Professor.Francine Foss

The 2008 World Health Organization’s classification of mature T/NK-cell neoplasms distinguishes about two dozen peripheral and cutaneous T-cell lymphomas.A survey of 1,314 PTCL and NK/TCL cases from 22 sites around the world evaluated the histopathology of previously untreated patients consecutively diagnosed between 1990 and 2002. Peripheral T-Cell Lymphoma–Not Otherwise Specified (PTCL-NOS) is the most common subtype of T-cell lymphoma in the United States. Two other common subtypes include ALK+/-anaplastic large cell lymphoma (ALCL) and angioimmunoblastic lymphoma.The median overall survival (OS) for most subtypes of PTCL is 1–3 years; the 5-year OS is approximately 26%. ALK+ ALCL is an exception, with a 5-year survival of 65–90%. Most cases of PTCL-NOS consist of numerous medium-sized and/or large cells with irregular, pleomorphic, hyperchromatic, or vesicular nuclei, prominent nucleoli, and many mitotic figures. Most patients present with peripheral lymph node involvement, but any site may be affected. Extranodal presentations may occur, with the skin and gastrointestinal tract representing the most commonly affected sites. Under these circumstances, the diagnosis of PTCL-NOS should be made only when other specific entities have been excluded. Other less frequently involved sites include the lung, salivary gland, and central nervous system.

In the US, the National Comprehensive Cancer Network (NCCN) recommends chemotherapy as the first line treatment for most aggressive T-cell lymphomas, with CHOP or CHOP/Etoposide being the most commonly used regimens. Further, it is recommended that all patients except low-risk (aaIPI) should be consolidated with high-dose therapy and stem cell rescue (autologous) if the patient is a candidate for transplant.In patients with NK/T-cell lymphoma that is localized etoposide, ifosfamide, cisplatin, and dexamethasone (VIPD), dexamethasone, methotrexate, ifosfamide, L-asparaginase, and etoposide (SMILE), or gemcitabine/oxaliplatin, asparaginase and radiation therapy (XRT) may be effective. In disease that is advanced, SMILE is appropriate therapy. In patients with enteropathy-associated T-cell lymphoma (EATL) the Newcastle regimen (CHOP-ifosfamide, etoposide, epirubicin/methotrexate [IVE-MTX]) followed by ASCT is the best option.

Some of the recent agents that have demonstrated clear activity in T-cell lymphoma include brentuximabvedotin; pralatrexate; and the HDAC inhibitors, romidepsin and belinostat. Among the new and emerging therapies for TCL are mogamulizumab, an anti-CCR4 monoclonal antibody with enhanced ADCC, and the aurora kinase family of oncogenic serine-threonine kinases that regulate mitotic signaling. Ongoing phase III clinical trials in PTCL are evaluating alemtuzumab and CHOP14 plus G-CSF; alisertib versus pralatrexate or gemcitabine or romidepsin;brentuximabvedotin plus CHP versus CHOP; CHOP followed by pralatrexate versus observation;romidepsin plus CHOP versus CHOP; and belinostat plus CHOP versus CHOP. Further advances in understanding the biology of aggressive T cell lymphomas are needed to improve outcomes. To that end, two major T-cell lymphoma registries, the T-Cell Project and COMPLETE Registry, are currently recruiting patients and are actively working to coordinate worldwide data collection in these diseases.