T-Cell Large Granular Lymphocytic Leukemia as a Cause for Severe Neutropenia

Abstract

Large granular lymphocytic (LGL) leukemia is a rare, indolent disease that can cause destruction of neutrophils. We discuss the case of a previously healthy 63-year-old male who presented with severe, recurrent febrile neutropenia, in whom three bone marrow biopsies over 13 months failed to produce a diagnosis. He presented to our facility with persistent fevers and an absolute neutrophil count of 20 cells/mm 3 (reference range 1,700-7,000 cells/mm 3). A fourth bone marrow biopsy did not show clonal proliferation, but T-cell LGL leukemia was diagnosed based on the identification of T-cell rearrangements. We propose that LGL leukemia could be an underdiagnosed cause of severe neutropenia in patients with no overt malignancy or immunosuppressive therapy and that population-based database studies of patients with unexplained neutropenia may reveal more cases of this rare disease class.

Febrile Neutropenia as the First Manifestation of T-Cell Large Granular Lymphocytic Leukemia

“…It should be noted that in medical literature some case reports of patients with neutropenia and recurrent infections ultimately diagnosed with T-LGL leukemia can be found [9,10]. In contrast with the patient in our case, those patients had a larger number of infections and were younger.…”

The Value of Flow Cytometry Clonality in Large Granular Lymphocyte Leukemia

“…From selected articles ( n = 20), data were collected into a standardized form including publication year, source, number of total patients and divided by sex, number of subjects with autoimmune disorders, hematological malignancies, or cancers, and Vβ usage by flow cytometry ( Table 2 ) [ 41 , 42 , 46 , 75 , 76 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 , 100 , 101 , 102 , 103 , 104 , 105 , 106 , 107 ]. A total of 533 T-LGL leukemia patients were evaluable for Vβ usage analysis, and sex was available in 524 subjects: 308 of them were males (58.8%) and 216 females (41.2%) with a male:female ratio of 1.4, as already described in smaller cohorts [ 1 ].…”

“…Studies were included when: (1) the year of publication was between 2011 and 2021; (2) the studies were conducted on humans and reported clinical data and Vβ usage by flow cytometry; and (3) the studies were on T-LGL leukemia (Figure 2). From selected articles (n = 20), data were collected into a standardized form including publication year, source, number of total patients and divided by sex, number of subjects with autoimmune disorders, hematological malignancies, or cancers, and Vβ usage by flow cytometry (Table 2) [41,42,46,75,76,[88][89][90][91][92][93][94][95][96][97][98][99][100][101][102][103][104][105][106][107]. A total of 533 T-LGL leukemia patients were evaluable for Vβ usage analysis, and sex was available in 524 subjects: 308 of them were males (58.8%) and 216 females (41.2%) with a male:female ratio of 1.4, as already described in smaller cohorts [1].…”