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Case Report
Detection of HIV RNA after CAR-T Cell Therapy in A Relapsed/refractory Diffuse Large B-cell Lymphoma Patient: Possibility of False Positivity and Clinical Implications
Sang Eun Yoon, Kyungmin Huh, Tae Yeul Kim, Hee Jae Huh, Seok Jin Kim, Won Seog Kim
Received May 8, 2025  Accepted June 26, 2025  Published online June 30, 2025  
DOI: https://doi.org/10.4143/crt.2025.491    [Accepted]
AbstractAbstract PDF
CAR-T cell therapy using lentiviral vectors can lead to false-positive HIV RNA detection, making distinguishing true infection from vector-related signals challenging. A 64-year-old male with relapsed/refractory DLBCL (RR-DLBCL) underwent multiple lines of treatment, including R-CHOP, R-ICE, autologous stem cell transplantation (ASCT), and tisagenlecleucel (tisa-cel, Kymriah). Infectious disease screening before CAR-T therapy was negative for HIV. However, four months post-infusion, during evaluation for second-line CAR-T therapy targeted CD20, HIV RNA was detected in Roche Cobas HIV-1 assay targeted dual target, 5'LTR and gag gene (48 copies/mL). Serial testing showed persistent but low-level positivity of HIV RNA. Retrospective analysis of stored serum samples revealed HIV RNA negativity before tisa-cel infusion but positivity post-infusion in Roche Cobas HIV-1 assay. Additional testing using the Alinity m HIV-1 assay (dual target: 5'LTR and pol gene) and the Abbott RealTime HIV-1 assay (single-target: pol gene) confirmed that only the dual-target assay yielded positive results, suggesting lentiviral vector cross-reactivity rather than actual HIV infection. This case underscores the potential for false-positive HIV-1 RNA detection in CAR-T cell treatment recipients due to vector-derived sequences, emphasizing the need for cautious interpretation of HIV-1 testing.
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Original Article
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
AbstractAbstract PDFSupplementary MaterialPubReaderePub
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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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
AbstractAbstract PDFPubReaderePub
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.

Citations

Citations to this article as recorded by  
  • 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

