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 10(9)/L vs. 9.6 10(9)/L), lymphocyte count (4.9 10(9)/L vs. 2.2 10(9)/L), absolute Sézary count (3.22 10(9)/L vs. 0.99 10(9)/L), CD4 count (3.17 10(9)/L vs. 1.36 10(9)/L), and CD4:CD8 ratio (15.86 vs. 3.21). An expanded population of T-cells of a specific TCR variable beta 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.
Fraser-Andrews
E A
EA
Skin Tumor Unit, St. John's Institute of Dermatology, St. Thomas' Hospital, Lambeth Palace Road, London, SE1 7EH, United Kingdom. efraser-andrews@doctors.org.uk
Russell-Jones
R
R
Woolford
A J
AJ
Wolstencroft
R A
RA
Dean
A J
AJ
Whittaker
S J
SJ
D000328:Adult; D000368:Aged; D016516:CD4-CD8 Ratio; D004247:DNA / Q000032:analysis; D005260:Female; D015329:Gene Rearrangement, T-Lymphocyte; D019672:Genes, T-Cell Receptor; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011379:Prognosis; D016016:Proportional Hazards Models; D012751:Sezary Syndrome / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D016019:Survival Analysis
D004247:DNA