Cancer Research and Treatment

Review Article

Advances in T-Cell–Directed Immunotherapy for Adult Mature B-Cell Lymphoma: A Comprehensive Review of CAR T-Cell and Bispecific Antibody Therapies: Jinchul Kim, Seok Jin Kim; Received April 23, 2025 Accepted June 25, 2025 Published online June 26, 2025; DOI: https://doi.org/10.4143/crt.2025.440 [Accepted]

Abstract PDF: B-cell lymphomas are a heterogeneous group of malignancies with a high relapse rate after conventional therapies. T-cell–mediated immunotherapies, notably chimeric antigen receptor (CAR) T-cell therapies and T-cell–engaging bispecific antibodies (BsAbs), have transformed treatment paradigms by harnessing the immune system to target malignant cells. This review analyzes the efficacy and safety profiles of several CD19-targeted CAR T-cell therapies and emerging CD20xCD3 BsAbs across various B-cell lymphoma subtypes. While these therapies have demonstrated high response rates and potential for durable remissions, challenges such as cytokine release syndrome, neurotoxicity, and infections remain significant. Understanding these mechanisms and managing adverse effects are crucial for optimizing clinical outcomes and guiding future research in personalized treatment strategies.

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Original Articles

Cost-Effectiveness Analysis of Daratumumab Monotherapy and Subsequent Therapies in Heavily Treated Relapsed/Refractory Multiple Myeloma: A Feasible Methodology using a Korean Nationwide Population Cohort: Sung-Soo Park, Suein Choi, Seungpil Jung, Seunghoon Han, Chaehyeon Lee, Jinseon Han, Soyoung Kim, Kihyun Kim, Chang-Ki Min; Received January 10, 2025 Accepted April 13, 2025 Published online April 15, 2025; DOI: https://doi.org/10.4143/crt.2025.046 [Accepted]

Abstract PDF: Purpose
High-cost novel therapies for multiple myeloma (MM) require evaluation of efficacy and cost-effectiveness.
Materials and Methods
This study developed a methodology to assess cost-effectiveness using nationwide data from 11,450 newly diagnosed MM patients. A novel algorithm was applied to identify lines of therapy (LoT).
Results
The number of newly diagnosed MM patients increased significantly, from 873 in 2010 to 1,464 in 2019 (p<0.001). Advancing LoT was associated with shorter time to next treatment (TTNT) and overall survival (OS) (p<0.001), while all-cause medical costs increased with each LoT (p<0.001). bortezomib-melphalan-prednisolone was the most common frontline regimen for transplant-ineligible patients (29.2%), while bortezomib-thalidomide-dexamethasone was most used for transplant-eligible patients (11.3%). Daratumumab monotherapy demonstrated superior second TTNT (7.8 vs. 5.2 months) and OS (8.5 vs. 5.3 months) compared to standard care in heavily treated MM patients, with statistical significance maintained after cost adjustment. For subsequent therapies following daratumumab, a methodology was developed to estimate required medical costs using the incremental cost-effectiveness ratio (ICER): Expected cost, $ = ICER × (Expected life expectancy – 0.567) + 35,601.
Conclusion
This study provides a novel cost-effectiveness framework linking treatment efficacy and real-world costs, supporting predictions of societal costs for future MM therapies.

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Hematologic malignancy

Clinical Impact of Microbiome Characteristics in Treatment-Naïve Extranodal NK/T-Cell Lymphoma Patients: Sang Eun Yoon, Woorim Kang, Junhun Cho, Mauricio Chalita, Je Hee Lee, Dong-Wook Hyun, Hyun Kim, Seok Jin Kim, Won Seog Kim; Cancer Res Treat. 2025;57(2):597-611. Published online August 16, 2024; DOI: https://doi.org/10.4143/crt.2024.675

Abstract PDF Supplementary Material PubReader ePub: Purpose
Extranodal natural killer/T-cell lymphoma (ENKTL) predominantly manifests in East Asia and Latin America. Despite shared intrinsic factors, such as ethnic and genetic backgrounds, the progression of ENKTL can be influenced by extrinsic factors related to changing lifestyle patterns.
Materials and Methods
This study collected stool samples from newly diagnosed (ND)–ENKTL patients (n=40) and conducted whole genome shotgun sequencing.
Results
ND-ENKTL revealed reduced alpha diversity in ND-ENKTL compared to healthy controls (HCs) (p=0.008), with Enterobacteriaceae abundance significantly contributing to the beta diversity difference between ENKTL and HCs (p < 0.001). Functional analysis indicated upregulated aerobic metabolism and degradation of aromatic compounds in ND-ENKTL. Enterobacteriaceae were associated not only with clinical data explaining disease status (serum C-reactive protein, stage, prognosis index of natural killer cell lymphoma [PINK], and PINK-E) but also with clinical outcomes (early relapse and short progression-free survival). The relative abundance of Enterobacteriaceae at the family level was similar between ENKTL and diffuse large B-cell lymphoma (DLBCL) (p=0.140). However, the ENKTL exhibited a higher abundance of Escherichia, in contrast to the prevalence of Enterobacter and Citrobacter in DLBCL. Linear regression analysis demonstrated a significant association between Escherichia abundance and programmed cell death-ligand-1 (PD-L1) levels in tissue samples (p=0.025), whereas no correlation with PD-L1 was observed for Enterobacteriaceae at the family level (p=0.571).
Conclusion
ND-ENKTL exhibited an abundance of Enterobacteriaceae and a dominant presence of Escherichia. These microbial characteristics correlated with disease status, treatment outcomes, and PD-L1 expression, suggesting the potential of the ENKTL microbiome as a biomarker and cause of lymphomagenesis, which warrants further exploration.

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Assessing the Efficacy of Bortezomib and Dexamethasone for Induction and Maintenance Therapy in Relapsed/Refractory Cutaneous T-Cell Lymphoma: A Phase II CISL1701/BIC Study: Yoon Seok Choi, Joonho Shim, Ka-Won Kang, Sang Eun Yoon, Jun Sik Hong, Sung Nam Lim, Ho-Young Yhim, Jung Hye Kwon, Gyeong-Won Lee, Deok-Hwan Yang, Sung Yong Oh, Ho-Jin Shin, Hyeon-Seok Eom, Dok Hyun Yoon, Hong Ghi Lee, Seong Hyun Jeong, Won Seog Kim, Seok Jin Kim; Cancer Res Treat. 2025;57(1):267-279. Published online July 16, 2024; DOI: https://doi.org/10.4143/crt.2024.479

Abstract PDF Supplementary Material PubReader ePub: Purpose
This multicenter, open-label, phase II trial evaluated the efficacy and safety of bortezomib combined with dexamethasone for the treatment of relapsed/refractory cutaneous T-cell lymphoma (CTCL) in previously treated patients across 14 institutions in South Korea.
Materials and Methods
Between September 2017 and July 2020, 29 patients with histologically confirmed CTCL received treatment, consisting of eight 4-week cycles of induction therapy followed by maintenance therapy, contingent upon response, for up to one year. The primary endpoint was the proportion of patients achieving an objective global response.
Results
Thirteen of the 29 patients (44.8%) achieved an objective global response, including two complete responses. The median progression-free survival (PFS) was 5.8 months, with responders showing a median PFS of 14.0 months. Treatment-emergent adverse events were generally mild, with a low incidence of peripheral neuropathy and hematologic toxicities. Despite the trend toward shorter PFS in patients with higher mutation burdens, genomic profiling before and after treatment showed no significant emergence of new mutations indicative of disease progression.
Conclusion
This study supports the use of bortezomib and dexamethasone as a viable and safe treatment option for previously treated CTCL, demonstrating substantial efficacy and manageability in adverse effects. Further research with a larger cohort is suggested to validate these findings and explore the prognostic value of mutation profiles.

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Pediatric cancer

The Effect of Hematopoietic Stem Cell Transplantation on Treatment Outcome in Children with Acute Lymphoblastic Leukemia: Hee Young Ju, Na Hee Lee, Eun Sang Yi, Young Bae Choi, So Jin Kim, Ju Kyung Hyun, Hee Won Cho, Jae Kyung Lee, Ji Won Lee, Ki Woong Sung, Hong Hoe Koo, Keon Hee Yoo; Cancer Res Treat. 2025;57(1):240-249. Published online July 5, 2024; DOI: https://doi.org/10.4143/crt.2024.155

Abstract PDF PubReader ePub: Purpose
Hematopoietic stem cell transplantation (HSCT) has been an important method of treatment in the advance of pediatric acute lymphoblastic leukemia (ALL). The indications for HSCT are evolving and require updated establishment. In this study, we aimed to investigate the efficacy of HSCT on the treatment outcome of pediatric ALL, considering the indications for HSCT and subgroups.
Materials and Methods
A retrospective analysis was conducted on ALL patients diagnosed and treated at a single center. Risk groups were categorized based on age at diagnosis, initial white blood cell count, disease lineage (B/T), and cytogenetic study results. Data on the patients’ disease status at HSCT and indications of HSCT were collected. Indications for HSCT were categorized as upfront HSCT at 1st complete remission, relapse, and refractory disease.
Results
Among the 549 screened patients, a total of 418 patients were included in the study; B-cell ALL (n=379) and T-cell ALL (T-ALL) (n=39). HSCT was conducted on a total of 106 patients (25.4%), with a higher frequency as upfront HSCT in higher-risk groups and specific cytogenetics. The overall survival (OS) was significantly better when done upfront than in relapsed or refractory state in T-ALL patients (p=0.002). The KMT2A-rearranged ALL patients showed superior event-free survival (p=0.002) and OS (p=0.022) when HSCT was done as upfront treatment.
Conclusion
HSCT had a substantial positive effect in a specific subset of pediatric ALL. In particular, frontline HSCT for T-ALL and KMT2A-rearranged ALL offered a better prognosis than when HSCT was conducted in a relapsed or refractory setting.