    Reactions Weekly.2024; 2003(1): 302.     CrossRef
  • A systematic review of primary central nervous system lymphoma
    Lei Zhang, Qingyuan Zhang
    Holistic Integrative Oncology.2024;[Epub]     CrossRef
  • 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
    Pharmacological Research.2024; 210: 107531.     CrossRef
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Original Articles
Hematologic malignancy
Intensified First Cycle of Rituximab Plus Eight Cycles of Cyclophosphamide, Doxorubicin, Vincristine, and Prednisolone with Rituximab Chemotherapy for Advanced-Stage or Bulky Diffuse Large B-Cell Lymphoma: A Multicenter Phase II Consortium for Improving Survival of Lymphoma (CISL) Study
Yu Ri Kim, Jin Seok Kim, Won Seog Kim, Hyeon Seok Eom, Deok-Hwan Yang, Sung Hwa Bae, Hyo Jung Kim, Jae Hoon Lee, Suk-Joong Oh, Sung-Soo Yoon, Jae-Yong Kwak, Chul Won Choi, Min Kyoung Kim, Sung Young Oh, Hye Jin Kang, Seung Hyun Nam, Hyeok Shim, Joon Seong Park, Yeung-Chul Mun, Cheolwon Suh, the Korean Society of Hematology Lymphoma Working Party
Cancer Res Treat. 2023;55(4):1355-1362.   Published online March 30, 2023
DOI: https://doi.org/10.4143/crt.2023.271
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
This phase II, open-label, multicenter study aimed to investigate the efficacy and safety of a rituximab intensification for the 1st cycle with every 21-day of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP-21) among patients with previously untreated advanced-stage or bulky diffuse large B-cell lymphoma (DLBCL).
Materials and Methods
Ninety-two patients with stage III/IV or bulky DLBCL from 21 institutions were administered 8 cycles of R-CHOP-21 with an additional one dose of rituximab intensification on day 0 of the 1st cycle (RR-CHOP). The primary endpoint was a complete response (CR) rate after 3 cycles of chemotherapy.
Results
Among the 92 DLBCL patients assessed herein, the response rate after 3 cycles of chemotherapy was 88.0% (38.0% CR+50.0% partial response [PR]). After the completion of 8 cycles of chemotherapy, the overall response rate was observed for 68.4% (58.7% CR+9.8% PR). The 3-year progression-free survival rate was 64.0%, and the 3-year overall survival rate was 70.4%. Febrile neutropenia was one of the most frequent grade 3 adverse events (40.0%) and 5 treatment-related deaths occurred. Compared with the clinical outcomes of patients who received R-CHOP chemotherapy as a historical control, the interim CR rate was higher in male patients with RR-CHOP (20.5% vs. 48.8%, p=0.016).
Conclusion
Rituximab intensification on days 0 to the 1st cycle of the standard 8 cycles R-CHOP-21 for advanced DLBCL yielded favorable response rates after the 3 cycles of chemotherapy and acceptable toxicities, especially for male patients. ClinicalTrials.gov ID: NCT01054781.
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Outcomes in Refractory Diffuse Large B-Cell Lymphoma: Results from Two Prospective Korean Cohorts
Jun Ho Yi, Seong Hyun Jeong, Seok Jin Kim, Dok Hyun Yoon, Hye Jin Kang, Youngil Koh, Jin Seok Kim, Won-Sik Lee, Deok-Hwan Yang, Young Rok Do, Min Kyoung Kim, Kwai Han Yoo, Yoon Seok Choi, Whan Jung Yun, Yong Park, Jae-Cheol Jo, Hyeon-Seok Eom, Jae-Yong Kwak, Ho-Jin Shin, Byeong Bae Park, Seong Yoon Yi, Ji-Hyun Kwon, Sung Yong Oh, Hyo Jung Kim, Byeong Seok Sohn, Jong Ho Won, Dae-Sik Hong, Ho-Sup Lee, Gyeong-Won Lee, Cheolwon Suh, Won Seog Kim
Cancer Res Treat. 2023;55(1):325-333.   Published online April 22, 2022
DOI: https://doi.org/10.4143/crt.2022.008
AbstractAbstract PDFPubReaderePub
Purpose
Diffuse large B-cell lymphoma (DLBCL) is the most common hematologic malignancy worldwide. Although substantial improvement has been achieved by the frontline rituximab-based chemoimmunotherapy, up to 40%-50% of patients will eventually have relapsed or refractory disease, whose prognosis is extremely dismal.
Materials and Methods
We have carried out two prospective cohort studies that include over 1,500 DLBCL patients treated with rituximab plus CHOP (#NCT01202448 and #NCT02474550). In the current report, we describe the outcomes of refractory DLBCL patients. Patients were defined to have refractory DLBCL if they met one of the followings, not achieving at least partial response after 4 or more cycles of R-CHOP; not achieving at least partial response after 2 or more cycles of salvage therapy; progressive disease within 12 months after autologous stem cell transplantation.
Results
Among 1,581 patients, a total of 260 patients met the criteria for the refractory disease after a median time to progression of 9.1 months. The objective response rate of salvage treatment was 26.4%, and the complete response rate was 9.6%. The median overall survival (OS) was 7.5 months (95% confidence interval, 6.4 to 8.6), and the 2-year survival rate was 22.1%±2.8%. The median OS for each refractory category was not significantly different (p=0.529).
Conclusion
In line with the previous studies, the outcomes of refractory DLBCL patients were extremely poor, which necessitates novel approaches for this population.

