiocytosis (HLH) associated with B-cell lymphoma is a highly aggressive disease with unclear clinical features and has no standard treatment.

PATIENTS AND

METHODS

We analyzed the clinical characteristics of 31 patients from two individual centers.

RESULTS

The median overall survival was only 1.5 months. Both univariate and multivariate analyses, based on lymphoma or HLH-related characteristics, revealed that patients with high Epstein-Barr virus (EBV) DNA load and ≥ 2 extranodal lesions, or hypofibrinogenemia, respectively, showed significantly poorer overall survival. Interestingly, some patients with high EBV DNA load had EBV-positive natural killer (NK) and/or T cells, which may be related to the coexistence of immunodeficiency and/or chronic active EBV infection. Molecular genetics examination confirmed that 47.4% (9/19) of patients had complex karyotypes, 37.5% (3/8) of patients had TP53 deletions, and 21.34% (3/14) of patients had TP53 mutation or alteration of malignancy-related pathways, including BCR/NF-κB, JAK-STAT, and epigenetic regulatory pathways, which may provide clues to choose targets for therapy. Treatment regimens containing etoposide, anti-CD20 monoclonal antibodies, or anthracyclines improved patient prognosis (P = .0183, .025, and .0436, respectively). Patients with infections had significantly shorter survival than those without infections (P = .00019).

CONCLUSION

The patients' performance status, number of extranodal lesions, high EBV DNA load, and hypofibrinogenemia are poor prognostic factors for HLH associated with B-cell lymphoma. Molecular genetic high-risk factors are of particular importance because these factors can provide information for prognosis prediction, treatment decisions, and disease surveillance.