Editor's Note: During the 2025 European Hematology Association (EHA) Annual Meeting, a session on the interpretation of the new Peripheral T-Cell Lymphoma (PTCL) guidelines drew significant attention. At this session, the European Society for Medical Oncology (ESMO) and EHA jointly released the latest clinical practice guidelines for PTCL, marking the first in-depth collaboration between the two authoritative academic organizations in this field. Leading experts, including Professor Massimo Federico from the University of Modena, Italy, and Professor Francesco D'Amore from Aarhus University Hospital, Denmark, systematically reviewed the history of PTCL diagnosis and treatment and provided a comprehensive interpretation of the core content of the new guidelines, offering the latest and most authoritative practical guidance for clinical physicians in the global hematologic oncology field.Development and Core Framework of the New Guidelines: A Decade of Refinement
At the beginning of the meeting, Professor Massimo Federico reviewed the developmental history of PTCL guidelines. He noted that significant progress has been made in the field since the first European PTCL guidelines were published in 2013. At that time, CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) or CHOP-like regimens were the standard first-line treatment for most PTCL subtypes, with Autologous Stem Cell Transplant (ASCT) being a consolidation option for high-risk patients. The 2015 ESMO guidelines first emphasized the importance of enrolling patients in clinical trials and proposed more detailed treatment recommendations for different subtypes.
Nearly a decade later, the release of the new guidelines marks the dawn of a new era. Professor Francesco D’Amore presented the grand architecture of the new guidelines using a clear matrix diagram. The guidelines horizontally cover the entire management course from first-line treatment to the relapsed/refractory (R/R) stage, while vertically providing detailed classifications for various subtypes, including nodal, extranodal, and, for the first time, leukemic PTCL. Professor D’Amore particularly emphasized, “At every decision point in the new guidelines, we have marked ‘Recommend patient enrollment in clinical trials’ with a red arrow. This is not just a slogan, but a reflection of the fact that PTCL is a group of rare and highly heterogeneous diseases. Much of our knowledge is still limited to a few common subtypes, and we urgently need to accumulate more evidence-based medical data through clinical research.”
Diagnosis, Staging, and Risk Assessment: PET-CT and Bone Marrow Biopsy Remain Cornerstones
An accurate diagnosis is the cornerstone of subsequent treatment. The new guidelines clearly state that PET-CT is the preferred imaging assessment tool for all PTCL patients. Unlike Hodgkin lymphoma or diffuse large B-cell lymphoma, bone marrow involvement is more common in PTCL; therefore, a bone marrow biopsy is listed as a mandatory examination at initial diagnosis. Professor D’Amore reminded that upon disease relapse, a repeat biopsy is crucial to confirm pathological changes. For the most common nodal PTCLs, the International Prognostic Index (IPI) scoring system remains the primary tool for assessing prognosis, with its validity confirmed in multiple studies.
In terms of response assessment, the guidelines recommend a mid-treatment PET-CT evaluation. Although adjusting therapy based on interim PET results has not significantly changed patient outcomes, data show that the response status on interim PET and the Metabolic Tumor Volume (MTV) are strong independent predictors of survival. After treatment completion, baseline imaging and bone marrow biopsy (if positive at baseline) should be repeated. For patients in sustained complete remission (CR), routine PET-CT or CT monitoring is not recommended, and follow-up can cease after 3 years. However, patients who have undergone ASCT are advised to have a 5-year follow-up to monitor for the potential risk of myelodysplastic syndrome.
First-Line Treatment Strategies: Evolution from Classic Chemotherapy to Targeted Combinations
For PTCL-Not Otherwise Specified (PTCL-NOS) and lymphomas of T-follicular helper (TFH) cell origin, the new guidelines provide detailed recommendations for patients with different stages and risk levels. For early-stage patients, combined chemo-radiotherapy is superior to a single modality. For high-risk patients with an IPI score greater than 2, the guidelines recommend more aggressive treatment strategies.