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Gastrointestinal cancer

Effector Function Characteristics of Exhausted CD8+ T-Cell in Microsatellite Stable and Unstable Gastric Cancer: Dong-Seok Han, Yoonjin Kwak, Seungho Lee, Soo Kyung Nam, Seong-Ho Kong, Do Joong Park, Hyuk-Joon Lee, Nak-Jung Kwon, Hye Seung Lee, Han-Kwang Yang; Cancer Res Treat. 2024;56(4):1146-1163. Published online April 12, 2024; DOI: https://doi.org/10.4143/crt.2024.317

Abstract PDF PubReader ePub

Purpose
Gastric cancer exhibits molecular heterogeneity, with the microsatellite instability–high (MSI-H) subtype drawing attention for its distinct features. Despite a higher survival rate, MSI-H gastric cancer lack significant benefits from conventional chemotherapy. The immune checkpoint inhibitors, presents a potential avenue, but a deeper understanding of the tumor immune microenvironment of MSI-H gastric cancer is essential.
Materials and Methods
We explored the molecular characteristics of CD8+ T-cell subtypes in three MSI-H and three microsatellite stable (MSS) gastric cancer samples using single-cell RNA sequencing and spatial transcriptome analysis.
Results
In MSI-H gastric cancer, significantly higher proportions of effector memory T cell (Tem), exhausted T cell (Tex), proliferative exhausted T cell (pTex), and proliferative T cell were observed, while MSS gastric cancer exhibited significantly higher proportions of mucosal-associated invariant T cell and natural killer T cell. In MSI-H gastric cancer, Tex and pTex exhibited a significant upregulation of the exhaustion marker LAG3, as well as elevated expression of effector function markers such as IFNG, GZMB, GZMH, and GZMK, compared to those in MSS gastric cancer. The interferon γ (IFN-γ) signaling pathway of Tex and pTex was retained compared to those of MSS gastric cancer. The spatial transcriptome analysis demonstrates the IFN-γ signaling pathway between neighboring Tex and malignant cell, showcasing a significantly elevated interaction in MSI-H gastric cancer.
Conclusion
Our study reveals novel finding indicating that IFN-γ signaling pathway is retained in Tex and pTex of MSI-H gastric cancer, offering a comprehensive perspective for future investigations into immunotherapy for gastric cancer.

Citations

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Neurogranin facilitates maintaining the immunosuppressive state of hepatocellular carcinoma by promoting TGF-β1 secretion
Dongjie Ye, Zhu Zhang, Yuxin Yao, Banglun Pan, Hao Wu, Xinyu Zhang, Xiaoqian Wang, Nanhong Tang
International Journal of Biological Macromolecules.2025; 311: 143716. CrossRef
T-cell senescence: Unlocking the tumor immune “Dark Box” - A multidimensional analysis from mechanism to tumor immunotherapeutic intervention
Jia Cheng, Jian Zheng, Chen Ma, Yongzhang Li, Hua Hao
Seminars in Cancer Biology.2025; 113: 190. CrossRef
Hybrid model for predicting microsatellite instability in colorectal cancer using hematoxylin & eosin-stained images and clinical features
Hangping Wei, Xiaowei Zhang, Zhen Zhou, Jianbin Xie, Weidong Han, Xiaofang Dong
Frontiers in Oncology.2025;[Epub] CrossRef
Simvastatin induces ferroptosis and activates anti-tumor immunity to sensitize anti-PD-1 immunotherapy in microsatellite stable gastric cancer
Yumei Ning, Shilin Fang, Runan Zhang, Jun Fang, Kun Lin, Yang Ding, Haihang Nie, Jingkai Zhou, Qiu Zhao, Hengning Ke, Haizhou Wang, Fan Wang
International Immunopharmacology.2024; 142: 113244. CrossRef

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Hematologic malignancy

Assessment of Bone Marrow Involvement in Extranodal NK/T-Cell Lymphoma: Positron Emission Tomography versus Bone Marrow Biopsy, and the Significance of Minimal Involvement by EBV+ Cells (KROG 18-09): Tae Hoon Lee, Hyun Ju Kim, Jong Hoon Lee, Jeongshim Lee, Jin Hee Kim, Dongryul Oh, Keun-Yong Eom; Cancer Res Treat. 2024;56(2):688-696. Published online December 11, 2023; DOI: https://doi.org/10.4143/crt.2023.1049

Abstract PDF PubReader ePub

Purpose
This study aims to investigate the diagnostic significance of positron emission tomography/computed tomography (PET/CT) in assessing bone marrow (BM) involvement through a comparison of PET/CT findings with BM biopsy in extranodal natural killer/T-cell lymphoma.
Materials and Methods
The medical records of 193 patients were retrospectively reviewed. Patients were categorized as having early-stage (PET-ES) or advanced-stage (PET-AS) disease based on PET/CT results. The BM involvement was classified into three groups according to BM biopsy: gross BM involvement, minimal BM involvement (defined as the presence of a limited number of Epstein-Barr virus–positive cells in BM), and no involvement. Calculations of the accuracy of PET/CT in detecting BM involvement and analysis of the clinical outcomes (progression-free survival [PFS] and overall survival [OS]) according to the BM biopsy status were performed.
Results
PET/CT exhibited a sensitivity of 64.7% and a specificity of 96.0% in detecting gross BM involvement. For detecting any (both gross and minimal) BM involvement, the sensitivity was 30.4%, while the specificity was 99.0%. Only one patient (0.7%) demonstrated gross BM involvement among the PET-ES group. Survival outcomes of the PET-ES group with minimal BM involvement (3-year PFS, 55.6%; OS, 77.0%) were closer to those of the PET-ES group with no BM involvement (3-year PFS, 62.2%; OS, 80.6%) than to those of the PET-AS group (3-year PFS, 20.1%; OS, 29.9%).
Conclusion
PET/CT exhibits high specificity, but moderate and low sensitivity in detecting gross and minimal BM involvement, respectively. The clinical significance of minimal BM involvement for patients in the PET-ES group may be limited.

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Magnetic Resonance Imaging and [18F]‐Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography‐Guided Therapy Improves Survival in Upper Aerodigestive Tract NK/T‐Cell Lymphoma, Nasal Type: A Prospective Cohort Study
Quanguang Ren, Yue Cui, He Huang, Xueying Li, Huangming Hong, Zhao Wang, Xiaojie Fang, Chengcheng Guo, Yuyi Yao, Zegeng Chen, Ying Huang, Zhiming Li, Qingqing Cai, Ying Tian, Hanyu Wang, Xiaoping Lin, Wei Fan, Lie Zheng, Suxia Lin, Ying Guo, Tongyu Lin
Head & Neck.2025;[Epub] CrossRef

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Pembrolizumab for Patients with Relapsed or Refractory Extranodal NK/T-Cell Lymphoma in Korea: Ji Yun Lee, Ji Hyun Kwon, Joon Young Hur, Jun Ho Yi, Ji Hyun Lee, Hyungwoo Cho, Young Rok Do, Jae-Cheol Jo, Hye Jin Kang, Yougil Koh, Won Sik Lee, Sung Nam Lim, Sang Eun Yoon, Seok Jin Kim, Jeong-Ok Lee; Cancer Res Treat. 2024;56(2):681-687. Published online November 10, 2023; DOI: https://doi.org/10.4143/crt.2023.1042

Abstract PDF PubReader ePub

Purpose
Programmed death-1 blockade with pembrolizumab has shown promising activity in relapsed/refractory (R/R) extranodal natural killer/T-cell lymphoma (NKTCL), but studies are limited, with small patient numbers.
Materials and Methods
Thirteen institutes involved with the Consortium for Improving Survival of Lymphoma, a Korean lymphoma study group, collected the clinical data of 59 patients treated with pembrolizumab as salvage therapy between 2016 and 2022.
Results
The median age of the patients was 60 years (range, 22 to 87 years), and 76.3% had advanced Ann Abor stage disease. Pembrolizumab was given to 35.6%, 40.7%, and 23.7% of the patients as second-, third-, and fourth- or higher-line chemotherapy, respectively. The overall response rate was 40.7%, with 28.8% having complete response. The estimated 2-year progression-free survival (PFS) and overall survival rates for all patients were 21.5% and 28.7%, respectively; for responders, the rates were 53.0% and 60.7%, respectively. Although not statistically significant, Eastern Cooperative Oncology Group performance status ≥ 2 (hazard ratio [HR], 1.91; 95% confidence interval [95% CI], 0.93 to 3.94; p=0.078) and stage III or IV disease (HR, 2.59; 95% CI, 0.96 to 6.96; p=0.060) were associated with a trend toward shorter PFS in multivariate analysis. Grade 3 or 4 adverse events (AEs) were noted in 12 patients (20.3%); neutropenia (10.2%), fatigue (6.8%), and pneumonitis (5.1%) were most common AEs.
Conclusion
In conclusion, while pembrolizumab had a modest effect on patients with R/R NKTCL, it may be a useful salvage therapy for patients with localized disease and good performance status.

