International Peripheral T-Cell Lymphoma (PTCL) Clinical and Pathologic Review Project: Poor Outcome by Prognostic Indices and Lack of Efficacy with Anthracyclines.
Authors: Vose Julie M. ,   The International PTCL Project
Published: April 2020

The clinical and pathologic features of PTCL using the new World Health Organization (WHO) classification are not well defined. Therefore, we identified 1162 patients diagnosed with de novo PTCL or natural killer (NK)/T-cell lymphoma from 1990 to 2002 at 20 sites in North America, Europe, and Asia. To be eligible, patients needed to be previously untreated, have adequate clinical information with follow up, and pathology slides with immunophenotyping available for a central review. Panels of four expert hematopathologists reviewed all the pathologic materials for each case individually and arrived at a consensus diagnosis according to the WHO classification. The clinical information was submitted and centralized in a database along with the pathology data. The pathology review identified the following case distribution: PTCL-unspecified 22.6%, angioimmunoblastic 18.3%, NK/T-cell 11.7%, diagnoses other than a T-cell lymphoma (10.9%), adult T-cell leukemia/lymphoma (10.7%), anaplastic large cell lymphoma (ALCL-ALK pos) 7.3% and ALCL-ALK neg 5.7%, enteropathy type 4.8%, unclassifiable T-cell lymphoma (2.3%), primary cutaneous ALCL (2.0%), hepatosplenic T-cell (1.5%), subcutaneous panniculitis-like (1.0%), other NK/T-cell (0.9%), blastic NK-cell (0.2%), and gamma-delta T-cell (0.1%). The agreement with the consensus diagnosis ranged from 66 – 98%. Overall clinical characteristics for the patients included a median age of 58 years (range 3 – 92 years), 62% male, 68% stage III/IV, 48% with "B" symptoms, 38% non-ambulatory, 11% with a mass &gt; 10 cm, 20% bone marrow involvement, 31% extranodal disease, 48% with a lactic dehydrogenase (LDH) &gt; normal. Using the standard International Prognostic Index (IPI), 19% had IPI 0/1, 53% IPI 2/3, and 28% IPI 4/5. For all 1162 patients, the 5-year failure-free survival (FFS) is 23% and the 5-year overall survival (OS) is 36%. A multivariate analysis of the two most common types, PTCL-unspecified and angioimmunoblastic, demonstrated the following factors to predict poor OS [poor performance status (p = 0.01), age &gt; 60 years (p = 0.02), platelets &lt; 150K (p&lt; 0.001)]. Factors associated with worse FFS included poor performance status (p &lt; 0.01) and platelets &lt; 150K (p &lt; 0.01). Unlike diffuse large B-cell lymphoma, there was no difference in overall survival comparing patients who did and did not receive an anthracycline for any subtype of PTCL. Comparison of the standard IPI, the T-cell Index (Blood103: 2474–2479, 2004), and our new International T-cell Index on this population demonstrates that in all 3 indices, the FFS and OS are very poor for all patients other than in those with 0 or 0/1 risk factors.

Comparison of Prognostic Indices PTCL + Angioimmunoblastic Risk Factors 5-yr FFS 5-yr OS Standard IPI 0/1 32% 49% 2 14% 31% 3 12% 17% 4/5 12% 21% p &lt; 0.001 p &lt; 0.001 Published T-cell Index 0 37% 53% 1 17% 33% 2 11% 18% 3/4 15% 25% p &lt; 0.001 p&lt; 0.001 Current International T-cell Index 0 21% 42% 1 19% 27% 2 10% 19% 3 5% 12% p &lt; 0.001 p &lt; 0.001

In conclusion, the prognosis of most subtypes of PTCL and NK/T-cell lymphoma is poor with standard lymphoma therapies. Novel agents and combinations are needed for improvement in the clinical outcome of these patients.