Peripheral T-cell lymphomas: Real-world insights into clinical features and prognosis

Abstract Introduction: Peripheral T-cell lymphomas (PTCLs) are associated with poor prognosis. Subtypes include peripheral T-cell lymphoma not otherwise specified (PTCL-NOS), angioimmunoblastic T-cell lymphoma (AITL), and anaplastic large cell lymphoma (ALCL), either ALK-positive or ALK-negative. Despite evidence suggesting a higher prevalence in Latin America, information on their clinical features and outcomes in middle-income settings remain limited. Methods: A retrospective analysis was conducted on patients with PTCL at a national referral center in Mexico from 2011 to 2024. Descriptive and comparative statistics were performed. Overall survival (OS) and progression-free survival (PFS) were analyzed using Kaplan-Meier curves and log-rank test. Results: A total of 128 patients were included, with a median age of 46 years (IQR 28–64) and a male-to-female ratio of 1:1. At diagnosis, 55.5% had B symptoms, 71.1% had advanced disease (stage III–IV); 21% with bone marrow involvement, and 1.6% with CNS infiltration. ECOG was 2 in 32.8%, 3.9% had other malignancies, and 0.8% were HIV-positive. ALCL ALK-negative was diagnosed in 36.7% (47), PTCL-NOS in 35.2% (45), ALCL ALK-positive in 23.4% (30), and AITL in 4.7% (6). According to IPI, 30.2% had low risk, 33.3% low-intermediate, 21.4% high-intermediate, and 15.1% high risk. According to PIT, 27.2% had low risk, 26.2% low-intermediate, 27.2% high-intermediate, and 19.4% high risk. Regarding first-line treatment, 75% received anthracycline-based regimens, 7% brentuximab-based, and 18% did not receive systemic therapy due to severe clinical conditions. Radiotherapy was administered in 42.2%, and 13.3% underwent HSCT. The overall response rate was 54.6%, including complete response (CR) in 39.8%, and partial response (PR) in 14.8%. Disease progression occurred in 16.4%, and 28.9% were non-evaluable due to early death. Median OS was 15 months (IQR 6–81), and PFS was 9 months (IQR 4–56). Median OS and PFS by lymphoma subtype were: for AITL, 8 months (IQR 5–50) and 8 months (IQR 3–30); for PTCL-NOS, 15 months (IQR 6–90) and 8 months (IQR 4–32); for ALK-negative ALCL, 17 months (IQR 8–83) and 9 months (IQR 4–69); and for ALK-positive ALCL, 32 months (IQR 3–78) and 13 months (IQR 2–63). Advanced stage (p=0.05), ECOG 2 (p=0.021), age 60 years (p=0.042), high-intermediate to high risk IPI score (p=0.034), and PR, progression, or non-evaluable disease (p=0.0001) were associated with increased mortality. Laboratory parameters associated with poor survival included β2-microglobulin 2.5 mg/L (p=0.05; OR 2.35, 95% CI 0.96–5.73), albumin 3.5 g/dL (p=0.0001; OR 4.5, 95% CI 2–10.4), and lymphocyte count 1000/μL (p=0.047; OR 2.5, 95% CI 0.99–6.6). Relapsed or refractory (R/R) disease occurred in 35.2% and was associated with worse outcomes (p=0.014); including a 33% mortality rate, mainly due to disease progression (p=0.003). Patients whose response could not be evaluated had the poorest outcomes, with a median OS and PFS of 2 months, and a mortality rate of 43% due to failure to receive or complete induction. Clinical and laboratory predictors of relapse or progression included age 60 years (p=0.0001), bone marrow infiltration (p=0.002), advanced-stage (p=0.037), ECOG 2 (p=0.007), elevated LDH (p=0.044), β2-microglobulin 2.5 mg/L (p=0.001), albumin 3.5 g/dL (p=0.015), lymphopenia 1000/μL (p=0.09), and thrombocytopenia 100,000/μL (p=0.0001). Immunohistochemical markers associated with poor prognosis included positivity for CD3 (p=0.05), CD5 (p=0.001), and EBER (p=0.007), as well as higher Ki-67 expression 70% (p=0.017). High-intermediate or high risk according to IPI (p=0.0001) and PIT (p=0.001) scores were also associated. Treatment strategy and response influenced survival (p=0.0001). Patients treated with brentuximab-based therapy had the best OS followed by anthracycline-based regimens, as well as those with CR. Not receiving radiotherapy was associated with bad prognosis (p=0.019). Conclusion: This study provides one of the largest single-center descriptions of PTCL in Mexico and Latin America, highlighting advanced-stage disease at diagnosis, a third of R/R cases, and the limited access to targeted therapies and HSCT. Response rates and survival outcomes remain poor, particularly for PTCL-NOS and AITL. These findings underscore the urgent need for improved diagnostic and therapeutic access, and risk-adapted therapies to improve survival in this vulnerable population.