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An evaluation of sugemalimab for the treatment of relapsed or refractory extranodal natural killer T-cell lymphoma
Yingfang Feng, Xia Liu, Jingwei Yu, Zheng Song, Lanfang Li, Lihua Qiu, Shiyong Zhou, Zhengzi Qian, Xianhuo Wang, Huilai Zhang
Expert Opinion on Biological Therapy.2025; 25(1): 9. CrossRef
Early growth response 1 as a key regulator of PD-L1 expression and immune evasion in extranodal NK/T-cell lymphoma
Ji Yun Lee, Kui-Jin Kim, Woochan Park, Jeongmin Seo, Minsu Kang, Eun Hee Jung, Sang-A Kim, Koung Jin Suh, Ji-Won Kim, Se Hyun Kim, Jeong-Ok Lee, Jin Won Kim, Yu Jung Kim, Keun-Wook Lee, Jee Hyun Kim, Soo-Mee Bang, Tae Min Kim, Jin Ho Paik
Blood Cancer Journal.2025;[Epub] CrossRef
Pembrolizumab

Reactions Weekly.2024; 2025(1): 390. CrossRef

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Impact of T-Cell Engagers on COVID-19–Related Mortality in B-Cell Lymphoma Patients Receiving B-Cell Depleting Therapy: Chan Mi Lee, Pyoeng Gyun Choe, Chang Kyung Kang, Hyeon Jae Jo, Nam Joong Kim, Sung-Soo Yoon, Tae Min Kim, Wan Beom Park, Myoung-don Oh; Cancer Res Treat. 2024;56(1):324-333. Published online July 6, 2023; DOI: https://doi.org/10.4143/crt.2023.738

Abstract PDF Supplementary Material PubReader ePub

Purpose
B-cell depleting therapies, including T-cell engager (TCE), are increasingly used for patients with hematologic malignancies, including during the coronavirus disease 2019 (COVID-19) pandemic. We aimed to evaluate the relationship between TCE therapy and COVID-19–related outcomes among patients with COVID-19 and B-cell lymphomas receiving B-cell depleting therapy.
Materials and Methods
This retrospective cohort study included patients with B-cell lymphoma, who were admitted to Seoul Natio-nal University Hospital with COVID-19 between September 2021 and February 2023, and received B-cell depleting therapy before COVID-19 diagnosis. Multivariable logistic regression was used to identify factors associated with severe to critical COVID-19 and COVID-19–related mortality.
Results
Of 54 patients with B-cell lymphomas and COVID-19 who received B-cell depleting therapy, 14 were treated with TCE (TCE group) and 40 with rituximab (RTX group). COVID-19–related mortality was higher in the TCE group than in the RTX group (57.1% vs. 12.5%, p=0.002). In multivariable analyses, TCE therapy (adjusted odds ratio [aOR], 7.08; 95% confidence interval [CI], 1.29 to 38.76; p=0.024) and older age (aOR, 1.06; 95% CI, 1.00 to 1.13; p=0.035) were associated with severe to critical COVID-19. TCE therapy (aOR, 8.98; 95% CI, 1.48 to 54.40; p=0.017), older age (aOR, 1.13; 95% CI, 1.02 to 1.26; p=0.022), and prior bendamustine therapy (aOR, 7.78; 95% CI, 1.17 to 51.65; p=0.034) were independent risk factors for COVID-19–related mortality.
Conclusion
B-cell lymphoma patients treated with TCE had significantly worse outcomes from COVID-19 than those treated with RTX. TCE therapy should be used with caution in B-cell lymphoma patients during the COVID-19 epidemic.

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Epcoritamab plus GemOx in transplant-ineligible relapsed/refractory DLBCL: results from the EPCORE NHL-2 trial
Joshua D. Brody, Judit Jørgensen, David Belada, Régis Costello, Marek Trněný, Umberto Vitolo, David John Lewis, Yasmin H. Karimi, Anna Sureda, Marc André, Björn E. Wahlin, Pieternella J. Lugtenburg, Tony Jiang, Kubra Karagoz, Andrew J. Steele, Aqeel Abbas
Blood.2025; 145(15): 1621. CrossRef
Long-Term Outcomes of COVID-19 and Risk Factors for Prolonged or Persistent COVID-19 in Lymphoma Patients: A Multicenter, Retrospective Cohort Study
Jung Ah Lee, Min Han, Sangmin Ahn, Yongseop Lee, Joon-Sup Yeom, Jun Yong Choi, Nam Su Ku, Su Jin Jeong, Jung Ho Kim, Jin Seok Kim, Haerim Chung, Hyunsoo Cho, Yu Ri Kim, Jin Young Ahn
Journal of Korean Medical Science.2024;[Epub] CrossRef
Features of the T-cell immune response in patients with hematological diseases after SARS-CoV-2 infection and vaccination
K. V. Zornikova, N. O. Ivanova, O. A. Aleshina, S. A. Sheetikov, V. D. Davydova, A. V. Bogolyubova
Russian journal of hematology and transfusiology.2024; 69(2): 200. CrossRef
Call for Balancing the Risks and Benefits of Immunotherapeutic Agents for Lymphoma during the COVID-19 Pandemic
Chan Mi Lee, Wan Beom Park
Infection & Chemotherapy.2024; 56(3): 406. CrossRef
Epcoritamab in relapsed/refractory large B-cell lymphoma: 2-year follow-up from the pivotal EPCORE NHL-1 trial
Catherine Thieblemont, Yasmin H. Karimi, Herve Ghesquieres, Chan Y. Cheah, Michael Roost Clausen, David Cunningham, Wojciech Jurczak, Young Rok Do, Robin Gasiorowski, David John Lewis, Tae Min Kim, Marjolein van der Poel, Michelle Limei Poon, Tatyana Feld
Leukemia.2024; 38(12): 2653. CrossRef

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Case Report

Long-term Complete Remission of Decitabine-Primed Tandem CD19/CD22 CAR-T Therapy with PD-1 and BTK Inhibitors Maintenance in a Refractory Primary Central Nervous System Lymphoma Patient: Rui Zou, Xiao Zhou, Hailing Liu, Peng Wang, Fan Xia, Liqing Kang, Lei Yu, Depei Wu, Zhengming Jin, Changju Qu; Cancer Res Treat. 2023;55(4):1363-1368. Published online June 14, 2023; DOI: https://doi.org/10.4143/crt.2023.371

Abstract PDF PubReader ePub

Primary central nervous system lymphoma (PCNSL) is a rare and aggressive non-Hodgkin’s lymphoma that affects the brain, eyes, cerebrospinal fluid, or spinal cord without systemic involvement. The outcome of patients with PCNSL is worse compared to patients with systemic diffuse large B-cell lymphoma. Given potential mortality associated with severe immune effector cell-associated neurotoxicity syndrome (ICANS), patients with PCNSL have been excluded from most clinical trials involving chimeric antigen receptor T-cell (CAR-T) therapy initially. Here, we report for the first time to apply decitabine-primed tandem CD19/CD22 dual-targeted CAR-T therapy with programmed cell death-1 (PD-1) and Bruton’s tyrosine kinase (BTK) inhibitors maintenance in one patient with multiline-resistant refractory PCNSL and the patient has maintained complete remission (CR) for a 35-month follow-up period. This case represents the first successful treatment of multiline resistant refractory PCNSL with long-term CR and without inducing ICANS under tandem CD19/CD22 bispecific CAR-T therapy followed by maintenance therapy with PD-1 and BTK inhibitors. This study shows tremendous potential in the treatment of PCNSL and offers a look toward ongoing clinical studies.

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CAR-T cell therapy in the treatment of relapsed or refractory primary central nervous system lymphoma: recent advances and challenges
Shuzhen Xiong, Shuni Zhang, Ningning Yue, Jiajia Cao, Chongyang Wu
Leukemia & Lymphoma.2025; 66(6): 1045. CrossRef
New hopes and challenges in targeted therapy and immunotherapy for primary central nervous system lymphoma
Chuanwei Yang, Xiaohui Ren, Yong Cui, Haihui Jiang, Ming Li, Kefu Yu, Shaoping Shen, Mingxiao Li, Xiaokang Zhang, Xuzhe Zhao, Qinghui Zhu, Xingyao Bu, Song Lin
Frontiers in Immunology.2025;[Epub] CrossRef
Are we ready for personalizedCAR‐Ttherapy?
Anna Strzelec, Grzegorz Helbig
European Journal of Haematology.2024; 112(2): 174. CrossRef
Tislelizumab augment the efficacy of CD19/22 dual‐targeted chimeric antigen receptor T cell in advanced stage relapsed or refractory B‐cell non‐Hodgkin lymphoma
Ying Zhang, Hongzhi Geng, Liangyu Zeng, Jiaqi Li, Qin Yang, Sixun Jia, Xiangping Zong, Wenzhi Cai, Shuangzhu Liu, Yutong Lu, Lei Yu, Caixia Li, Depei Wu
Hematological Oncology.2024;[Epub] CrossRef
Therapeutic targeting of DNA methylation alterations in cancer
Abigail V. Lee, Kevin A. Nestler, Katherine B. Chiappinelli
Pharmacology & Therapeutics.2024; 258: 108640. CrossRef
Cytarabine/methotrexate/rituximab

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A systematic review of primary central nervous system lymphoma
Lei Zhang, Qingyuan Zhang
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The synergistic immunotherapeutic impact of engineered CAR-T cells with PD-1 blockade in lymphomas and solid tumors: a systematic review
Bibhu Prasad Satapathy, Pooja Sheoran, Rohit Yadav, Dewan Chettri, Dhruba Sonowal, Chinmayee Priyadarsini Dash, Prachi Dhaka, Vivek Uttam, Ritu Yadav, Manju Jain, Aklank Jain
Frontiers in Immunology.2024;[Epub] CrossRef
Siglecs-mediated immune regulation in neurological disorders
Huifang Tu, Limei Yuan, Bo Ni, Yufeng Lin, Kaiyuan Wang
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Original Articles

