Predictive Value of Clonal Peripheral Blood γTCR Rearrangement in Patients with Peripheral T-Cell Lymphoma.

Peripheral T-cell lymphoma is a rare heterogeneous disease with generally poor outcome. Known risk factors include the International Prognostic Index (IPI) and b2 microglobulin. However, there is little information on molecular risk factors. In this single center analysis we have prospectively studied the prognostic value of a clonal T-cell receptor rearrangement (TCR) determined by conventional PCR for the γTCR (sensitivity 1 in 10²) from DNA from peripheral blood MNC. Thirty nine consecutive patients diagnosed between 1987 and 2006 were assessed for clonality at diagnosis.

Patient characteristics: Median age 53 years (range 28–89). M:F = 29 vs. 10. Histological diagnosis included: PTCL-NOS 7 (18%); Large cell 1 (2.5%); Large + medium-sized 5 (13%); Pleomorphic 7 (18%); Small cell 3 (8%); Small+medium mixed cell 1 (2.5%); Lennert’s type 4 (10%); Hepatosplenic 3 (8%); Intestinal 4 (10%); Kimura’s disease: 1 (2.5%);

AILD: 3 (8%). Assessment of γTCR showed monoclonality in 24 (62%) and polyclonality in 15 (38%) patients. Patients with a monoclonal TCR had higher clinical stages, higher LDH levels, higher IPI scores, and higher ß2 microglobulin levels.

Clinical stage: CS I–III (clonal 42%; polyclonal 58%) vs. CS IV (clonal 93%; polyclonal 7%). LDH above 240 U/L (clonal 78%; polyclonal 22%). IPI 0,1 (clonal 44%; polyclonal 56%), IPI 2 (clonal 75%; polyclonal 25%), IPI 3 (clonal 87%; polyclonal 13%), IPI 4,5 (clonal 60%; 40%). ß2 microglobulin above 2 mg/L (clonal 68%; polyclonal 32%). Patients with a clonal TCR tended to be older (57 vs. 49 yrs.). No major differences were found for age and sex. Induction treatment consisted of polychemotherapy (CHOP-like=34), prednisone (1), radiation (1). 3 patients received no therapy. Nine patients received subsequent involved field radiation and 6 pts. had an autologous stem cell transplant. Significant differences were observed in terms of disease outcome: The presence of a clonal γTCR (n=24) was associated with low clinical remission rates: CR 38%, PR 21%, SD 8%, PD 33%, relapse rate 38%. Remission rates in patients with polyclonal rearrangements (n=15) were: CR 66%, PR 20%, SD 7%, PD 1%, relapse rate 47%. The estimated 3-year overall survival for the monoclonal group was 26% vs. 69% for the polyclonal group (P=0.01). Importantly, patients with CS I–III and a monoclonal γTCR rearrangement (n=10) had a similarly poor survival when compared to the monoclonal group with CS IV (n=14) (18 months vs. 12 months; P=0.23). This indicates that γTCR positivity is of particular predictive value in patients with CS I–III. The data from this unique cohort suggest that γTCR-PCR is a useful prognostic tool in patients with peripheral T-cell lymphoma.

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