title: HLA-DR4 predicts haematological response to cyclosporine in T-large granular lymphocyte lymphoproliferative disorders.
abstract: T-cell large granular lymphocytic lymphoproliferative disease (T-LGL) is often associated with life-threatening cytopenias. Twenty-five subjects with anaemia and/or neutropenia caused by T-LGL were treated with cyclosporin A (CSA) 5-10 mg/kg/d for at least 3 months. Eighteen patients survived between 35 and 77 months after starting treatment. Fourteen patients [56%; 95% confidence interval (CI) 35-76%] responded to CSA with sustained improvement in the neutrophil count or transfusion independence. Seven had complete normalization of blood counts, and four achieved a durable response only after the addition of erythropoietin. Sustained response required continued low-dose CSA. In a multivariate analysis, HLA-DR4 was highly predictive of CSA responsiveness (odds ratio 18; 95% CI 1.8-184). T-LGL subtype, LGL counts after therapy, lymphocytic marrow infiltration and bone marrow cellularity did not significantly affect the probability of response. We conclude that CSA is effective in inducing haematological responses in HLA-DR4-positive patients and that T-LGL is likely to have an immune pathogenesis.
authors: Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors: Minoo
authors: M
authors: Battiwalla
authors: Jos
authors: J
authors: Melenhorst
authors: Yogen
authors: Y
authors: Saunthararajah
authors: Ryotaro
authors: R
authors: Nakamura
authors: Jeffrey
authors: J
authors: Molldrem
authors: Neal S
authors: NS
authors: Young
authors: A John
authors: AJ
authors: Barrett
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000032:analysis; D016572:Cyclosporine / Q000627:therapeutic use*; D005260:Female; D015804:HLA-DR4 Antigen / Q000032:analysis*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D015458:Leukemia, T-Cell / Q000188:drug therapy* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D015804:HLA-DR4 Antigen; D007166:Immunosuppressive Agents; D016572:Cyclosporine