Genitourinary cancer

Favorable Immunotherapy Plus Tyrosine Kinase Inhibition Outcome of Renal Cell Carcinoma Patients with Low CDK5 Expression: Xianglai Xu, Ying Wang, Zhaoyi Chen, Yanjun Zhu, Jiajun Wang, Jianming Guo; Cancer Res Treat. 2023;55(4):1321-1336. Published online April 3, 2023; DOI: https://doi.org/10.4143/crt.2022.1532

Abstract PDF Supplementary Material PubReader ePub

Purpose
Immunotherapy (IO) plus tyrosine kinase inhibitor (TKI) has become the first-line treatment for advanced renal cell carcinoma, despite the lack of prognostic biomarkers. Cyclin-dependent kinase 5 (CDK5) affects the tumor microenvironment, which may influence the efficacy of TKI+IO.
Materials and Methods
Two cohorts from our center (Zhongshan Metastatic Renal Cell Carcinoma [ZS-MRCC] cohort, Zhongshan High-risk Localized Renal Cell Carcinoma [ZS-HRRCC] cohort) and one cohort from a clinical trial (JAVELIN-101) were enrolled. The expression of CDK5 of each sample was determined by RNA sequencing. Immune infiltration and T cell function were evaluated by flow cytometry and immunohistochemistry. Response and progression-free survival (PFS) were set as primary endpoints.
Results
Patients of low CDK5 expression showed higher objective response rate (60.0% vs. 23.3%) and longer PFS in both cohorts (ZS-MRCC cohort, p=0.014; JAVELIN-101 cohort, p=0.040). CDK5 expression was enhanced in non-responders (p < 0.05). In the ZS-HRRCC cohort, CDK5 was associated with decreased tumor-infiltrating CD8+ T cells, which was proved by immunohistochemistry (p < 0.05) and flow cytometry (Spearman’s ρ=–0.49, p < 0.001). In the high CDK5 subgroup, CD8+ T cells revealed a dysfunction phenotype with decreased granzyme B, and more regulatory T cells were identified. A predictive score was further constructed by random forest, involving CDK5 and T cell exhaustion features. The RFscore was also validated in both cohorts. By utilizing the model, more patients might be distinguished from the overall cohort. Additionally, only in the low RFscore did TKI+IO outperform TKI monotherapy.
Conclusion
High-CDK5 expression was associated with immunosuppression and TKI+IO resistance. RFscore based on CDK5 may be utilized as a biomarker to determine the optimal treatment strategy.

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SPP1 expression indicates outcome of immunotherapy plus tyrosine kinase inhibition in advanced renal cell carcinoma
Xianglai Xu, Jinglai Lin, Jiahao Wang, Ying Wang, Yanjun Zhu, Jiajun Wang, Jianming Guo
Human Vaccines & Immunotherapeutics.2024;[Epub] CrossRef
Efficacy and Safety of Immuno-Oncology Plus Tyrosine Kinase Inhibitors as Late-Line Combination Therapy for Patients with Advanced Renal Cell Carcinoma
Shuzo Hamamoto, Yoshihiko Tasaki, Toshiharu Morikawa, Taku Naiki, Toshiki Etani, Kazumi Taguchi, Shoichiro Iwatsuki, Rei Unno, Tomoki Takeda, Takashi Nagai, Kengo Kawase, Yoshihisa Mimura, Yosuke Sugiyama, Atsushi Okada, Yoko Furukawa-Hibi, Takahiro Yasui
Journal of Clinical Medicine.2024; 13(12): 3365. CrossRef
PSMD2 overexpression as a biomarker for resistance and prognosis in renal cell carcinoma treated with immune checkpoint and tyrosine kinase inhibitors
Xianglai Xu, Jiahao Wang, Ying Wang, Yanjun Zhu, Jiajun Wang, Jianming Guo
Cellular Oncology.2024; 47(5): 1943. CrossRef
External validation of hemoglobin and neutrophil levels as predictors of the effectiveness of ipilimumab plus nivolumab for treating renal cell carcinoma
Shuzo Hamamoto, Yoshihiko Tasaki, Shimpei Yamashita, Junya Furukawa, Kazutoshi Fujita, Ryotaro Tomida, Makito Miyake, Noriyuki Ito, Hideto Iwamoto, Yosuke Sugiyama, Kazumi Taguchi, Takahiro Yasui
Frontiers in Oncology.2024;[Epub] CrossRef

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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

Abstract PDF Supplementary Material PubReader ePub

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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Angioimmunoblastic T-cell lymphoma: a concise overview encompassing the pathogenetic, pathological, clinical, therapeutical characteristics, and recent advances
Yan Feng, Yaxian Ma, Tongjuan Li, Min Liu, Zetong Hong, Qing Yin, Miao Zheng
Clinical and Experimental Medicine.2025;[Epub] CrossRef
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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A New Prognostic Index for Extranodal Natural Killer/T-Cell Lymphoma:Incorporation of Serum β-2 Microglobulin to PINK: Sora Kang, Hyungwoo Cho, Shin Kim, Kyoungmin Lee, Eun Hee Kang, Jung Sun Park, Yoon Sei Lee, Chan-Sik Park, Heounjeong Go, Jooryung Huh, Jin Sook Ryu, Sang-Wook Lee, Seok Jin Kim, Won Seog Kim, Sang Eun Yoon, Young Hyeh Ko, Cheolwon Suh; Cancer Res Treat. 2023;55(1):314-324. Published online March 31, 2022; DOI: https://doi.org/10.4143/crt.2022.015

Abstract PDF Supplementary Material PubReader ePub

Purpose
Prognostic Index for Natural Killer Lymphoma (PINK) is the most widely accepted prognostic model for patients withextranodal natural killer/T-cell lymphoma (ENKTL) treated with non-anthracycline–based therapy. We aimed to evaluate the prognostic implications of serum β-2 microglobulin (β2M) in the context of PINK and proposed a new prognostic model.
Materials and Methods
A total of 138 patients who were newly diagnosed with ENKTL and treated with non-anthracycline-based chemotherapy were identified. The cut-off value of high serum β2M was calculated by maximal-chi square methods (4.1 mg/L). A new prognostic model incorporating serum β2M into PINK was proposed and validated in an independent validation cohort (n=88).
Results
The patients’ median age was 53.5 years (range, 19 to 80 years). Patients with high serum β2M levels had significantly worse overall survival (OS) and progression-free survival (PFS). In multivariate analysis, high serum β2M was an independent adverse prognostic factor for OS. A new PINK-B (Prognostic Index for Natural Killer Lymphoma-serum β-2 microglobulin) model stratifiedpatients into three groups with distinct OS and PFS in the training cohort (3-year OS, 84.1% [95% confidence interval, 75.1 to 94.2], 46.8% [36.1 to 60.8] and 17.6% [6.3 to 49.2] for the low-, intermediate, and high-risk groups, respectively; 3-year PFS, 70.6% [59.4 to 83.8], 35.9% [25.9 to 49.8], and 7.35% [1.1 to 46.7] for the low-, intermediate-, and high-risk groups, respectively). The PINK-B model was further validated in an independent cohort.
Conclusion
Serum β2M is an independent prognostic factor for ENKTL patients. The new serum β2M-based prognostic model may be useful for identifying ultra-high-risk patients, and it can easily be adopted into daily clinical practice.

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Beta-2 microglobulin in lymphoma
Gaurav Gupta, Muhammad Afzal, Ahsas Goyal, G. PadmaPriya, Manish Srivastava, Kattela Chennakesavulu, Biswaranjan Mohanty, A. Rekha, Avijit Mazumder, Kavita Goyal, Haider Ali, Moyad Shahwan
Clinica Chimica Acta.2025; 576: 120418. CrossRef
Elevated serum IL-6 and total IgEAb are associated with poor survival in natural killer/T-cell lymphoma
Yun Hui, Yingjun Gao, Jiawei Li, Qingtao Kong, Yuanyuan Duan, Haibo Liu, Fang Liu, Hong Sang
Annals of Hematology.2024; 103(4): 1285. CrossRef
Prognostic Impact of Serum β2-Microglobulin Levels in Hodgkin Lymphoma Treated with ABVD or Equivalent Regimens: A Comprehensive Analysis of 915 Patients
Theodoros P. Vassilakopoulos, Maria Arapaki, Panagiotis T. Diamantopoulos, Athanasios Liaskas, Fotios Panitsas, Marina P. Siakantaris, Maria Dimou, Styliani I. Kokoris, Sotirios Sachanas, Marina Belia, Chrysovalantou Chatzidimitriou, Elianna A. Konstantin
Cancers.2024; 16(2): 238. CrossRef
Prognostic Value of18F-FDG PET/CT Radiomics in Extranodal Nasal-Type NK/T Cell Lymphoma
Yu Luo, Zhun Huang, Zihan Gao, Bingbing Wang, Yanwei Zhang, Yan Bai, Qingxia Wu, Meiyun Wang
Korean Journal of Radiology.2024; 25(2): 189. CrossRef
A novel prognostic index for extranodal natural killer/T-cell lymphoma in the era of pegaspargase/L-asparaginase
Ziyuan Shen, Xudong Zhang, Yujie Li, Xicheng Chen, Xing Xing, Hao Zhang, Jingjing Ye, Ling Wang, Tao Jia, Taigang Zhu, Yuqing Miao, Chunling Wang, Hui Liu, Liang Wang, Wei Sang
Future Oncology.2024; 20(28): 2071. 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

