Nodal Peripheral T-Cell Lymphoma with T Follicular-Helper Phenotype: A Different Entity? Results of the Spanish Retrospective Real-T Study

Introduction: Peripheral T-cell lymphomas (PTCL) are a heterogeneous group of mature T-cell neoplasms that generally have an unfavorable prognosis. The 2016 revision of the World Health Organization (WHO) classification includes a new subtype called nodal peripheral T-cell lymphoma with T follicular-helper phenotype (PTCL-TFH), but due to its low frequency and recent definition, its clinical course and prognosis is not well characterized. The aim of this study was to define the clinical characteristics and prognosis of this new PTCL-TFH group compared to PTCL not otherwise specified (PTCL-NOS) and angioimmunoblastic T-cell lymphoma (AITL).

Methods: Retrospective observational study carried out in a large series of patients diagnosed with PTCL (n = 175) between 2008 and 2013 in 13 Spanish hospitals. The diagnosis of these patients was centrally reviewed using archived tumor samples, reclassifying patients according to the 2016 WHO criteria. The clinical characteristics and survival of patients with PTCL-NOS, AITL and PTCL-TFH were analyzed.

Results: Of the 175 patients included in the study, 55 were PTCL-NOS and 55 AITL according to the local pathological diagnosis based on WHO 2008 criteria. After centralized review, using WHO 2016 criteria, 21 patients were classified as PTCL-NOS, 55 as AITL, and 23 as PTCL-TFH. Patient characteristics are shown in Table 1. Patients diagnosed with PTCL-TFH had a lower median age and lower-risk baseline characteristics according to IPI (International Prognostic Index) and PIT (Prognostic Index for T-cell lymphoma) indices. No significant differences were found between the three diagnoses in CD30 expression or first-line treatment, which was CHOP or CHOP-like in most patients. A significantly higher percentage of patients in the PTCL-TFH group underwent autologous hematopoietic stem cell transplant (auto-HSCT) (Table 1), the vast majority in the context of first remission (7 out of 9 patients). With a median follow-up of 54.4 months (95% CI 45.69-62.98), estimated by Kaplan‑Meier using the reverse censoring method, both progression-free survival (PFS) and overall survival (OS) were significantly higher in patients with PTCL-TFH than in those with PTCL-NOS and AITL (PFS, 24.6 months vs. 4.6 and 7.8 months, respectively, p = 0.002; OS, 52.6 months vs. 10.0 and 19.3 months, respectively, p < 0.001) (Figure 1). Multivariate analysis revealed that the histological diagnosis maintained its influence on both PFS (PTCL-NOS vs. PTCL-TFH, HR 4.05; AITL vs. PTCL-TFH, HR 2.56) and OS (PTCL-NOS vs. PTCL-TFH, HR 5.68; AITL vs. PTCL-TFH, HR 2.56), regardless of the IPI and PIT indices.

Conclusions: The results of this study support the identification of the PTCL-TFH group as a specific entity, with more favorable clinical features and prognosis than those of the other subtypes. However, these findings should be confirmed in larger patient series.