Occurrence of T-Lymphocytes with Aberrant Immunophenotypes Suggestive of Mature T-Cell Neoplasms In Patients with Hairy Cell Leukemia
Authors: Kern Wolfgang , Schnittger Susanne , Haferlach Claudia , Haferlach Torsten 
Published: October 2019

Abstract
Abstract 4165
Mature T-Cell Neoplasms (MTN) comprise a heterogeneous group of diseases with largely varying clinical courses ranging from indolent cases which are asymptomatic for years to aggressive cases requiring immediate therapy. The incidence of MTN is increasing with age, however, particularly due to the large group of cases with very indolent clinical course MTN are considered underdiagnosed to a significant portion. Published data indicates that T-lymphocytes with aberrant immunophenotype, i.e. double-positive cell expressing both CD4 and CD8, are present in healthy subjects, however, their frequency in general amounts to clearly less than one percent of total leukocytes. With increasing age, these T-lymphocytes with aberrant immunophenotype are detected in more subjects and at higher frequencies suggesting a higher incidence of mature T-cell neoplasms or at least of pre-malignant conditions in these cases. The diagnosis of hairy cell leukemia has not yet been linked to a higher frequency of these T-lymphocytes with aberrant immunophenotype or of MTN. Following the identification of various cases with both a diagnosis of hairy cell leukemia and the presence of T-lymphocytes with aberrant immunophenotype in our laboratory we hypothesized that both of these conditions co-occur at a higher rate than would be expected by chance. We therefore retrospectively evaluated multiparameter immunophenotyping results of 338 patients diagnosed with hairy cell leukemia (newly diagnosed or during follow-up) between August 2005 and July 2010 for the presence of an increased percentage (more than 1%) of T-lymphocytes with an aberrant immunophenotype. We identified 31 such patients, i.e. 9.2% of all patients with hairy cell leukemia. 17 were identified at initial diagnosis and 14 during follow-up after therapy for hairy cell leukemia. The patients` ages ranged from 43.4 to 89.3 years (median, 62.1 years), 21 were male. The aberrant immunophenotype comprised the coexpression of CD3, CD4, and CD8 in all cases and in addition of CD56 in 25/31 (80.6%) cases. The median values and ranges for blood cell counts amounted to: WBC, 2.6 ×10e9/l, 1.0–24.6 ×10e9/l; hemoglobin, 12.7 g/dl, 7.3–16.5 g/dl; thrombocytes, 116 ×10e9/l, 24–258 ×10e9/l. The percentage of T-lymphocytes with an aberrant immunophenotype (compared to all leukocytes) ranged from 1% to 22% (median, 4%); the respective concentrations ranged from 0.013 ×10e9/l to 0.984 ×10e9/l (median, 0.122 ×10e9/l). The concentrations of T-lymphocytes with an aberrant immunophenotype tended to be higher in cases at follow-up as compared to those at initial diagnosis, although this difference was not significant (mean±SD, 0.266±0.275 ×10e9/l vs. 0.144±0.119 ×10e9/l). In four of the 31 patients with T-lymphocytes with an aberrant immunophenotype molecular genetic analysis of T-cell receptor (TCR) rearrangement was performed. In 3/4 patients both TCR beta and gamma were found rearranged and in one of these also TCR delta was rearranged, however, in 1/4 patient no TCR rearrangement was present. This data indicates that T-lymphocytes with aberrant immunophenotypes are present in patients with hairy cell leukemia much more often and at higher concentrations than in the general population. This data therefore suggests that the incidence of mature T-cell neoplasms may be higher in hairy cell leukemia patients. Clinical symptoms and findings like cytopenia and splenomegaly therefore may not be attributable to hairy cell leukemia alone which may have significant therapeutic implications. It is suggested to monitor for T-lymphocytes with aberrant immunophenotypes in patients with hairy cell leukemia and to perform analysis for TCR rearrangements in positive cases.

Disclosures:
Kern: MLL Munich Leukemia Laboratory: Employment, Equity Ownership. Schnittger:MLL Munich Leukemia Laboratory: Employment, Equity Ownership. Haferlach:MLL Munich Leukemia Laboratory: Employment, Equity Ownership. Haferlach:MLL Munich Leukemia Laboratory: Employment, Equity Ownership.