Abstract PDF Supplementary Material PubReader ePub

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 B and T Cell Lymphomas: From Bench to Bedside
Mohammad Almasri, Nawar Maher, Bashar Al Deeban, Ndeye Marie Diop, Riccardo Moia, Gianluca Gaidano
International Journal of Molecular Sciences.2025; 26(10): 4869. CrossRef
Angioimmunoblastic T-cell lymphoma: a concise overview encompassing the pathogenetic, pathological, clinical, therapeutical characteristics, and recent advances
Yan Feng, Yaxian Ma, Tongjuan Li, Min Liu, Zetong Hong, Qing Yin, Miao Zheng
Clinical and Experimental Medicine.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

Abstract PDF PubReader ePub

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

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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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Hematologic Malignancy

Baseline Total Metabolic Tumor Volume and Total Lesion Glycolysis Measured on ¹⁸F-FDG PET-CT Predict Outcomes in T-Cell Lymphoblastic Lymphoma: Xiaoyan Feng, Xin Wen, Ling Li, Zhenchang Sun, Xin Li, Lei Zhang, Jingjing Wu, Xiaorui Fu, Xinhua Wang, Hui Yu, Xinran Ma, Xudong Zhang, Xinli Xie, Xingmin Han, Mingzhi Zhang; Cancer Res Treat. 2021;53(3):837-846. Published online December 2, 2020; DOI: https://doi.org/10.4143/crt.2020.123

Abstract PDF Supplementary Material PubReader ePub

Purpose
There is no optimal prognostic model for T-cell lymphoblastic lymphoma (T-LBL). Here, we discussed the predictive value of total metabolic tumor volume (TMTV) and total lesion glycolysis (TLG) measured on 18F-fluorodeoxyglucose positron emission tomography–computed tomography (PET-CT) in T-LBL.
Materials and Methods
Thirty-seven treatment naïve T-LBL patients with PET-CT scans were enrolled. TMTV was obtained using the 41% maximum standardized uptake value (SUVmax) threshold method, and TLG was measured as metabolic tumor volume multiplied by the mean SUV. Progression-free survival (PFS) and overall survival (OS) were analyzed by Kaplan-Meier curves and compared by the log-rank test.
Results
The optimal cutoff values for SUVmax, TMTV, and TLG were 12.7, 302 cm3, and 890, respectively. A high SUVmax, TMTV, and TLG indicated a shorten PFS and OS. On multivariable analysis, TMTV ≥ 302 cm3, and central nervous system (CNS) involvement predicted inferior PFS, while high SUVmax, TLG and CNS involvement were associated with worse OS. Subsequently, we generated a risk model comprising high SUVmax, TMTV or TLG and CNS involvement, which stratified the population into three risk groups, which had significantly different median PFS of not reached, 14 months, and 7 months for low-risk group, mediate-risk group, and high-risk group, respectively (p < 0.001). Median OS were not reached, 27 months, and 13 months, respectively (p < 0.001).
Conclusion
Baseline SUVmax, TMTV, and TLG measured on PET-CT are strong predictors of worse outcome in T-LBL. A risk model integrating these three parameters with CNS involvement identifies patients at high risk of disease progression.

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A novel prognostic model utilizing TMTV and SUVmax from 18F-FDG PET/CT for predicting overall survival in patients with extranodal NK/T- cell lymphoma
Hua Wang, Demei Feng, Yiwen Mo, Huangming Hong, Yingying Hu, Li Huang, Xiaolei Wei, Yajun Li, Haibin Huang, Runhui Zheng, Yonghua Li, Hui Zeng, Robert Peter Gale, Tian Ying, Jing Guo, Zhenshu Xu, Wei Fan, Tongyu Lin
BMC Cancer.2025;[Epub] CrossRef
Metabolic parameters predict survival and toxicity in chimeric antigen receptor T‐cell therapy‐treated relapsed/refractory large B‐cell lymphoma
Hazim S. Ababneh, Andrea K. Ng, Jeremy S. Abramson, Jacob D. Soumerai, Ronald W. Takvorian, Matthew J. Frigault, Chirayu G. Patel
Hematological Oncology.2024;[Epub] CrossRef
Diagnosis of bone marrow involvement in angioimmunoblastic T-cell lymphoma should be based on both [ 18 F]FDG-PET/CT and bone marrow biopsy findings
Xinyu Liang, Chunli Yang, Minggang Su, Liqun Zou
Current Medical Research and Opinion.2024; 40(5): 803. CrossRef
The Role of Pre-therapeutic 18F-FDG PET/CT in Pediatric Hemophagocytic Lymphohistiocytosis With Epstein-Barr Virus Infection
Xia Lu, Ang Wei, Xu Yang, Jun Liu, Siqi Li, Ying Kan, Wei Wang, Tianyou Wang, Rui Zhang, Jigang Yang
Frontiers in Medicine.2022;[Epub] CrossRef
Prognostic Value of Heterogeneity Index Derived from Baseline 18F-FDG PET/CT in Mantle Cell Lymphoma
Fei Liu, Bingxin Gu, Nan Li, Herong Pan, Wen Chen, Ying Qiao, Shaoli Song, Xiaosheng Liu
Frontiers in Oncology.2022;[Epub] CrossRef
Staging and response assessment of lymphoma: a brief review of the Lugano classification and the role of FDG-PET/CT
Kwai Han Yoo
Blood Research.2022; 57(S1): S75. CrossRef
Prediction of prognosis and pathologic grade in follicular lymphoma using 18F-FDG PET/CT
Hongyan Li, Min Wang, Yajing Zhang, Fan Hu, Kun Wang, Chenyang Wang, Zairong Gao
Frontiers in Oncology.2022;[Epub] CrossRef
PET/CT Evaluation of the Effect of Allogeneic Hematopoietic Stem Cell Transplantation in the Treatment of T‐Cell Lymphoblastic Lymphoma
Jin Zhao, Xiaojing Guo, Li Ma, Meijing Zheng, Tao Guan, Liping Su, Mohammad Farukh Hashmi
Contrast Media & Molecular Imaging.2022;[Epub] CrossRef
Clinical and prognostic role of 2-[18F]FDG PET/CT and sarcopenia in treatment-naïve patients with T-cell lymphoblastic lymphoma
Xiaoyue Tan, Hui Yuan, Dongjiang Li, Xiaolin Sun, Chongyang Ding, Lei Jiang
Annals of Hematology.2022; 101(12): 2699. CrossRef
Prognostic value of baseline total metabolic tumour volume of 18F-FDG PET/CT imaging in patients with angioimmunoblastic T-cell lymphoma
Huanyu Gong, Tiannv Li, Jianyong Li, Lijun Tang, Chongyang Ding
EJNMMI Research.2021;[Epub] CrossRef

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Characteristics, Prognostic Factors, and Survival of Patients with NK/T-Cell Lymphoma of Non-upper Aerodigestive Tract: A 17-Year Single-Center Experience: Ze-Long Liu, Xi-Wen Bi, Xue-Wen Zhang, De-Xin Lei, Pan-Pan Liu, Hang Yang, Yan Gao, Yuan-Xue Jiang, Wen-Qi Jiang, Yi Xia; Cancer Res Treat. 2019;51(4):1557-1567. Published online April 1, 2019; DOI: https://doi.org/10.4143/crt.2018.681

Abstract PDF Supplementary Material PubReader ePub

Purpose
The extranodal natural killer (NK)/T-cell lymphoma (NKTCL) of non-upper aerodigestive tract (NUAT) was found to have clinical heterogeneity compared with NKTCL of the upper aerodigestive tract (UAT) in small scale studies. We conducted this study in a much larger cohort to analyze the clinical characteristics, prognostic factors, treatment modality, and clinical outcomes of patients with NUAT-NKTCL.
Materials and Methods
From January 2001 to December 2017, a total of 757 NKTCL patients were identified and included in this study, including 92 NUAT-NKTCL patients (12.2%) and 665 UAT-NKTCL patients (87.8%).
Results
NUAT-NKTCL patients had relatively poorer performance status, more unfavorable prognostic factors, and more advanced stage, compared with UAT-NKTCL patients. The 5-year overall survival (OS) was 34.7% for NUAT-NKTCL, which was significantly worse than UAT-NKTCL (64.2%, p<0.001). The median OS duration was 30.9 months for NUAT-NKTCL. Multivariate analysis showed that presence with B symptoms and elevated serum lactate dehydrogenase independently predicted worse OS. International prognostic index score and prognostic index of natural killer lymphoma score still had prognostic values in NUAT-NKTCL, while the Ann Arbor system could not accurately predict the OS.
Conclusion
NUAT-NKTCL is a distinctive subtype of NKTCL in many aspects. Patients with NUAT-NKTCL have relatively poorer performance status, more unfavorable prognostic factors, more advanced stage, and poorer prognosis.

