Large Granular Lymphocyte Expansion after Allogeneic Hematopoietic Stem Cell Transplant Is Associated with a Cytomegalovirus Reactivation and Shows an Indolent Outcome

• Published in: Biology of blood and marrow transplantation Vol. 18; no. 11; pp. 1765 - 1770
• Main Authors: Nann-Rütti, Sabine, Tzankov, Alexander, Cantoni, Nathan, Halter, Jörg, Heim, Dominik, Tsakiris, Dimitrios, Arber, Caroline, Buser, Andreas, Gratwohl, Alois, Tichelli, André, Rovó, Alicia
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-11-2012
• Subjects: Acute Disease; Adolescent; Adult; Aged; CD3 Complex - immunology; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - pathology; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - pathology; Child; CMV; Cross-Sectional Studies; Cytomegalovirus - physiology; Cytomegalovirus Infections - etiology; Cytomegalovirus Infections - immunology; Cytomegalovirus Infections - pathology; Cytomegalovirus Infections - virology; Female; Graft vs Host Disease - etiology; Graft vs Host Disease - immunology; Graft vs Host Disease - pathology; GVHD; Hematology, Oncology and Palliative Medicine; Hematopoietic Stem Cell Transplantation - adverse effects; Humans; Immunophenotyping; LGL; Male; Middle Aged; Risk Factors; Stem cell transplant; Transplantation, Homologous; Virus Activation; LGL; GVHD; Stem cell transplant; CMV
• ISSN: 1083-8791; 1523-6536
• DOI: 10.1016/j.bbmt.2012.07.007

Expansions of CD3+ large granular lymphocytes (LGLs) after allogeneic hematopoietic stem cell transplantation (HSCT) have been described. We sought to evaluate incidence, characteristics, and clinical significance of persistent T cell (T-)LGL after HSCT. Fourteen of 215 recipients (7%) were diagnosed with LGL expansions. Thirteen showed a CD3+/CD8+ immunophenotype, 5 of them with clonal TCR-γ rearrangement. The lymphocytes appeared at a median of 16 months (range, 3-58 months) after HSCT and lasted for a median time of 31 months (range, 2-179 months). Cytomegalovirus (CMV) reactivation ( P = .001) and acute graft-versus-host disease (aGVHD) were associated with LGL expansion ( P = .02). In the multivariate analysis, only CMV reactivation showed a significant association with T-LGL expansion (relative risk [RR]: 5.063; 95% confidence interval [CI]: 1.586-16.160; P = .006). The observed posttransplantation LGL expansions, even if monoclonal, showed a chronic, indolent course. Our data indicate that such expansions may be considered as an expression of chronic stimulation, triggered by CMV reactivation rather than a malignant transformation.