Citations

Citations to this article as recorded by  
  • PI3Kδ inhibitor linperlisib combined with gemcitabine and oxaliplatin for relapsed or refractory diffuse large B-cell lymphoma: a multicenter, single-arm phase Ib/II trial
    Peng Sun, Hong Cen, Haiyan Yang, Rui Huang, Zhen Cai, Xuekui Gu, Hanying Bao, Zusheng Xu, Zuhong Xu, Zhi-Ming Li
    Cancer Cell International.2025;[Epub]     CrossRef
  • Improving access to chimeric antigen receptor T-cells for refractory or relapsing diffuse large B cell lymphoma therapy in Asia
    Ya Hwee Tan, Dok Hyun Yoon, Andrew J. Davies, Christian Buske, Yang Liang Boo, Nagavalli Somasundaram, Francesca Lim, Shin Yeu Ong, Anand Jeyasekharan, Koji Izutsu, Won Seog Kim, Jason Yongsheng Chan
    Discover Oncology.2025;[Epub]     CrossRef
  • Recent advances in cellular immunotherapy for lymphoid malignancies
    Haerim Chung, Hyunsoo Cho
    Blood Research.2023; 58(4): 166.     CrossRef
  • Sphingosine 1-phosphate receptor, a new therapeutic direction in different diseases
    Hongyu Chen, Junmin Wang, Caiyun Zhang, Peilun Ding, Shuxia Tian, Junming Chen, Guang Ji, Tao Wu
    Biomedicine & Pharmacotherapy.2022; 153: 113341.     CrossRef
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Predictive Parameters of Febrile Neutropenia and Clinical Significance of G-CSF Receptor Signaling Pathway in the Development of Neutropenia during R-CHOP Chemotherapy with Prophylactic Pegfilgrastim in Patients with Diffuse Large B-Cell Lymphoma
Do Young Kim, Jehyun Nam, Joo-Seop Chung, Byeol Eun Jeon, Ji Hyun Lee, Jae-Cheol Jo, Sang-Woo Kim, Ho-Jin Shin
Cancer Res Treat. 2022;54(4):1256-1267.   Published online December 31, 2021
DOI: https://doi.org/10.4143/crt.2021.944
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Pegfilgrastim is widely used to prevent chemotherapy-induced neutropenia (CIN) and febrile neutropenia (FN) in patients with diffuse large B-cell lymphoma (DLBCL). We investigated the predictive factors affecting CIN and FN incidence in patients with DLBCL receiving rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy with pegfilgrastim and conducted experiments to find reason for the occurrence of CIN even when pegfilgrastim was used.
Materials and Methods
We reviewed the CIN and FN events of 200 patients with DLBCL. Based on these data, we investigate the association with predictive factor and the levels of granulocyte-colony stimulating factor (G-CSF) receptor signaling pathway markers (pSTAT3, pAKT, pERK1/2, pBAD, and CXCR4) in bone marrow (BM) samples isolated from patients with DLBCL.
Results
FN was significantly associated with stage III/IV (hazard ratio [HR], 12.74) and low serum albumin levels (HR, 3.87). Additionally, patients with FN had lower progression-free survival (PFS; 2-year PFS, 51.1 % vs. 74.0%) and overall survival (OS; 2-year OS, 58.2% vs. 85.0%) compared to those without FN. The occurrence of CIN was associated with overexpression of G-CSF receptor signaling pathway markers, and expression levels of these markers were upregulated in BM cells co-cultured with DLBCL cells. The rate of neutrophil apoptosis was also higher in neutrophils co-cultured with DLBCL cells and was further promoted by treatment with doxorubicin.
Conclusion
Our findings suggest that high DLBCL burden may alter the BM environment and G-CSF receptor signaling pathway, even in chemotherapy-naïve state, which may increase CIN frequency during R-CHOP chemotherapy.

