Isolated anemia in patients with large granular lymphocytic leukemia (LGLL)

Youssef Salama,Jennifer L Oliveira,Mithun V Shah,Min Shi,William G Morice,Ronald S Go,Sameer A Parikh,Fang Zhao,Ji Yuan,Dragan Jevremovic,Paul J Hampel,Aref Al-Kali,Wei Ding

doi:10.1038/s41408-022-00632-6

Abstract

Patients with large granular lymphocytic leukemia (LGLL) frequently present with neutropenia. When present, anemia is usually accompanied by neutropenia and/or thrombocytopenia and isolated anemia is uncommon. We evaluated a cohort of 244 LGLL patients spanning 15 years and herein report the clinicopathologic features of 34 (14%) with isolated anemia. The patients with isolated anemia showed a significantly male predominance (p = 0.001), a lower level of hemoglobulin (p < 0.0001) and higher MCV (p = 0.017) and were less likely to have rheumatoid arthritis (p = 0.023) compared to the remaining 210 patients. Of the 34 LGLL patients with isolated anemia, 13 (38%) presented with pure red cell aplasia (PRCA), markedly decreased reticulocyte count and erythroid precursors, and more transfusion-dependence when compared to non-PRCA patients. There was no other significant clinicopathologic difference between PRCA and non-PRCA patients. 32 patients were followed for a median duration of 51 months (6–199). 24 patients were treated (11/11 PRCA and 13/21 non-PRCA patients, p < 0.02). The overall response rate to first-line therapy was 83% [8/11 (72.7%) for PRCA, 12/13 (92.3%) for non-PRCA], including 14 showing complete response and 6 showing partial response with a median response duration of 48 months (12–129). Half of non-PRCA patients who were observed experienced progressive anemia. During follow-up, no patients developed neutropenia; however, 5/27 (18.5%) patients developed thrombocytopenia. No significant difference in overall survival was noted between PRCA and non-PRCA patients. In summary, this study demonstrates the unique features of LGLL with isolated anemia and underscores the importance of recognizing LGLL as a potential cause of isolated anemia, which may benefit from disease-specific treatment. LGLL patients with PRCA were more likely to require treatment but demonstrated similar clinicopathologic features, therapeutic responses, and overall survival compared to isolated anemia without PRCA, suggesting PRCA and non-PRCA of T-LGLL belong to a common disease spectrum.

Highlights

Large granular lymphocytes (LGL) are a morphologically distinct lymphoid subpopulation in the peripheral blood characterized by abundant azurophilic cytoplasmic granules
There was no significant difference between Large granular lymphocytic leukemia (LGLL) patients with and without isolated anemia for age, other malignancies, history of bone marrow or solid organ transplantation, B symptoms, splenomegaly, lymphadenopathy, absolute lymphocyte count, or absolute LGLL count
There was no significant difference between LGLL patients with and without pure red cell aplasia (PRCA) for gender, age, associated diseases, B symptoms, splenomegaly, lymphadenopathy, Hb, absolute neutrophil count (ANC), ALC, and platelet count (Table 1)

Summary

Introduction

Large granular lymphocytes (LGL) are a morphologically distinct lymphoid subpopulation in the peripheral blood characterized by abundant azurophilic cytoplasmic granules. Large granular lymphocytic leukemia (LGLL) is a clonal hematopoietic disorder caused by an abnormal expansion of LGLs in the peripheral blood, bone marrow, and spleen [1]. The pathophysiologic mechanism of LGLL is not wellunderstood, immunological stimuli, possibly from viruses or tumor antigens, have been implicated [2,3,4]. This theory has been supported by the high rate of association between LGLL and various hematologic malignancies, namely B-cell lymphoma, multiple myeloma, myeloid neoplasms, and autoimmune diseases such as rheumatoid arthritis [5,6,7,8,9,10]. NK-cell clonality can be determined by the restriction of killer-cell immunoglobulin-like receptor (KIR) [14]

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