Cancer Research and Treatment

Original Articles

Hematologic malignancy

Current Treatment Patterns and the Role of Upfront Autologous Stem Cell Transplantation in Patients with Peripheral T-Cell Lymphoma: A Korean Nationwide, Multicenter Prospective Registry Study (CISL 1404): Hyungwoo Cho, Dok Hyun Yoon, Dong-Yeop Shin, Youngil Koh, Sung-Soo Yoon, Seok Jin Kim, Young Rok Do, Gyeong-Won Lee, Jae-Yong Kwak, Yong Park, Min Kyoung Kim, Hye Jin Kang, Jun Ho Yi, Kwai Han Yoo, Won Sik Lee, Byeong Bae Park, Jae Cheol Jo, Hyeon-Seok Eom, Hyo Jung Kim, Seong Hyun Jeong, Young-Woong Won, Byeong Seok Sohn, Ji-Hyun Kwon, Cheolwon Suh, Won Seog Kim; Cancer Res Treat. 2023;55(2):684-692. Published online January 2, 2023; DOI: https://doi.org/10.4143/crt.2022.1434

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Purpose
We conducted a nationwide, multicenter, prospective registry study for newly diagnosed patients with peripheral T-cell lymphoma (PTCL) to better define the clinical characteristics, treatment patterns, survival outcomes, and the role of upfront autologous stem cell transplantation (ASCT) in these patients.
Materials and Methods
Patients with PTCL receiving chemotherapy with curative intent were registered and prospectively monitored. All patients were pathologically diagnosed with PTCL.
Results
A total of 191 patients with PTCL were enrolled in this prospective registry study. PTCL, not otherwise specified (PTCL-NOS) was the most common pathologic subtype (n=80, 41.9%), followed by angioimmunoblastic T-cell lymphoma (AITL) (n=60, 31.4%). With a median follow-up duration of 3.9 years, the 3-year progression-free survival (PFS) and overall survival (OS) rates were 39.5% and 60.4%, respectively. The role of upfront ASCT was evaluated in patients who were considered transplant-eligible (n=59). ASCT was performed as an upfront consolidative treatment in 32 (54.2%) of these patients. There were no significant differences in PFS and OS between the ASCT and non-ASCT groups for all patients (n=59) and for patients with PTCL-NOS (n=26). However, in patients with AITL, the ASCT group was associated with significantly better PFS than the non-ASCT group, although there was no significant difference in OS.
Conclusion
The current study demonstrated that the survival outcomes with the current treatment options remain poor for patients with PTCL-NOS. Upfront ASCT may provide a survival benefit for patients with AITL, but not PTCL-NOS.

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Successful Treatment, with Chemotherapy and Intravenous Administration of Ascorbic Acid, of a Patient with Peripheral T-Cell Lymphoma, Not Otherwise Specified
Chiaki Tokoro, Atsushi Tashiro, Kenji Ina, Yoshiteru Tanaka, Hiroyuki Kobayakawa, Takashi Yoshida, Satoshi Kayukawa
Journal of Cancer Research Updates.2024; 13: 1. CrossRef
Role of upfront autologous transplant for peripheral T-cell lymphoma patients achieving a complete remission with first-line therapy: a systematic review and meta-analysis
L. Girard, Y. J. Koh, L. P. Koh, Y. L. Chee, H. L. Chan, J. Lee, S. de Mel, L. M. Poon, M. Samuel
Bone Marrow Transplantation.2024; 59(6): 838. CrossRef
Angioimmunoblastic T-cell lymphoma and correlated neoplasms with T-cell follicular helper phenotype: from molecular mechanisms to therapeutic advances
Luís Alberto de Pádua Covas Lage, Hebert Fabricio Culler, Cadiele Oliana Reichert, Sheila Aparecida Coelho da Siqueira, Juliana Pereira
Frontiers in Oncology.2023;[Epub] CrossRef
Advances in the pathogenesis and therapeutic strategies of angioimmunoblastic T-cell lymphoma
Qingyang Zhang, Le Yin, Qinqiao Lai, Yan Zhao, Hongling Peng
Clinical and Experimental Medicine.2023; 23(8): 4219. CrossRef

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Circulating Tumor DNA–Based Genotyping and Monitoring for Predicting Disease Relapses of Patients with Peripheral T-Cell Lymphomas: Seok Jin Kim, Yeon Jeong Kim, Sang Eun Yoon, Kyung Ju Ryu, Bon Park, Donghyun Park, Duck Cho, Hyun-Young Kim, Junhun Cho, Young Hyeh Ko, Woong-Yang Park, Won Seog Kim; Cancer Res Treat. 2023;55(1):291-303. Published online March 2, 2022; DOI: https://doi.org/10.4143/crt.2022.017

