Clonal T-Large Granular Lymphocyte Proliferation in Solid Organ Transplant Recipients

Abstract

Large granular lymphocytic (LGL) leukemia is a rare disorder, usually caused by clonal proliferation of CD3+ CD57+ T-LGL cells. T-cell clonality is confirmed by rearrangements of the T-cell receptor (TCR) gene. Characteristic features of T-LGL leukemia include neutropenia, anemia, and constitutional symptoms such as fatigue. Many solid organ transplant recipients experience similar symptoms and have neutropenia and anemia often attributed to immunosuppressive therapy. The purpose of this study was to determine the prevalence of T-LGL proliferation in solid organ transplant recipients and demonstrate its association with leukopenia and anemia. Twenty-three cardiac and renal transplant patients were evaluated by peripheral smear examination, flow cytometry, and TCR gene rearrangement study by polymerase chain reaction. Ten of 14 (71%) cardiac transplant patients and 4 of 9 (44%) renal transplant patients, without evidence of either allograft rejection or a viral syndrome, were found to have clonal expansion of T-LGL cells. Constitutional symptoms were present in 30% of these patients. Anemia of <10 g/dL was seen in 75% of renal transplant and 10% of cardiac transplant patients. None of these patients had significant neutropenia defined as absolute neutrophil count of 1500 μ/L. Most of the patients did not require any specific therapeutic intervention. Although TCR gene rearrangement is considered a hallmark of T-LGL leukemia, we believe that this monoclonality is not a true form of posttransplant lymphoproliferative disorder. Constant antigenic stimulus from the allograft may be the underlying etiology of clonal expansion and may contribute to cytopenias and fatigue seen in transplant patients.