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Magnetic Resonance Imaging and [18F]‐Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography‐Guided Therapy Improves Survival in Upper Aerodigestive Tract NK/T‐Cell Lymphoma, Nasal Type: A Prospective Cohort Study
Quanguang Ren, Yue Cui, He Huang, Xueying Li, Huangming Hong, Zhao Wang, Xiaojie Fang, Chengcheng Guo, Yuyi Yao, Zegeng Chen, Ying Huang, Zhiming Li, Qingqing Cai, Ying Tian, Hanyu Wang, Xiaoping Lin, Wei Fan, Lie Zheng, Suxia Lin, Ying Guo, Tongyu Lin
Head & Neck.2025;[Epub] CrossRef
Clinical features, prognostic stratification, and treatment of advanced-stage non-nasal type extranodal natural killer/T-cell lymphoma: a multi-institutional real-world study
Yu-Ce Wei, Wei-Xin Liu, Fei Qi, Chang-Gong Zhang, Bao-Min Zheng, Yan Xie, Bo Chen, Di Zhang, Wei-Ping Liu, Hui Fang, Yue Chai, Shu-Nan Qi, Ye-Xiong Li, Wei-Hu Wang, Yu-Qin Song, Jun Zhu, Mei Dong
Annals of Hematology.2024; 103(1): 163. CrossRef
Genomic features reveal potential benefit of adding anti-PD-1 immunotherapy to treat non-upper aerodigestive tract natural killer/T-cell lymphoma
Zegeng Chen, He Huang, Huageng Huang, Le Yu, Huawei Weng, Jian Xiao, Liqun Zou, Huilai Zhang, Chaoyong Liang, Hui Zhou, Hongqiang Guo, Zhao Wang, Zhiming Li, Tao Wu, Hongyu Zhang, Huijing Wu, Zhigang Peng, Linzhu Zhai, Xinggui Chen, Yang Liang, Huangming
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Jun CAI, Yi CAO, LiYun QIU, Yan GAO, HuiQiang HUANG, QingQing CAI
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Yang Chunli, Jiang Ming, Ma Ziyan, Ji Jie, Lv Shuli, Huang Jie, Wu Yu, Xu Caigang, Zou Liqun
Cancer Medicine.2023; 12(3): 2614. CrossRef
Diagnostic and prognostic value of pretreatment PET/CT in extranodal natural killer/T-cell lymphoma: a retrospective multicenter study
Mingjie Yu, Zegeng Chen, Zhao Wang, Xiaojie Fang, Xi Li, Haimei Ye, Tongyu Lin, He Huang
Journal of Cancer Research and Clinical Oncology.2023; 149(11): 8863. CrossRef
Comparative analysis of upper aerodigestive tract and non-upper aerodigestive tract in NK/T-cell lymphoma
Xiaohong Liu, Dedong Cao, Hui Liu, XiaoKang Ke, Xin Liu, Ximing Xu
Clinical and Translational Oncology.2023; 26(1): 214. CrossRef
Intensive therapy can improve long‐term survival in newly diagnosed, advanced‐stage extranodal NK/T‐cell lymphoma: A multi‐institutional, real‐world study
Yu‐Ce Wei, Fei Qi, Bao‐Min Zheng, Chang‐Gong Zhang, Yan Xie, Bo Chen, Wei‐Xin Liu, Wei‐Ping Liu, Hui Fang, Shu‐Nan Qi, Di Zhang, Yue Chai, Ye‐Xiong Li, Wei‐Hu Wang, Yu‐Qin Song, Jun Zhu, Mei Dong
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A retrospective study on the clinicopathological and molecular features of 22 cases of natural killer/T-cell lymphoma in children and adolescents
Guan‑Nan Wang, Wu‑Gan Zhao, Xu-Dong Zhang, Xiang-Yu Jian, Chong-Li Zhang, Ming-Zhi Zhang, Wen‑Cai Li
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Comparison analysis of first-line asparaginase- versus non-asparaginase-based regimens for early-stage extranodal NK/T-cell lymphoma
Fei Qi, Yan Xie, Dedao Wang, Yue Chai, Bo Chen, Yan Sun, Weiping Liu, Shunan Qi, Yuce Wei, Hui Fang, Dan Zhao, Lin Gui, Yong Yang, Xiaoli Feng, Ning Ding, Lan Mi, Shaokun Shu, Yexiong Li, Yuqin Song, Mei Dong, Jun Zhu
Annals of Hematology.2022; 101(9): 2021. CrossRef

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Circulating Low Absolute CD4⁺ T Cell Counts May Predict Poor Prognosis in Extranodal NK/T-Cell Lymphoma Patients Treating with Pegaspargase-Based Chemotherapy: Ya-Ping Zhang, Run Zhang, Hua-Yuan Zhu, Li Wang, Yu-Jie Wu, Jin-Hua Liang, Wen-Yu Shi, Hong Liu, Wei Xu, Jian-Yong Li; Cancer Res Treat. 2019;51(1):368-377. Published online May 14, 2018; DOI: https://doi.org/10.4143/crt.2018.010

Abstract PDF PubReader ePub

Purpose
Extranodal natural killer/T-cell lymphoma, nasal type (ENKTL) is a rare subtype of non-Hodgkin lymphoma, and asparaginase-based regimens are the best first-line treatments. Data on the role of specific circulating lymphocyte subsets in the progression of ENKTL are limited. The aim of this study was to investigate the clinical correlation and distribution of circulating absolute CD4+ T-cell counts (ACD4Cs) in ENKTL.
Materials and Methods
We retrospectively searched medical records for 70 newly diagnosed ENKTL patients treated with pegaspargase-based regimens. Comparison of ACD4Cs as a continuous parameter in different groups was calculated. Univariate and multivariate analyses were used to assess prognostic factors for overall survival (OS) and progression-free survival (PFS).
Results
Stage III/IV, B symptoms, elevated lactate dehydrogenase, monocytopenia, high-intermediate and high risk International Prognostic Index (IPI) and Korean Prognostic Index (KPI), high risk Prognostic Index of Natural Killer Lymphoma (PINK), and lower lymphocytes were significantly associated with low ACD4C at diagnosis. With a median follow-up time of 32 months, patients who had an ACD4C < 0.30×109/L had a worse OS. Median OS was 11 months and median PFS was 5 months in the low ACD4C cohort. There were significant differences in both OS and PFS between the two cohorts. Moreover, multivariate Cox analysis identified ACD4Cs as an independent predictor for OS and PFS.
Conclusion
Low ACD4Cs were associated with poorer survival and could act as a negative predictor for ENKTL patients treated with asparaginase-based regimens.

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Prognostic Value of Peripheral Blood Lymphocyte Subsets in Children and Adolescents With High‐Grade Mature B‐Cell Non‐Hodgkin Lymphoma: A Real‐World Outcomes Study
Chenggong Zeng, Zhiqing Wei, Junting Huang, Jia Zhu, Feifei Sun, Juan Wang, Suying Lu, Yizhuo Zhang, Xiaofei Sun, Zijun Zhen
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Low levels of CD3 + and CD8 + T cells in peripheral blood can predict poor efficacy of first-line chemotherapy in patients with angioimmunoblastic T cell lymphoma
Yanfei Liu, Weiwei Song, Yuqin Song, Jun Zhu, Yan Xie
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Prognostic Significance of Circulating Immune Subset Counts in Nasopharyngeal Carcinoma
Honghui Xie, Lin Zhang, Lizhi Chen, Wenchao Zhou, Lijuan Zhang, Yong Su, Bocheng Li, Peng Ding, Yun Xiao, Tianzhu Lu, Xiaochang Gong, Jingao Li
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Yaxiao Lu, Jingwei Yu, Wenchen Gong, Liping Su, Xiuhua Sun, Ou Bai, Hui Zhou, Xue Guan, Tingting Zhang, Lanfang Li, Lihua Qiu, Zhengzi Qian, Shiyong Zhou, Bin Meng, Xiubao Ren, Xianhuo Wang, Huilai Zhang
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Towards Next Generation Biomarkers in Natural Killer/T-Cell Lymphoma
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Life.2021; 11(8): 838. CrossRef
The predictive value of dynamic monitoring of peripheral blood lymphocyte to monocyte ratio in patients with extranodal NK/T cell lymphoma
Shengnan Zhang, Mengjuan Li, Fangfang Yuan, Lin Chen, Ruihua Mi, Xudong Wei, Yongping Song, Qingsong Yin
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Jonathan Moreira, Leonidas C. Platanias, Kehinde U. A. Adekola
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The combined prognostic value of pretreatment neutrophil-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, and platelet-to-lymphocyte ratio in stage IE/IIE extranodal natural killer/T-cell lymphoma
Xiaoying Quan
Oncology and Translational Medicine.2019; : 137. CrossRef

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The Prognostic Role of Circulating Epstein-Barr Virus DNA Copy Number in Angioimmunoblastic T-Cell Lymphoma Treated with Dose-Adjusted EPOCH: Jin-Hua Liang, Luo Lu, Hua-Yuan Zhu, Wang Li, Lei Fan, Jian-Yong Li, Wei Xu; Cancer Res Treat. 2019;51(1):150-157. Published online April 2, 2018; DOI: https://doi.org/10.4143/crt.2017.476

Abstract PDF PubReader ePub

Purpose
Determine the frequency and prognostic value of circulating Epstein-Barr virus (EBV) DNA copy number in angioimmunoblastic T-cell lymphoma (AITL) patients who were treated with dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin (DA-EPOCH) regimens.
Materials and Methods
Sixty newly-diagnosed AITL patients were retrospectively enrolled in the present study. All patients were treated with DA-EPOCH regimen.
Results
Twenty-two subjects (36.7%) had a EBV DNA-positive test at diagnosis. EBV DNA‒positive patients were associated with lower lymphocyte-monocyte ratio (p=0.024). Median follow-up was 40 months (range, 14 to 100 months). The overall response rate for all the 60 AITL patents were 71.7% (95% confidence interval [CI], 58.6 to 82.5) with 3-year progressive-free survival (PFS) rate of 30.9%±6.1% and overall survival (OS) rate of 60.1%±6.6%. Not only did PFS estimation differ between the EBV DNA‒positive and EBV DNA‒negative group (hazard ratio [HR], 2.24; 95% CI, 1.15 to 4.35; p=0.006), but also worse OS was observed in the pretreatment EBV DNA‒positive group than in the EBV DNA‒negative group (HR, 2.74; 95% CI, 1.22 to 6.19; p=0.006). EBV DNA test positivity was independent prognostic marker for both PFS (HR, 2.17; 95% CI, 1.17 to 4.00; p=0.014) and OS (HR, 3.24; 95% CI, 1.48 to 7.11; p=0.004) after adjusting International Prognostic Index and prognostic index for AITL score. Reduction in EBV copies was significantly associated with therapy-response.
Conclusion
Circulating EBV DNA level was an important prognostic and monitoring marker for AITL patients who treated with DA-EPOCH regimens which cannot improve outcomes for AITL patients.