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Purpose
Plasma circulating tumor DNA (ctDNA) could reflect the genetic alterations present in tumor tissues. However, there is little information about the clinical relevance of cell-free DNA genotyping in peripheral T-cell lymphoma (PTCL).
Materials and Methods
After targeted sequencing plasma cell-free DNA of patients with various subtypes of PTCL (n=94), we analyzed the mutation profiles of plasma ctDNA samples and their predictive value of dynamic ctDNA monitoring for treatment outcomes.
Results
Plasma ctDNA mutations were detected in 53 patients (56%, 53/94), and the detection rate of somatic mutations was highest in angioimmunoblastic T-cell lymphoma (24/31, 77%) and PTCL, not otherwise specified (18/29, 62.1%). Somatic mutations were detected in 51 of 66 genes that were sequenced, including the following top 10 ranked genes: RHOA, CREBBP, KMT2D, TP53, IDH2, ALK, MEF2B, SOCS1, CARD11, and KRAS. In the longitudinal assessment of ctDNA mutation, the difference in ctDNA mutation volume after treatment showed a significant correlation with disease relapse or progression. Thus, a ≥ 1.5-log decrease in genome equivalent (GE) between baseline and the end of treatment showed a significant association with better survival outcomes than a < 1.5-log decrease in GE.
Conclusion
Our results suggest the clinical relevance of plasma ctDNA analysis in patients with PTCL. However, our findings should be validated by a subsequent study with a larger study population and using a broader gene panel.

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Clinical use of circulating tumor DNA analysis in patients with lymphoma
Bettina Bisig, Karine Lefort, Sylvain Carras, Laurence de Leval
Human Pathology.2025; 156: 105679. CrossRef
Feasibility of Circulating Tumor DNA Detection in the Cerebrospinal Fluid of Patients With Central Nervous System Involvement in Large B-Cell Lymphoma
Seok Jin Kim, Jin Ju Kim, Mi Ri Park, Bon Park, Kyung Ju Ryu, Sang Eun Yoon, Won Seog Kim, Saeam Shin, Seung-Tae Lee
Annals of Laboratory Medicine.2025; 45(1): 90. CrossRef
Circulating tumor DNA in lymphoma: technologies and applications
Lina Fu, Xuerong Zhou, Xiaoyu Zhang, Xuhua Li, Fan Zhang, Hongcang Gu, Xiaoxue Wang
Journal of Hematology & Oncology.2025;[Epub] CrossRef
Liquid biopsy in T-cell lymphoma: biomarker detection techniques and clinical application
Zongyao Huang, Yao Fu, Hong Yang, Yehan Zhou, Min Shi, Qingyun Li, Weiping Liu, Junheng Liang, Liuqing Zhu, Sheng Qin, Huangming Hong, Yang Liu
Molecular Cancer.2024;[Epub] CrossRef
Feasibility of Circulating Tumor DNA Analysis in Patients with Follicular Lymphoma
Sang Eun Yoon, Seung-Ho Shin, Dae Keun Nam, Junhun Cho, Won Seog Kim, Seok Jin Kim
Cancer Research and Treatment.2024; 56(3): 920. CrossRef
Minimal residual disease detection in lymphoma: methods, procedures and clinical significance
Sijun Zhang, Xiangyu Wang, Zhenzhen Yang, Mengjie Ding, Mingzhi Zhang, Ken H. Young, Xudong Zhang
Frontiers in Immunology.2024;[Epub] CrossRef
Clinical applications of circulating tumor DNA in hematological malignancies: From past to the future
Jun-Ying Li, Li-Ping Zuo, Jian Xu, Chun-Yan Sun
Blood Reviews.2024; 68: 101237. CrossRef
A practical approach to the modern diagnosis and classification of T- and NK-cell lymphomas
Laurence de Leval, Philippe Gaulard, Ahmet Dogan
Blood.2024; 144(18): 1855. CrossRef
In-depth circulating tumor DNA sequencing for prognostication and monitoring in natural killer/T-cell lymphomas
Jin Ju Kim, Hyun-Young Kim, Zisun Choi, So yoon Hwang, Hansol Jeong, Jong Rak Choi, Sang Eun Yoon, Won Seog Kim, Sun-Hee Kim, Hee-Jin Kim, Sang-Yong Shin, Seung-Tae Lee, Seok Jin Kim
Frontiers in Oncology.2023;[Epub] CrossRef
Circulating tumor DNA in NK/T and peripheral T cell lymphoma
Yu-Jia Huo, Wei-Li Zhao
Seminars in Hematology.2023; 60(3): 173. CrossRef
A genetic profiling guideline to support diagnosis and clinical management of lymphomas
Margarita Sánchez-Beato, Miriam Méndez, María Guirado, Lucía Pedrosa, Silvia Sequero, Natalia Yanguas-Casás, Luis de la Cruz-Merino, Laura Gálvez, Marta Llanos, Juan Fernando García, Mariano Provencio
Clinical and Translational Oncology.2023; 26(5): 1043. CrossRef