Citations

Citations to this article as recorded by  
  • Hypogammaglobulinemia at Diagnosis is Associated With Inferior Survival and Higher Risk of Infections in Diffuse Large B Cell Lymphoma
    Åsa Lindberg, Åsa Johansson, Fredrik Kahn, Göran Jönsson, Mats Jerkeman
    Hematological Oncology.2025;[Epub]     CrossRef
  • Predictive Model for Occurrence of Febrile Neutropenia after Chemotherapy in Patients with Diffuse Large B-Cell Lymphoma: A Multicenter, Retrospective, Observational Study
    Masaya Morimoto, Yuma Yokoya, Kikuaki Yoshida, Hideki Kosako, Yoshikazu Hori, Toshiki Mushino, Shinobu Tamura, Reiko Ito, Ryosuke Koyamada, Takuya Yamashita, Shinichiro Mori, Nobuyoshi Mori, Sachiko Ohde
    Hematology Reports.2024; 16(1): 76.     CrossRef
  • Multi‐omics integration reveals the oncogenic role of eccDNAs in diffuse large B‐cell lymphoma through STING signalling
    Zijuan Wu, Wei Zhang, Luqiao Wang, Jiayan Leng, Yongle Li, Zhou Fan, Mengtao Zhan, Lei Cao, Yongning Jiang, Yan Jiang, Bing Sun, Jianxin Fu, Jianyong Li, Wenyu Shi, Hui Jin
    Clinical and Translational Medicine.2024;[Epub]     CrossRef
  • Transcriptomic analysis of neutrophil apoptosis induced by diffuse large B-cell lymphoma unveils a potential role in neutropenia
    Byeol-Eun Jeon, Ji-Eun Lee, Jungwook Park, Hyejung Jung, Eun Gyung Park, Du Hyeong Lee, Young-Su Seo, Heui-Soo Kim, Ho-Jin Shin, Sang-Woo Kim
    Genes & Genomics.2023; 45(8): 1013.     CrossRef
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Pegfilgrastim Prophylaxis Is Effective in the Prevention of Febrile Neutropenia and Reduces Mortality in Patients Aged ≥ 75 Years with Diffuse Large B-Cell Lymphoma Treated with R-CHOP: A Prospective Cohort Study
Seong Hyun Jeong, Seok Jin Kim, Dok Hyun Yoon, Yong Park, Hye Jin Kang, Youngil Koh, Gyeong-Won Lee, Won-Sik Lee, Deok-Hwan Yang, Young Rok Do, Min Kyoung Kim, Kwai Han Yoo, Yoon Seok Choi, Hwan Jung Yun, Jun Ho Yi, Jae-Cheol Jo, Hyeon-Seok Eom, Jae-Yong Kwak, Ho-Jin Shin, Byeong Bae Park, Shin Young Hyun, Seong Yoon Yi, Ji-Hyun Kwon, Sung Yong Oh, Hyo Jung Kim, Byeong Seok Sohn, Jong Ho Won, Se-Hyung Kim, Ho-Sup Lee, Cheolwon Suh, Won Seog Kim
Cancer Res Treat. 2022;54(4):1268-1277.   Published online December 30, 2021
DOI: https://doi.org/10.4143/crt.2021.1168
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Febrile neutropenia (FN) can cause suboptimal treatment and treatment-related mortality (TRM) in diffuse large B-cell lymphoma (DLBCL) patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP).
Materials and methods
We conducted a prospective cohort study to evaluate the effectiveness of pegfilgrastim prophylaxis in DLBCL patients receiving R-CHOP, and we compared them with the PROCESS cohort (n=485).
Results
Since January 2015, 986 patients with DLBCL were enrolled. Pegfilgrastim was administered at least once in 930 patients (94.3%), covering 90.3% of all cycles. FN developed in 137 patients (13.9%) in this cohort (23.7% in the PROCESS cohort, p<0.001), and 4.2% of all cycles (10.2% in the PROCESS cohort, p<0.001). Dose delay was less common (≥3 days: 18.1% vs. 23.7%, p=0.015; ≥5 days: 12.0% vs. 18.3%, p=0.023) in this cohort than in the PROCESS cohort. The incidence of TRM (3.2% vs. 5.6%, p=0.047) and infection-related death (1.8% vs. 4.5%, p=0.004) was lower in this cohort than in the PROCESS cohort. The 4-year overall survival (OS) and progression-free survival (PFS) rates of the two cohorts were not different (OS: 73.0% vs. 71.9%, p=0.545; PFS: 69.5% vs. 68.8%, p=0.616). However, in patients aged ≥75 years, the 4-year OS and PFS rates were higher in this cohort than in the PROCESS cohort (OS: 49.6% vs. 33.7%, p=0.032; PFS: 44.2% vs. 30.3% p=0.047).
Conclusion
Pegfilgrastim prophylaxis is effective in the prevention of FN and infection-related death in DLBCL patients receiving R-CHOP, and it also improves OS in patients aged ≥75 years.

Citations

Citations to this article as recorded by  
  • Sarcopenia attenuates the efficacy of PEGylated granulocyte colony-stimulating factor in preventing febrile neutropenia
    Se-Il Go, Eun-Jeong Jeong, Woo Je Lee, Sungwoo Park, Mi Jung Park, Gyeong-Won Lee
    Supportive Care in Cancer.2025;[Epub]     CrossRef
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  • 305 Download
  • 2 Web of Science
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Lymphoma
Prognostic Impact of Age at the Time of Diagnosis in Korean Patients with Diffuse Large B-cell Lymphoma in the Rituximab Era: A Single Institution Study
Hee Sang Hwang, Meejeong Kim, Chan-Sik Park, Dok Hyun Yoon, Cheolwon Suh, Jooryung Huh, Heounjeong Go
Cancer Res Treat. 2021;53(1):270-278.   Published online September 15, 2020
DOI: https://doi.org/10.4143/crt.2020.626
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
In contrast to the Western diffuse large B-cell lymphoma (DLBCL), prognostic impact of age in a Korean population with DLBCL has not been fully evaluated.
Materials and Methods
Six hundred and eight DLBCL patients treated with rituximab-containing chemotherapeutic regimens from January 2002 to March 2012 in Asan Medical Center were enrolled. Survival models using the restricted cubic spine−transformed age variable were constructed to evaluate non-linear relationships between age and survival outcome. Finally, age was categorized according to the conventional international prognostic index (IPI), National Comprehensive Cancer Network (NCCN)-IPI, and Grupo Español de Linfomas/Trasplante Autólogo de Médula Ósea (GELTAMO)-IPI schemes and the prognostic implications were evaluated.
Results
The relative hazard did not change significantly during the first to fifth decades, but began to increase exponentially in patients aged over 62 years. This pattern or relationship was also retained in a multivariate model fitted to the age-adjusted IPI and relative dose intensity. Multivariate survival analysis revealed that age > 75 years, but not age > 60 years, was associated independently with poor overall and progression-free survival when the relative dose intensity and age-adjusted IPI were taken into account.
Conclusion
The outcome of DLBCL in Korean populations may deteriorate rapidly as age exceeds 62 years. Therefore, a consensus cutoff value for age in Korean DLBCL patients should be determined to better predict prognosis.

