HLA-DR4 predicts haematological response to cyclosporine in T-large granular lymphocyte lymphoproliferative disorders.
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.
Battiwalla
Minoo
M
Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Melenhorst
Jos
J
Saunthararajah
Yogen
Y
Nakamura
Ryotaro
R
Molldrem
Jeffrey
J
Young
Neal S
NS
Barrett
A John
AJ
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
D015415:Biomarkers; D015804:HLA-DR4 Antigen; D007166:Immunosuppressive Agents; D016572:Cyclosporine