Diagnostic and prognostic importance of T‐cell receptor gene analysis in patients with Sézary syndrome

BACKGROUND Sézary syndrome (SS) is characterized by erythroderma, peripheral lymphadenopathy, and circulating Sézary cells and is clinically heterogeneous. METHODS T‐cell receptor (TCR) gene analysis was performed using DNA extracted from peripheral blood mononuclear cells from 74 patients, and the results were correlated with a variety of other diagnostic parameters and patient outcomes. RESULTS Two groups were identified: 66 patients with clonal TCR gene rearrangement (clonal patients) detected with Southern blot analysis and/or polymerase chain reaction/single‐strand conformational polymorphism analysis and 8 patients with no clonal rearrangement detected (nonclonal patients) using either technique. Clonal patients were compared with nonclonal patients. The following median blood parameters were significantly greater in the clonal group: total white cell count (13.7 109/L vs. 9.6 109/L), lymphocyte count (4.9 109/L vs. 2.2 109/L), absolute Sézary count (3.22 109/L vs. 0.99 109/L), CD4 count (3.17 109/L vs. 1.36 109/L), and CD4:CD8 ratio (15.86 vs. 3.21). An expanded population of T‐cells of a specific TCR variable β subset was detected in 7 of 36 clonal patients and in 1 of 4 nonclonal patients. Cytogenetic analysis of peripheral blood from 1 nonclonal patient and 6 clonal patients was normal. The median survival from the time of diagnosis was 45 months in the clonal group, and 40 of 49 deaths were cutaneous T‐cell lymphoma (CTCL)‐related, whereas 3 deaths in the nonclonal group were unrelated to CTCL (P < 0.01; log‐rank test). Multivariate proportional hazards analysis showed that the absolute Sézary count and lymph node status were independent prognostic variables (P = 0.016 and P = 0.036, respectively). CONCLUSIONS TCR gene analysis defines a distinct clinicopathologic group of patients with SS. Clonal patients have a poor prognosis and are likely to die from leukemia/lymphoma, whereas nonclonal patients may have a reactive, inflammatory T‐cell disorder. The authors suggest that the definitive diagnostic criteria for patients with SS should include the presence of a clonal TCR gene rearrangement. Cancer 2001;92:1745–52. © 2001 American Cancer Society. This study of 74 patients with Sézary syndrome, a rare T‐cell leukemia/lymphoma, indicates that T‐cell receptor gene analysis defines two distinct clinicopathologic groups. Patients with clonal rearrangement have a poor prognosis and are likely to die from leukemia/lymphoma, whereas patients without clo