Citations

Citations to this article as recorded by  
  • SOHO State of the Art Updates and Next Questions | Diffuse Large B-Cell Lymphoma in Older Adults: A Comprehensive Review
    Varun Iyengar, Paul Hamlin, Pallawi Torka
    Clinical Lymphoma Myeloma and Leukemia.2025; 25(6): 395.     CrossRef
  • Two distinct age-prognosis patterns in patients with esophageal cancer undergoing surgical and radiotherapy treatments: a combined analysis of 3JECROG and SEER databases
    Chen Li, Xiao Chang, Qifeng Wang, Qingsong Pang, Zefen Xiao, Wencheng Zhang, Zhiyong Yuan
    Therapeutic Advances in Medical Oncology.2024;[Epub]     CrossRef
  • Impact of R-CHOP dose intensity on survival outcomes in diffuse large B-cell lymphoma: a systematic review
    Edward J. Bataillard, Chan Yoon Cheah, Matthew J. Maurer, Arushi Khurana, Toby A. Eyre, Tarec Christoffer El-Galaly
    Blood Advances.2021; 5(9): 2426.     CrossRef
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Case Report
Diffuse Large B-Cell Lymphoma Arising within Ileal Neobladder: An Expanding Spectrum of Diffuse Large B-Cell Lymphoma Associated with Chronic Inflammation
Hyekyung Lee, Hyunbin Shin, Nae Yu Kim, Hyun Sik Park, Jinsung Park
Cancer Res Treat. 2019;51(4):1666-1670.   Published online March 22, 2019
DOI: https://doi.org/10.4143/crt.2019.022
AbstractAbstract PDFPubReaderePub
Diffuse large B-cell lymphoma associated with chronic inflammation (DLBCL-CI), specifically arising in ileal neobladder, is a rare neoplasm. We present an unusual case of Epstein– Barr virus (EBV)–positive DLBCL-CI arising within neobladder with detailed clinical, histological, and immunophenotypical features in an immunocompetent patient. An 88-year-old male was admitted for gross hematuria. He had undergone radical cystectomy and ileal neobladder 17 years ago for invasive bladder cancer. Computed tomography showed enhancing lesions on dome and posterior wall of neobladder with mucosal thickening and multiple enlarged retroperitoneal lymphadenopathies. Transurethralresection of neobladder lesion revealed the diffuse infiltration of large lymphoid cells which were positive for CD20, CD30, and multiple myeloma oncogen-1 with EBV-encoded small RNAs co-localizing, and diagnosis of EBV-positive DLBCL-CI was made. After multi-agent chemotherapy, the lesion disappeared. We suggest that clinicians should consider the possibility of DLBCL-CI in patients presented with hematuria during follow-up after bladder reconstruction.