The addition of etoposide to the CHOP regimen (CHOEP) has been a focal point of discussion. Early data from the German High-Grade Non-Hodgkin Lymphoma Study Group showed that in patients ≤60 years of age with normal lactate dehydrogenase (LDH) levels, the CHOEP regimen provided an event-free survival (EFS) benefit, especially in the ALK-positive anaplastic large cell lymphoma (ALK+ ALCL) subgroup. This conclusion has been repeatedly validated in subsequent retrospective studies, establishing its role in specific populations.
The advent of targeted drugs has completely changed the treatment landscape. The ECHELON-2 study confirmed that in patients with CD30-positive PTCL, the brentuximab vedotin plus CHP regimen (BV-CHP) significantly improved patient survival compared to CHOP. Furthermore, a French team has achieved positive signals in research on the hypomethylating agent 5-azacitidine. The ORACLE study demonstrated its clear clinical activity in improving progression-free survival (PFS), and it is expected to be combined with chemotherapy in the future as a new option for first-line treatment.
The Role and Controversies of Transplantation: Weighing Autologous vs. Allogeneic Transplants
As a consolidation therapy for PTCL, the specific timing and modality of stem cell transplantation have always been a core topic of academic discussion. Professor D’Amore provided a detailed interpretation of a major head-to-head study conducted jointly by German and French groups comparing ASCT with Allogeneic Stem Cell Transplant (Allo-SCT). The final analysis showed no significant difference in 3-year EFS and overall survival (OS) between the two transplant methods. However, their failure patterns were distinctly different: the ASCT group had a treatment-related mortality (TRM) of 0 but a lymphoma relapse rate of 36%, whereas the allo-SCT group had a relapse rate of 0 but a TRM as high as 31%. Professor D’Amore concluded, “This result perfectly explains why in the new guidelines, we primarily recommend ASCT for first-line consolidation, while reserving allo-SCT for relapsed/refractory patients.”
However, whether all high-risk patients require ASCT consolidation after first-line therapy remains an open question. The French Lymphoma Study Academic Group (LYSA) has initiated the TRANSCRIPT clinical trial to answer this key question, and its results are highly anticipated.
Clinical Case Sharing: Application and Challenges of the Guidelines in the Real World
To bring the guidelines closer to clinical practice, Dr. Jana Stepanina from Riga Stradins University, Latvia, shared the complete diagnosis and treatment journey of a patient with angioimmunoblastic T-cell lymphoma (AITL). The patient presented with stage IV disease, an IPI score of 3, and concomitant autoimmune hemolytic anemia. After 6 cycles of the CHOEP regimen combined with intrathecal chemotherapy, the patient achieved a complete remission and successfully underwent ASCT for consolidation.
Unfortunately, the patient relapsed less than 6 months post-transplant. After receiving multiple second-line regimens (including DHAP and gemcitabine-based protocols), the patient again reached complete remission and successfully received a matched sibling allogeneic stem cell transplant. Dr. Stepanina stated with satisfaction, “Today, nearly 7 years after the allogeneic transplant, the patient not only remains disease-free but also enjoys a high quality of life, without any chronic graft-versus-host disease (GVHD) or other long-term complications.” This successful case vividly illustrates the treatment pathway recommended by the new guidelines: for young, eligible patients with relapsed/refractory disease, allogeneic stem cell transplantation is the only potentially curative option.
Outlook and Conclusion: A Future of Collaboration, Updates, and Precision
At the end of the meeting, Professor Martin Dreiling, Chair of the EHA Guidelines Committee, added that the field of T-cell lymphoma is advancing rapidly. To ensure the guidelines remain current, EHA has established a mechanism for regular updates, with revised content to be published annually on its official website. This first major collaboration between ESMO and EHA has set a new milestone for the PTCL field. The new guidelines not only systematically integrate the evidence-based medicine of the past decade but also provide a clear roadmap for clinical practice through detailed subtype classification, risk stratification, and individualized treatment pathway recommendations. From classic chemotherapy to targeted combinations, from autologous to allogeneic transplantation, and the exploration of emerging drugs, the creation of these guidelines will vigorously promote the standardization and precision of peripheral T-cell lymphoma diagnosis and treatment worldwide, bringing the hope of a cure to more patients.