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Cutaneous peri‐ocular involvement in angioimmunoblastic T‐cell lymphoma
M. Mathieu, M. de Vicq de Cumptich, A. Kul, B. Richert
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Impact of the peripheral blood inflammatory indices and modified nomogram-revised risk index on survival of Extranodal Nasal-Type Natural Killer/T-Cell lymphoma
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Jing Zhang, Shuchao Qin, Ze Jin, Qingqing Chen, Lingxiao Xing, Tonglu Qiu, Yi Xia, Jinhua Liang, Huayuan Zhu, Li Wang, Lei Fan, Wei Xu, Jianyong Li, Yi Miao
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Dynamic changes in circulating EBV-DNA load during treatment have prognostic values in EBV+ DLBCL-NOS: a Chinese cohort study
Tong-Yao Xing, Zi-Wen Duan, Wei-Ting Wang, Kai-Xin Du, Hao-Rui Shen, Hua Yin, Jia-Zhu Wu, Yue Li, Li Wang, Jian-Yong Li, Jin-Hua Liang, Wei Xu
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Impact of Epstein-Barr Virus on Peripheral T-Cell Lymphoma Not Otherwise Specified and Angioimmunoblastic T-Cell Lymphoma
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Zheng Cao, Linshu Zeng, Lin Feng, Xiaoli Feng
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Pretreatment whole blood Epstein-Barr virus DNA predicts prognosis in Hodgkin lymphoma
Jia-Qi Qin, Hua Yin, Jia-Zhu Wu, Rui-Ze Chen, Yi Xia, Li Wang, Hua-Yuan Zhu, Lei Fan, Jian-Yong Li, Jin-Hua Liang, Wei Xu
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Davide Facchinelli, Alice Parisi, Mauro Krampera, Dino Veneri
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Cutaneous angioimmunoblastic T-cell lymphoma: Epstein-Barr virus positivity and its effects on clinicopathologic features
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Cancer Cell International.2019;[Epub] CrossRef

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Comparison of Native Escherichia coli L-Asparaginase versus Pegylated Asparaginase, in Combination with Ifosfamide, Methotrexate, Etoposide, and Prednisolone, in Extranodal NK/T-Cell Lymphoma, Nasal Type: Hyun Jee Kim, Chan-Young Ock, Tae Min Kim, Sung Hee Lee, Ju-Yeun Lee, Sun hoi Jung, Yoon Sook Cho, Miso Kim, Bhumsuk Keam, Dong-Wan Kim, Il Han Kim, Dae Seog Heo; Cancer Res Treat. 2018;50(3):670-680. Published online July 3, 2017; DOI: https://doi.org/10.4143/crt.2017.051

Abstract PDF Supplementary Material PubReader ePub

Purpose
The aim of this study was to compare asparaginase-related toxicities in two asparaginase preparations, namely native Escherichia coli L-asparaginase (L-ASP) and pegylated asparaginase (PEG-ASP) in combination with ifosfamide, methotrexate, etoposide, and prednisolone (IMEP) in natural killer (NK)/T-cell lymphoma (NTCL).
Materials and Methods
A total of 41 NTCL patients who received IMEP plus native E. coli L-ASP or PEG-ASP at Seoul National University Hospital were included in this study between January 2013 and March 2016. IMEP/ASP treatment consisted of ifosfamide, methotrexate, etoposide, plus native E. coli L-ASP (6,000 IU/m² on days 1, 3, 5, 7, 9, and 11) or PEG-ASP (2,500 IU/m² on day 1) every 3 weeks. ASP-related toxicities, toxicity patterns, length of hospital stay, and clinical outcomes were compared between the different treatment groups.
Results
The frequency of ASP-related toxicities was similar between the IMEP plus native E. coli L-ASP group and the PEG-ASP group apart from hypofibrinogenemia (native E. coli L-ASP vs. PEG-ASP group, 86.4% vs. 36.8%; p=0.001). Although post-treatment transaminase and albumin levels were significantly high and low, respectively, hepatotoxicity gradients before and after treatment did not differ significantly between the groups. Since PEG-ASP was given at an outpatient clinic in some patients, length of hospital stay was significantly shorter in the IMEP plus PEG-ASP group (median, 4.0 vs. 6.0 days; p=0.002). A favorable tendency of clinical outcomes was observed in NTCL patients treated with IMEP plus PEG-ASP (complete remission rate, 73.7% vs. 45.5%; p=0.067).
Conclusion
IMEP plus PEG-ASP showed similar ASP-related toxicities, shorter length of hospital stay, and a trend towards improved clinical outcomes compared with IMEP plus native E. coli L-ASP in NTCL.

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BMC Cancer.2018;[Epub] CrossRef

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Case Reports

Long-Term Survival after T-cell Lymphoblastic Lymphoma Treated with One Cycle of Hyper-CVAD Regimen: Il Hwan Ryu, In Sung Cho, Ah Jeong Ryu, Min Gyu Kim, Jae Woong Jeon, Joo Seok Kim, Jae Joon Lee, Ji Wook Choi, Dong Wook Kang; Cancer Res Treat. 2015;47(1):115-119. Published online August 25, 2014; DOI: https://doi.org/10.4143/crt.2013.122

Abstract PDF PubReader ePub

T-lymphoblastic lymphoma (T-LBL) is a rare form of aggressive non-Hodgkin’s lymphoma. The standard approach for management of T-LBL involves intensive multiagent chemotherapy regimens for induction and consolidation phases with central nervous system prophylaxis and a maintenance phase lasting 12-18 months. We report on a case of long-term survival after one cycle of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (hyper-CVAD) and high-dose methotrexate. A 30-year-old woman diagnosed with T-LBL with a large mediastinal mass underwent one cycle of hyper-CVAD. Four days after the start of treatment, the mediastinal mass was markedly reduced. Treatment continued with one cycle of consolidation chemotherapy, comprising high-dose methotrexate and high-dose cytarabine. The patient then refused all further chemotherapeutic treatment. Seven years have passed without relapse.

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Mayur Devraj, Chaitanya Kappagantu, Sushma Dugad, Ravidra Shinde, Komal Shah
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Paulina Stefaniuk, Agnieszka Szymczyk, Monika Podhorecka
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Lucy Sun, Alan H. Friedman, Rand Rodgers, Matthew Schear, Giovanni Greaves, Kathryn B. Freidl
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Hasan Jalaeikhoo, Mohsen Rajaeinejad, Manoutchehr Keyhani, Mohammad Zokaasadi, Mohammad Mehdi Dehghani Firoozabadi
Cancer Medicine.2018; 7(3): 594. CrossRef

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A Case of Pure Red Cell Aplasia Associated with Angioimmunoblastic T-cell Lymphoma: Jung-Hye Choi, Young-Ha Oh, Ile-Kyu Park; Cancer Res Treat. 2010;42(2):115-117. Published online June 30, 2010; DOI: https://doi.org/10.4143/crt.2010.42.2.115

Abstract PDF PubReader ePub

Pure red cell aplasia is a bone marrow failure characterized by a progressive normocytic anemia and reticulocytopenia without leucopenia and thrombocytopenia. It is associated with various hematologic diseases. However, pure red cell aplasia with angioimmunoblastic T cell lymphoma has rarely been reported. Here we describe a 43-year-old woman with pure red cell aplasia associated with angioimmunoblastic T-cell lymphoma. She had severe anemia (hemoglobin 6.9 g/dL) and a low reticulocyte count (0.2%). Direct and indirect Coombs' tests were positive. A CT scan of the abdomen revealed marked hepatosplenomegaly and small multiple lymphadenopathies. A bone marrow biopsy revealed focal infiltration of abnormal lymphoid cells and absence of red cell precursors. Splenic biopsy was compatible with angioimmunoblastic T-cell lymphoma. Ultimately, diagnosis of pure red cell aplasia associated with angioimmunoblastic T-cell lymphoma was made. After initiating CHOP therapy, the patient achieved complete remission, which was accompanied, shortly thereafter, by a rise in hemoglobin levels which finally returned to normal.