Citations

Citations to this article as recorded by  
  • Advances in the Pathogenesis of EBV-Associated Diffuse Large B Cell Lymphoma
    Paola Chabay
    Cancers.2021; 13(11): 2717.     CrossRef
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Original Articles
Dose-Dense Rituximab-CHOP versus Standard Rituximab-CHOP in Newly Diagnosed Chinese Patients with Diffuse Large B-Cell Lymphoma: A Randomized, Multicenter, Open-Label Phase 3 Trial
Xueying Li, He Huang, Bing Xu, Hongqiang Guo, Yingcheng Lin, Sheng Ye, Jiqun Yi, Wenyu Li, Xiangyuan Wu, Wei Wang, Hongyu Zhan, Derong Xie, Jiewen Peng, Yabing Cao, Xingxiang Pu, Chengcheng Guo, Huangming Hong, Zhao Wang, Xiaojie Fang, Yong Zhou, Suxia Lin, Qing Liu, Tongyu Lin
Cancer Res Treat. 2019;51(3):919-932.   Published online October 2, 2018
DOI: https://doi.org/10.4143/crt.2018.230
AbstractAbstract PDFPubReaderePub
Purpose
Rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone administered every 3 weeks (R-CHOP-21) is the standard care for diffuse large B-cell lymphoma (DLBCL). It is unknown whether the dose-dense R-CHOP (R-CHOP-14) could improve the outcome of the disease in Asian population.
Materials and Methods
Newly diagnosed DLBCL patients were centrally, randomly assigned (1:1) to receive R-CHOP- 14 or R-CHOP-21. R-CHOP-14 was administered every 2 weeks, and R-CHOP-21 was administered every 3 weeks. Primary end point was disease-free survival (DFS). Secondary end points included overall survival (OS), progression-free survival (PFS), response rate and toxicities.
Results
Seven hundred and two patients were randomly assigned to receive R-CHOP-14 (n=349) or R-CHOP-21 (n=353). With a median follow-up of 45.6 months, the two groups did not differ significantly in 3-year DFS (79.6% for R-CHOP-14 vs. 83.2% for R-CHOP-21, p=0.311), 3-year OS (77.5% for R-CHOP-14 vs. 77.6% for R-CHOP-21, p=0.903), or 3-year PFS (63.2% for R-CHOP-14 vs. 66.1% for R-CHOP-21, p=0.447). Patients with an International Prognostic Index (IPI) score ≥ 2 had a poorer prognosis compared to those with an IPI score < 2. Grade 3/4 hematologic and non-hematologic toxicities were manageable and similar between R-CHOP-14 and R-CHOP-21.
Conclusion
R-CHOP-14 did not improve the outcome of DLBCL compared to R-CHOP-21 in Asian population. With manageable and similar toxicities, both of the two regimens were suitable for Asian DLBCL patients. For high-risk patients with IPI ≥ 2, new combination regimens based on R-CHOP deserve further investigation to improve efficacy.

Citations

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  • Definitions and use of tumor bulk in phase 3 lymphoma trials: a comprehensive literature review
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Multicenter Retrospective Analysis of Clinical Characteristics, Treatment Patterns, and Outcomes in Very Elderly Patients with Diffuse Large B-Cell Lymphoma: The Korean Cancer Study Group LY16-01
Jung Hye Choi, Tae Min Kim, Hyo Jung Kim, Sung Ae Koh, Yeung-Chul Mun, Hye Jin Kang, Yun Hwa Jung, Hyeok Shim, So Young Chong, Der-Sheng Sun, Soonil Lee, Byeong Bae Park, Jung Hye Kwon, Seung-Hyun Nam, Jun Ho Yi, Young Jin Yuh, Jong-Youl Jin, Jae Joon Han, Seok-Hyun Kim
Cancer Res Treat. 2018;50(2):590-598.   Published online June 9, 2017
DOI: https://doi.org/10.4143/crt.2017.172
AbstractAbstract PDFPubReaderePub
Purpose
The treatment strategy for elderly patients older than 80 years with diffuse large B-cell lymphoma (DLBCL) has not been established because of poor treatment tolerability and lack of data.
Materials and Methods
This multicenter retrospective study was conducted to investigate clinical characteristics, treatment patterns and outcomes of patients older than 80 years who were diagnosed with DLBCL at 19 institutions in Korea between 2005 and 2016.
Results
A total of 194 patients were identified (median age, 83.3 years). Of these, 114 patients had an age-adjusted International Prognostic Index (aaIPI) score of 2-3 and 48 had a Charlson index score of 4 or more. R-CHOP was given in 124 cases, R-CVP in 13 cases, other chemotherapy in 17 cases, radiation alone in nine cases, and surgery alone in two cases. Twenty-nine patients did not undergo any treatment. The median number of chemotherapy cycles was three. Only 37 patients completed the planned treatment cycles. The overall response rate from 105 evaluable patientswas 90.5% (complete response, 41.9%). Twentynine patients died due to treatment-related toxicities (TRT). Thirteen patients died due to TRT after the first cycle. Median overall survival was 14.0 months. The main causes of death were disease progression (30.8%) and TRT (27.1%). In multivariate analysis, overall survival was affected by aaIPI, hypoalbuminemia, elevated creatinine, and treatment.
Conclusion
Age itself should not be a contraindication to treatment. However, since elderly patients show higher rates of TRT due to infection, careful monitoring and dose modification of chemotherapeutic agents is needed.

