Clinical course and prognosis of the lymphoproliferative disease of granular lymphocytes. A multicenter study

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Abstract
Lymphoproliferative disease of granular lymphocytes (LDGL) is a recently recognized, relatively rare atypical lymphocytosis characterized by the presence of over 2000 lymphocytes with cytoplasmic azurophilic granules/mm3 in the peripheral blood. The clinical course is heterogeneous, varying from spontaneous regression to progressive, malignant disease. As a consequence, clinical intervention is not standardized. In a worldwide multicenter study, the authors observed 151 patients with LDGL for a mean follow‐up time of 29 months. Forty‐three patients were asymptomatic at the time of diagnosis. In the remaining cases, clinical symptoms included fever (41 cases), infections (58), neutropenia (47), anemia (17), and thrombocytopenia (12). In 69 cases, LDGL coexisted with an associated disease. Most patients had a nonprogressive clinical course despite the presence of severe symptoms. In 19 patients, death related to LDGL occurred within 48 months. The authors investigated which features at diagnosis were significantly associated with increased mortality. In the univariate analysis, lymph node and liver enlargement, fever at presentation, skin infiltration, a low (≦ 5000/mm3) or high (> 20,000/mm3) peripheral leukocyte count, relatively low (≦ 3000) or high (> 7000/mm3) absolute peripheral granular lymphocyte (GL) count, and a low (≦ 15%) percentage of HNK‐1‐positive cells were found to be predictors of increased mortality. In the multivariate analysis, significant independent predictors were fever at diagnosis, a low (≦ 15%) percentage of HNK‐1‐positive peripheral blood mononuclear cells (PBMC) and a relatively low (≦ 3000) GL count. These results showed that about 25% of the patients with LDGL were diagnosed after a routine blood count and had no clinical symptoms. The remaining patients were symptomatic, with some experiencing a fatal clinical course. The authors' analysis of the significant prognostic features of LDGL may help in understanding the heterogeneous nature of this syndrome.