Pure Red Cell Aplasia Associated to Clonal CD8+ T-Cell Large Granular Lymphocytosis: Dependence on Cyclosporin A Therapy

Abstract

This case report details a single patient with pure red cell aplasia (PRCA) associated with clonal CD3+, TCRαβ+, TCR-Vβ8+, CD8+, CD57+ large granular lymphocytosis whose anaemia did not respond to conventional immunosuppressive therapy but did respond to cyclosporin A (CsA). The patient has become dependent on CsA for 7 years in order to control anaemia due to associated PRCA.

Cd8+/vβ5.1+ large granular lymphocyte leukemia associated with autoimmune cytopenias, rheumatoid arthritis and vascular mammary skin lesions: successful response to 2‐deoxycoformycin.

“…11,12 Similar responses were previously reported with cyclosphosphamide 8,9 whereas treatment with cyclosporin A may result in a clinical and hematological responses but with persistence of the abnormal LGL clone that circulates in the blood, supporting the proposal that cyclosporin A acts only at the functional level by inhibiting T-cell activation. 6,7 Our case also illustrates that combined staining with relevant T-cell associated and anti-TCR-Vb MAb is a very sensitive method for assessing the therapeutic effect and evaluating the residual disease at levels that were undetectable by molecular analysis of TCR-beta chain gene using conventional Southern blotting. The value of Southern blot for determining T-cell clonality is considerably limited when the clonal T-cell population represent a minor proportion of the total nucleated cells (e.g.…”

“…[1][2][3] Several agents, including corticosteroids, hematopoietic growth factors, high dose intravenous immunoglobulins, low dose methotrexate, cyclosporin A and cyclophosphamide have been used with variable success in the treatment of LGL-leukemia and associated conditions. [4][5][6][7][8][9] Recently, purine analogues such as fludarabine, 2-chlorodeoxyadenosine and 2-deoxycoformycin (2-DCF), have also been proved to have potent activity in the treatment of chronic T-cell leukemias, including a few cases of LGL-leukemia. [10][11][12] We describe a patient with a CD3 + /TCRab + /CD8 +bright /Vb5.1 + LGL leukemia, who presented with arthritis, mild lymphocytosis, autoimmune cytopenias (neutropenia and thrombocytopenia), recurrent infections and vascular mammary skin lesions that were successfully treated with 2-DCF.…”

T-Cell Large Granular Lymphocyte Leukemia and Related Disorders

“…Several studies report the association between LGL leukemia and pure red cell aplasia (PRCA) [43][44][45][46]. In the largest study, by Go et al [45] from the Mayo Clinic, among 203 patients with LGL leukemia, 15 (7%) presented with PRCA.…”

Phosphatidylinositol-3-phosphate kinase pathway activation protects leukemic large granular lymphocytes from undergoing homeostatic apoptosis

“…45,46 In contrast, use of immunosuppressive regimens such as low-dose methotrexate, oral cytoxan, and cyclosporine have shown greater utility. [47][48][49][50] Our results demonstrating that signal transduction pathways initiated by PI3K are active and critically important for cell survival in T-LGL provide a novel set of targets that could greatly complement current treatment strategies.A key issue regarding T-LGL pathogenesis is the question of what mechanisms are supporting the ability of the pathologic CTLs to avert normal homeostatic apoptosis. Based on previous reports of constitutive cytokine production by T-LGL, we proposed the mechanism attenuating homeostatic apoptosis might involve signaling through a cytokine receptor and activity of an antiapoptotic signal transduction pathway.…”