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Cross-sectional Study of Patients with Diffuse Large B-Cell Lymphoma: Assessing the Effect of Host Status, Tumor Burden, and Inflammatory Activity on Venous Thromboembolism
Sung Hee Lim, Sook-young Woo, Seonwoo Kim, Young Hyeh Ko, Won Seog Kim, Seok Jin Kim
Cancer Res Treat. 2016;48(1):312-321.   Published online March 2, 2015
DOI: https://doi.org/10.4143/crt.2014.266
AbstractAbstract PDFPubReaderePub
Purpose
The risk factors for venous thromboembolism (VTE) in diffuse large B-cell lymphoma (DLBCL) are not clear although thrombosis can be associated with host status, tumor burden, and inflammatory activity. We assessed the effect of those factors on VTE in a cross-sectional study of patients enrolled in a prospective cohort study. Materials and Methods We analyzed the occurrence of VTE in 322 patients with newly diagnosed DLBCL who received rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) between 2008 and 2011. Serum levels of inflammatory cytokines were measured from serum samples archived at diagnosis.
Results
With a median follow-up duration of 41.9 months, VTE was documented in 34 patients (10.6%). A comparison of baseline characteristics indicated the group with VTE had higher percentage of old age, stage III/IV and extranodal involvements than the group without VTE (p < 0.05). Thus, the International Prognostic Index was significantly associated with VTE, but the Khorana score was not. A univariate competing risk factor analysis for VTE revealed that increased levels of inflammatory cytokines such as interleukin (IL)-6 and IL-10 were also associated with VTE (p < 0.05) in addition to host and tumor burden. However, a multivariate analysis showed that two host factors including age (≥ 60 years) and poor performance were independent risk factors for VTE. Conclusion Among potential risk factors for VTE including tumor burden and inflammatory activity, age and performance status had a strong impact on the occurrence of VTE in patients with DLBCL who received R-CHOP.

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Case Report
Diffuse Large B-Cell Lymphoma with Involvement of the Breast and Testis in a Male Patient
Eunji Choi, Jae-Cheol Jo, Dok Hyun Yoon, Shin Kim, Kyoungmin Lee, Jooryung Huh, Chan-Sik Park, Sang Wook Lee, Cheolwon Suh
Cancer Res Treat. 2015;47(3):539-543.   Published online September 11, 2014
DOI: https://doi.org/10.4143/crt.2013.245
AbstractAbstract PDFPubReaderePub
Here we report a case of a 76-year-old man with diffuse large B-cell lymphoma (DLBCL) with simultaneous involvement of the right breast and left testicle. The patient underwent complete resection of the involved testis, followed by immunochemotherapy with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) and prophylactic radiotherapy to the contralateral testis. Following this multimodal therapy, he achieved a complete response. This is a rare case of DLBCL involving both the breast and the testis in a male patient.

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  • Rare incidence of diffuse large B-cell lymphoma (DLBCL) with bilateral breast and testicular involvement in a male patient: A case report and review of the literature
    Sarah Ayad, Anuraag Sah, Kirolos Gergis, Michelle Cholankeril
    Current Problems in Cancer: Case Reports.2022; 5: 100142.     CrossRef
  • Primary breast lymphoma in males: Incidence, demographics, prognostic factors, survival, and comparisons with females
    Jie Zhang, Binbin Ma, Hong Ji, Rong Guo
    Frontiers in Surgery.2022;[Epub]     CrossRef
  • Diffuse Large B-Cell Breast Lymphoma: A Case Series
    Afaf H Al Battah, Einas A Al Kuwari, Zsolt Hascsi, Abdulqadir J Nashwan, Halima Elomari, Hisham Elsabah, Safa Al Azawi, Samah Kohla, Dina Soliman, Mohamed A Yassin
    Clinical Medicine Insights: Blood Disorders.2017; 10: 1179545X1772503.     CrossRef
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Original Article
Clinical Outcome of Rituximab-Based Therapy (RCHOP) in Diffuse Large B-Cell Lymphoma Patients with Bone Marrow Involvement
Byung Woog Kang, Joon Ho Moon, Yee Soo Chae, Soo Jung Lee, Jong Gwang Kim, Yeo-Kyeoung Kim, Je-Jung Lee, Deok-Hwan Yang, Hyeoung-Joon Kim, Jin Young Kim, Young Rok Do, Keon Uk Park, Hong Suk Song, Ki Young Kwon, Min Kyung Kim, Kyung Hee Lee, Myung Soo Hyun, Hun Mo Ryoo, Sung Hwa Bae, Hwak Kim, Sang Kyun Sohn
Cancer Res Treat. 2013;45(2):112-117.   Published online June 30, 2013
DOI: https://doi.org/10.4143/crt.2013.45.2.112
AbstractAbstract PDFPubReaderePub
PURPOSE
We investigated the clinical outcome of bone marrow (BM) involvement in patients with diffuse large B-cell lymphoma (DLBCL) who received rituximab-based therapy.
MATERIALS AND METHODS
A total of 567 consecutive patients with newly diagnosed DLBCL treated with rituximab-CHOP (RCHOP) between November 2001 and March 2010 were included in the current study. All of the patients underwent a BM study at the initial staging and the clinical characteristics and prognosis of these patients with or without BM involvement were analyzed retrospectively.
RESULTS
The total cohort included 567 patients. The overall incidence of BM involvement was 8.5%. With a median follow-up duration of 33.2 months (range, 0.1 to 80.7 months) for patients who were alive at the last follow-up, the five-year overall survival (OS) and event-free survival (EFS) rate in patients without BM involvement (76.3% and 67.5%, p<0.001) was statistically higher than that in patients with BM involvement (44.3% and 40.1%, p<0.001). In multivariate analysis, among total patients, BM involvement showed a significant association with OS and EFS. In univariate and multivariate analyses, even among stage IV patients, a significant association with worse EFS was observed in the BM involvement group.
CONCLUSION
BM involvement at diagnosis affected the survival of patients with DLBCL who received RCHOP. Although use of RCHOP can result in significant improvement of the therapeutic effect of DLBCL, BM involvement is still a negative prognostic factor of DLBCL patients in the era of rituximab.

