EBV-associated T/NK–cell lymphoproliferative diseases in nonimmunocompromised hosts: prospective analysis of 108 cases

• Published in: Blood 2012-01, Vol.119 (3), p.673-686
• Main Authors: Kimura, Hiroshi, Ito, Yoshinori, Kawabe, Shinji, Gotoh, Kensei, Takahashi, Yoshiyuki, Kojima, Seiji, Naoe, Tomoki, Esaki, Shinichi, Kikuta, Atsushi, Sawada, Akihisa, Kawa, Keisei, Ohshima, Koichi, Nakamura, Shigeo
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Biological and medical sciences; Child; Child, Preschool; DNA, Viral - genetics; Epstein-Barr Virus Infections - complications; Epstein-Barr Virus Infections - pathology; Epstein-Barr Virus Infections - virology; Female; Follow-Up Studies; Hematologic and hematopoietic diseases; Herpesvirus 4, Human - genetics; Herpesvirus 4, Human - immunology; Herpesvirus 4, Human - isolation & purification; Humans; Immunocompromised Host; Infant; Infectious diseases; Killer Cells, Natural - immunology; Killer Cells, Natural - pathology; Killer Cells, Natural - virology; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymphoproliferative Disorders - etiology; Lymphoproliferative Disorders - mortality; Lymphoproliferative Disorders - pathology; Male; Medical sciences; Middle Aged; Polymerase Chain Reaction; Prognosis; Prospective Studies; Survival Rate; Viral diseases; Young Adult
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2011-10-381921

EBV-associated T/NK–cell lymphoproliferative disease (T/NK-LPD) is defined as a systemic illness characterized by clonal proliferation of EBV-infected T or NK cells. We prospectively enrolled 108 nonimmunocompromised patients with this disease (50 men and 58 women; median onset age, 8 years; age range, 1-50 years) evidenced by expansion of EBV+ T/NK cells in the peripheral blood; these were of the T-cell type in 64 cases and of the NK-cell type in 44, and were clinically categorized into 4 groups: 80 cases of chronic active EBV disease, 15 of EBV-associated hemophagocytic lymphohistiocytosis, 9 of severe mosquito bite allergy, and 4 of hydroa vacciniforme. These clinical profiles were closely linked with the EBV+ cell immunophenotypes. In a median follow-up period of 46 months, 47 patients (44%) died of severe organ complications. During the follow-up, 13 patients developed overt lymphoma or leukemia characterized by extranodal NK/T-cell lymphoma and aggressive NK-cell leukemia. Fifty-nine received hematopoietic stem cell transplantation, 66% of whom survived. Age at onset of disease (≥ 8 years) and liver dysfunction were risk factors for mortality, whereas patients who received transplantation had a better prognosis. These data depict clinical characteristics of systemic EBV+ T/NK-LPD and provide insight into the diagnostic and therapeutic approaches for distinct disease.