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Predictive Factors of Event-Free Survival at 24 Months in Patients with Peripheral T-Cell Lymphoma: A Retrospective Study: Yu Ri Kim, Soo-Jeong Kim, Hye Sun Lee, Soyoung Jeon, Hyunsoo Cho, Haerim Chung, Ji Eun Jang, June-Won Cheong, Yoo Hong Min, Jin Seok Kim; Cancer Res Treat. 2022;54(2):613-620. Published online August 5, 2021; DOI: https://doi.org/10.4143/crt.2021.270

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Purpose
Event-free survival at 24 months (EFS24) is known to be a surrogate marker for overall survival (OS) for patients with peripheral T-cell lymphoma (PTCL). We examined the role of EFS24 in PTCL compared to diffuse large B-cell lymphoma (DLBCL), and then assessed the clinical predictive factors of achieving EFS24.
Materials and Methods
Patients with newly diagnosed PTCL treated with anthracycline-based chemotherapy were included. Subsequent OS was defined as the time elapsed from 24 months after diagnosis until death from any cause in those who achieved EFS24.
Results
Overall, 153 patients were evaluated, and 51 patients (33.3%) achieved EFS24. Patients who achieved EFS24 showed superior OS compared to patients who did not (p < 0.001). EFS24 could stratify the subsequent OS although it did not reach to that of the general population. After matching the PTCL group to the DLBCL group based on the international prognostic index, the subsequent OS in patients who achieved EFS24 was similar between the two groups (p=0.094). Advanced stage was a significant factor to predict the failing EFS24 by multivariable analysis (p < 0.001).
Conclusion
Patients with PTCL who achieve EFS24 could have a favorable subsequent OS. Since advanced disease stage is a predictor of EFS24 failure, future efforts should focus on developing novel therapeutic strategies for PTCL patients presenting with advanced disease.

Citations

Citations to this article as recorded by

Prognostic impact of pre-treatment and post-treatment plasma Epstein-Barr virus DNA in peripheral T-cell lymphomas
Chu-Yi Chan, Tung-Liang Lin, Ming-Chung Kuo, Yu-Shin Hung, Hung Chang, Che-Wei Ou, Jin-Hou Wu, Hsuan-Jen Shih, Yi-Jiun Su, Lee-Yung Shih, Yuen-Chin Ong, Wen-Yu Chuang, Hsiao-Wen Kao
Annals of Medicine.2025;[Epub] CrossRef
Clinical significance and predictive risk factors for event-free survival at 24 months in patients with PTCL, NOS
Zheng Cao, Xiaojun Wang, Xuemin Xue, Xiaoli Feng
Annals of Hematology.2024; 103(3): 869. CrossRef
Validity of event-free survival as a surrogate endpoint in haematological malignancy: Review of the literature and health technology assessments
Sarit Assouline, Adriana Wiesinger, Clare Spooner, Jelena Jovanović, Max Schlueter
Critical Reviews in Oncology/Hematology.2022; 175: 103711. CrossRef

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Clinicopathologic Comparison of Intermediate or High Grade Peripheral T-Cell Lymphoma with Diffuse B-Cell Lymphoma: Kyung Hae Jung, In Sook Woo, Heung Moon Chang, Dae Seog Heo, Yung Jue Bang, Chul Woo Kim, Seonyang Park, Byoung Kook Kim, Noe Kyeong Kim; J Korean Cancer Assoc. 1997;29(1):136-145.

Abstract PDF: PURPOSE
Peripheral T-cell lymphoma (PTCL) derived from mature T cells forms morphologically diverse group of non-Hodgkin's lymphomas and the clinicopathologic features remain to be debated. In order to elucidate the specific characteristics of PTCL, comparison with a group of diffuse B-cell lymphomas (DBCL) was done.
MATERIALS AND METHODS
Between Dec. 1989 and Feb. 1993, clinical data of 67 cases of intermediate or high grade NHL identified as T-cell or B-cell origin by immunophenotyping was reviewed.
RESULTS
There were 30 cases of PTCL and 37 cases of DBCL. PTCL had more advanced stage and B symptoms at diagnosis. Frequent sites of extranodal involvement were bone marrow, nasal cavity/paranasal sinus, and skin in PTCL and gastrointestinal tract in DBCL. Based on NCI Working Formulation, 40% of PTCL and 14% of DBCL were high grade. Patients with DBCL had a better 3-year overall survival rate (67% vs 47%), however, there was no difference in complete remission rate and disease-free survival rate between two groups with intensive treatment. A subgroup of PTCL patients who had died earlier was found to have more advanced stage and poor performance status.
CONCLUSION
Although patients with PTCL had worse survival in advanced stage, the outcome of patients with PTCL who received intensive treatment was comparable to that of DBCL.

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