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    Haruya Okamoto, Nobuhiko Uoshima, Ayako Muramatsu, Reiko Isa, Takahiro Fujino, Yayoi Matsumura-Kimoto, Taku Tsukamoto, Shinsuke Mizutani, Yuji Shimura, Tsutomu Kobayashi, Eri Kawata, Hitoji Uchiyama, Junya Kuroda
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    PLOS ONE.2018; 13(7): e0199708.     CrossRef
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    Maria Joao Baptista, Olga Garcia, Mireia Morgades, Eva Gonzalez-Barca, Pilar Miralles, Armando Lopez-Guillermo, Eugenia Abella, Miriam Moreno, Juan-Manuel Sancho, Evarist Feliu, Josep-Maria Ribera, Jose-Tomas Navarro
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  • Non-Hodgkin Lymphomas: Impact of Rituximab on Overall Survival of Patients with Diffuse Large B-Cell and Follicular Lymphoma
    José Carlos Jaime-Pérez, Carmen Magdalena Gamboa-Alonso, Alberto Vázquez-Mellado de Larracoechea, Marisol Rodríguez-Martínez, César Homero Gutiérrez-Aguirre, Luis Javier Marfil-Rivera, David Gómez-Almaguer
    Archives of Medical Research.2015; 46(6): 454.     CrossRef
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Case Report
Unusual Presentation of Large B Cell Lymphoma- Bone and Stomach- Treated with Autologous Transplantation
Bokyung Kim, Sung Yong Oh, Suee Lee, Hyuk-Chan Kwon, Sung-Hyun Kim, Sook Hee Hong, Sung-Soo Kim, Hyo-Jin Kim
Cancer Res Treat. 2007;39(4):181-184.   Published online December 31, 2007
DOI: https://doi.org/10.4143/crt.2007.39.4.181
AbstractAbstract PDFPubReaderePub

Extranodal presentation of diffuse large B cell lymphoma (DLBL) is frequently observed in the gastrointestinal tract, CNS, bone, testes and liver. However, the simultaneous detection of multiple extranodal involvement at presentation is quite an uncommon occurrence. In this study, we report on a patient with an uncommon presentation of DLBL, and he had symptoms of left knee joint pain and hematemesis, characterized by bone and stomach involvement. Computed tomography and fluorodeoxyglucose-positron emission tomography (FDG-PET) scanning revealed a rapid, extensive spread to the bones and soft tissues. Subsequent histopathological examination verified the bony and gastric CD20-positive DLBL localization. We diagnosed this case as DLBL of stage IV with an international prognostic index of 3, and classified him into the high intermediate risk group. This patient was treated via chemotherapy with an R-CHOP regimen. After achieving a partial response, the patient received autologous peripheral blood stem cell transplantation. The patient attained partial remission, as shown on the FDG-PET scan, and he displayed improvement of his left femur pain.

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Cancer Res Treat : Cancer Research and Treatment
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