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Futoshi Iioka, Takashi Akasaka, Masahiko Hayashida, Atsuko Okumura, Hitoshi Ohno
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A Case of a Young Woman with Hepatosplenic gamadelta T-cell Lymphoma: Il Gwon Park, Cheol Won Suh, Joo Ryung Hur, Sun Jong Kim, Keon Uk Park, Seong Je Park, Don Dae Seo, Man Su Ahn, Geun Doo Jang, Woo Kun Kim; Cancer Res Treat. 2001;33(3):264-268. Published online June 30, 2001; DOI: https://doi.org/10.4143/crt.2001.33.3.264

Abstract PDF

Most T-cell lymphomas arise from mature alpabeta T-cells and commonly involve the nodes. Lymphomas bearing the gamadelta T-cell receptor (TCR) are very rare, and involve the lymph nodes minimally, if at all. Hepatosplenic gamadelta T-cell lymphoma is a recently identified, rare entity in which lymphoma cells bearing the gamadelta TCR infiltrate the sinusoids of the liver, splenic red pulp, and bone marrow. Its leukemic transformation is even more rare. Recently, we experienced a case of hepatosplenic gamadelta T-cell lymphoma in a 19-year-old woman who presented with epigastric pain, fever, massive splenomegaly, andpancytopenia. The splenectomy specimen and excisional biopsy of the liver revealed the infiltration of atypical T lymphocytes with the immunophenotypic markers of CD3 (+), CD45RO (pan-T antigen) (+), TIA-1(+), CD4(-),CD8 (-), CD56 (-), and S100 (-) in the sinusoids of the liver and splenic red pulp. Polymerase chain reaction (PCR) showed that these cells had the expression of the TCR gama gene rearrangements. Though the pancytopenia had improved after the splenectomy, the response of chemotherapy was transient. Her disease progressed rapidly and she expired in the leukemic phase. We report a case of hepatosplenic gamadelta T-cell lymphoma that developed in a young woman, along with a brief review of the literature.

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Hepatosplenic T cell lymphoma: a unifying entity in a patient with hemolytic anemia, massive splenomegaly, and liver dysfunction
Marianna Mavilia, Agnes McAuliffe, Safina Hafeez, Haleh Vaziri
Clinical Journal of Gastroenterology.2018; 11(5): 364. CrossRef
A Case of Hepatosplenic T-cell Lymphoma Diagnosed by Bone Marrow Examination
Hee Jin So, Jin Kyung Lee, Young Jun Hong, Seok-Il Hong, Hye Jin Kang, Seung-Sook Lee, Yoon Hwan Chang
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A Case of Hepatosplenic T-cell Lymphoma with Colonic Involvement
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Original Articles

Peripheral T - cell Lymphomas Presenting as Fever of Unknown Origin: Dae Seog Heo, Keun Seok Lee, Joor Yung Huh, Yung Jue Bang, Seon Yang Park, Chul Woo Kim, Byoung Kook Kim, Noe Kyeong Kim; J Korean Cancer Assoc. 1998;30(2):329-337.

Abstract PDF: PURPOSE
Peripheral T-cell lymphomas(PTCL) show diverse clinical and histological characteristics and should be understood as mixtures of heterogeneous entities. Although many clinical and biological parameters have been proposed for classifying PTCL into different prognostic groups, few parameters have turned out to be appropriate for classification. To investigate the clinical significance of FUO presentation in PTCL, comparisons of clinical parameters were performed using non-FUO presentation as a control.
MATERIALS AND METHODS
66 cases of Korean PTCL were divided into FUO group and non-FUO group according to the presentation and compared with each other.
RESULTS
Among 66 patients of PTCL, 19 patients presented with FUO. Compared with non-FUO group, FUO group showed no significant age and sex ratio differences. FUO group showed more advanced stage, worse performance status than non-FUO group. Predominant sites of definite diagnosis were skin, gastrointestinal tract and liver in FUO group and nasal cavity and paranasal sinus in non-FUO group. There were no significant differences between histologic classifications of both groups. Survival analysis revealed significant differences between both groups. FUO group showed significantly shorter survival. Prognostic factor analysis(multivariate) was done with stage, LDH level, performance status, and FUO status. FUO status, stage and performance status were significant determinants of survival, but LDH level proved to have no prognostic implication.
CONCLUSION
PTCL with FUO presentation showed such distinct characteristics that the authors propose fever of unknown origin(FUO) as a clinical parameter for classifying PTCL. Further studies are needed to identify biological parameters which characterize PTCL with FUO presentation.

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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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T - cell Receptor Gene Rearrangement in Human T - cell Lymphoid Malignancies: Seong Hoe Park, Hyung Geun Song, Chul Woo Kim, Je Geun Chi, Sang Kook Lee, Kyu Won Kim, Myoung Hee Park, Yung Jue Bang, Noe Kyeong Kim; J Korean Cancer Assoc. 1989;21(2):233-241.

Abstract PDF: We describe here the use of the southern blot hybridization technique to diagnose T-cell lymphoid malignancies by detecting clonal T-cell receptor gene rearrangements. DNA was isolated from human T-cell leukemia cell lines, peripheral blood or bone marrow cells of various leukemia patients and lymph nodes of malignant lymphoma patients, and analyzed for the presence of rearranged T-cell receptor genes, using radiolabeled T-cell recptor cDNA as probes. Among the specimen examined, clonal T-cell receptor gene rearrangements were found only in human T-cell leukemia cell lines and leukemic cells from T-cell acute lymphoblastic leukemia patients, not in non T-cell tumor cell ines, B cell lymphomas, and other types of leukemic cells from leukmia patients. These cells were checked with panels of monoclonal antibodies detecting T-cell, B-cell and other types of hematopoietic cells. Our studies indicate that detection of T-cell receptor gene rearrangement is a valuable methad for T-cell lineage specificity and clonal T-cell proliferation.

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Incidence Estimation of Primary Liver Cancer among Koreans@: Yoon Ok Ahn, Byung Joo Park, Byung Joo Park, Hyo Suk Lee, Chung Yong Kim, Takao Shigematsu; J Korean Cancer Assoc. 1989;21(2):241-249.

Abstract PDF: Medical records of the inpatients with diagnosis of either ICD-9 155, or 197, or 211 in the claims sent by medical care institutions to the Korea Medical Insurance Corporation(KMIC) during the period from January I, 1986 to December 31, 1987 were abstracted in order to identify and confirm the new cases of primary liver cancer (PLCA) among the beneficiaries of the KMIC. Using these data from the KMIC, the incidence of PLCA among Koreans was estimated as of July I, 1986 June 30, 1987. The crude rates are estimated to be 20 7 and 6.2 per 100,000 in male and female, respectively. And the cumulative rates for the age spans (I-64 and 0-74 in male are 2 55% and 3. 56%;, respectively. In female they are 0.53% and 0.91%. The adjusted rates for the world population are 30.5 in male and 7.6 in female, which are very similar to those of Osaka in Japan and of Shanghai in China. However, the truncated rates for the age group of 35-64 years old are 74. 8 in male and 15. 6 in female, which may be the highest in the world. Among Koreans in Korea increased risk of PLCA in the middle age is the notable finding. Etiologic implication of environmental exogenous factors on PLCA and need for further etiologic studies are mentioned.

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Studies on Antitumor Constituents of Stropharia rugosoannulata: Byong Kak Kim, Uhna Sung, Eung Chil Choi; J Korean Cancer Assoc. 1989;21(2):249-262.

Abstract PDF: To find physiologically active components of Korean higher fungi, high molecular weight fractions of the water extract of the cultured mycelia of Stropharia rugosoannulata were subjected to antitumor test against sarcoma 180 cells implanted in ICR mice. The partially purified fraction, Fraction A, was further purified by DEAE Sephadex A-25 column chromatography and Sephadex G-200 gel filtration chromatography. Fraction A inhibited the tumor growth at the ratio af 56.80% at a dose of 20 mg/ kg/day. It contained 22.73% polysaccharide and 30.30g protein. The polysaccharide moiety consisted of glucose, mannose, galactose, xylose and fucose. The protein moiety contained 17 amino acids, including aspartic and glutamic acids. When Fraction A was examined for immunological activity to elucidate mechanisms of its antitumor activity, it increased peritoneal exudate cells including macrophages, lymphocytes and polymorphonuclear leucocytes after 24 hours. It increased the number of hemolytic plaque-forming cells 22 times to that of the control group.

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Effect of Extracellular Protein Concentration on the In Vitro Cellular Uptake and Cytotoxicity of Etoposide ( VP - 16 ) and Teniposide ( VM - 26 ): Kyung E. Choi; J Korean Cancer Assoc. 1989;21(2):262-269.

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CD34+ Selected Peripheral Blood Stem Cell Transplantation: Hoon Kook, Hyeoung Joon Kim, Jin Soo Hwang, Keun Mo Kim, Keun Mo Kim, Ik Joo Chung, Tai Ju Hwang; J Korean Cancer Assoc. 1996;28(5):910-921.

Abstract PDF: The CD34 antigen is a 115 kDa glycoprotein that marks 1%-4% of human bone marrow cells, including virtually all committed progenitor cells and long-term reconstituting stem cells. The selection of CD34+ cells may be useful in several areas of clinical stem cell transplantation, including purging of tumor cells, T cell depletion, stem cell expansion and gene therapy. Using immunomagnetic beads method (Isolex-50TM), we report hereby the first two Korean experiences of CD34+ selected peripheral blood stem cell (PBSC) transplantations. As a mean of tumor cell purging, CD34+ cells were positively selected from mobilized PBPCs and infused to a 5-year-old girl with a relapsed stage IV neuroblastoma with resultant early short-term trilineage hematopoietic recovery. In the second patient with chronic myelogenous leukemia who showed poor graft function after having underwent an initial partially-matched bone marrow transplant, CD34+ selected allogeneic PBSC transplantation was attempted to reduce the likelihood of inducing graft-versus-host disease. Augmentation of marrow function was noted with infused PBSCs which were depleted of T cells to the degree of log3.65. As CD34+ selected PBSCs are capable of restoring hematopoietic recovery after high dose therapy, further development of selection technique to ensure high purging efficiency without significant loss of stem cells and further identification of best mobilizing and conditioning regimens are required in this new field of clinical transplantation.

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