Cancer Research and Treatment

Original Articles

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; Received May 21, 2024 Accepted July 15, 2024 Published online July 16, 2024; DOI: https://doi.org/10.4143/crt.2024.479 [Epub ahead of print]

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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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; Received February 14, 2024 Accepted July 4, 2024 Published online July 5, 2024; DOI: https://doi.org/10.4143/crt.2024.155 [Epub ahead of print]

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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Pediatric cancer

Stratified Treatment in Pediatric Anaplastic Large Cell Lymphoma: Result of a Prospective Open-Label Multiple-Institution Study: Tingting Chen, Chenggong Zeng, Juan Wang, Feifei Sun, Junting Huang, Jia Zhu, Suying Lu, Ning Liao, Xiaohong Zhang, Zaisheng Chen, Xiuli Yuan, Zhen Yang, Haixia Guo, Liangchun Yang, Chuan Wen, Wenlin Zhang, Yang Li, Xuequn Luo, Zelin Wu, Lihua Yang, Riyang Liu, Mincui Zheng, Xiangling He, Xiaofei Sun, Zijun Zhen; Cancer Res Treat. 2024;56(4):1252-1261. Published online May 28, 2024; DOI: https://doi.org/10.4143/crt.2024.104

Abstract PDF Supplementary Material PubReader ePub: Purpose
The risk stratification of pediatric anaplastic large cell lymphoma (ALCL) has not been standardized. In this study, new risk factors were included to establish a new risk stratification system for ALCL, and its feasibility in clinical practice was explored.
Materials and Methods
On the basis of the non-Hodgkin’s lymphoma Berlin–Frankfurt–Munster 95 (NHL-BFM-95) protocol, patients with minimal disseminated disease (MDD), high-risk tumor site (multiple bone, skin, liver, and lung involvement), and small cell/lymphohistiocytic (SC/LH) pathological subtype were enrolled in risk stratification. Patients were treated with a modified NHL-BFM-95 protocol combined with an anaplastic lymphoma kinase inhibitor or vinblastine (VBL).
Results
A total of 136 patients were enrolled in this study. The median age was 8.8 years. The 3-year event-free survival (EFS) and overall survival of the entire cohort were 77.7% (95% confidence interval [CI], 69.0% to 83.9%) and 92.3% (95% CI, 86.1% to 95.8%), respectively. The 3-year EFS rates of low-risk group (R1), intermediate-risk group (R2), and high-risk group (R3) patients were 100%, 89.5% (95% CI, 76.5% to 95.5%), and 67.9% (95% CI, 55.4% to 77.6%), respectively. The prognosis of patients with MDD (+), stage IV cancer, SC/LH lymphoma, and high-risk sites was poor, and the 3-year EFS rates were 45.3% (95% CI, 68.6% to 19.0%), 65.7% (95% CI, 47.6% to 78.9%), 55.7% (95% CI, 26.2% to 77.5%), and 70.7% (95% CI, 48.6% to 84.6%), respectively. At the end of follow-up, one of the five patients who received maintenance therapy with VBL relapsed, and seven patients receiving anaplastic lymphoma kinase inhibitor maintenance therapy did not experience relapse.
Conclusion
This study has confirmed the poor prognostic of MDD (+), high-risk site and SC/LH, but patients with SC/LH lymphoma and MDD (+) at diagnosis still need to receive better treatment (ClinicalTrials.gov number, NCT03971305).

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Head and Neck cancer

The Impact of Infectious Mononucleosis History on the Risk of Developing Lymphoma and Nasopharyngeal Carcinoma: A Retrospective Large-Scale Cohort Study Using National Health Insurance Data in South Korea: So Hee Kang, Yun-Hee Lee, Jun-Pyo Myong, Minsu Kwon; Cancer Res Treat. 2024;56(4):1077-1083. Published online April 23, 2024; DOI: https://doi.org/10.4143/crt.2023.1356

Abstract PDF Supplementary Material PubReader ePub: Purpose
This study aimed to assess the long-term risks associated with a history of infectious mononucleosis (IM), primarily caused by the Epstein-Barr virus (EBV). Specifically analyzing the potential increase in developing nasopharyngeal cancer (NPC) and lymphoma in patients with a history of IM and exploring the prevalence of other EBV-associated conditions.
Materials and Methods
The Korean National Health Insurance Service (NHIS) database was utilized for a retrospective analysis, covering data from 2002 to 2021. A total of 25,582 IM patients and controls were included, with 1:1 propensity score matching. The study monitored outcomes, including lymphoma, NPC, gastric cancer, multiple sclerosis, and all-cause mortality.
Results
Patients with a history of IM demonstrated a significantly higher incidence of lymphoma (hazard ratio [HR], 5.320; 95% confidence interval [CI], 3.208 to 8.820; p < 0.001) and NPC (HR, 7.116; 95% CI, 1.617 to 31.314; p=0.009) during the follow-up period compared with the control group. Additionally, the IM group showed an increased rate of all-cause mortality (HR, 2.225; 95% CI, 1.858 to 2.663; p < 0.001).
Conclusion
This study suggests that individuals with a history of IM have an elevated risk of developing lymphoma and NPC in South Korea, emphasizing the importance of vigilant follow-up and monitoring. The results advocate for heightened awareness and potential national monitoring policies to address the long-term health implications of EBV infection and to implement preventive measures.

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Hematologic malignancy

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 Res Treat. 2024;56(3):920-935. Published online January 16, 2024; DOI: https://doi.org/10.4143/crt.2023.869

Abstract PDF Supplementary Material PubReader ePub

Purpose
The feasibility of sequencing circulating tumor DNA (ctDNA) in plasma as a biomarker to predict early relapse or poor prognosis in patients with follicular lymphoma (FL) receiving systemic immunochemotherapy is not clear.
Materials and Methods
We sequenced DNA from cell-free plasma that was serially obtained from newly diagnosed FL patients undergoing systemic immunochemotherapy. The mutation profiles of ctDNA at the time of diagnosis and at response evaluation and relapse and/or progression were compared with clinical course and treatment outcomes.
Results
Forty samples from patients receiving rituximab-containing immunochemotherapy were analyzed. Baseline sequencing detected mutations in all cases, with the major detected mutations being KMT2C (50%), CREBBP (45%), and KMT2D (45%). The concentration of ctDNA and tumor mutation burden showed a significant association with survival outcome. In particular, the presence of mutations in CREBBP and TP53 showed poor prognosis compared with patients without them. Longitudinal analysis of ctDNA using serially collected plasma samples showed an association between persistence or reappearance of ctDNA mutations and disease relapse or progression.
Conclusion
Analysis of ctDNA mutations in plasma at diagnosis might help predict outcome of disease, while analysis during follow-up may help to monitor disease status of patients with advanced FL. However, the feasibility of ctDNA measurement must be improved in order for it to become an appropriate and clinically relevant test in FL patients.

Citations

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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
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
Molecular Biomarkers in Prediction of High-Grade Transformation and Outcome in Patients with Follicular Lymphoma: A Comprehensive Systemic Review
Marie Hairing Enemark, Jonas Klejs Hemmingsen, Maja Lund Jensen, Robert Kridel, Maja Ludvigsen
International Journal of Molecular Sciences.2024; 25(20): 11179. CrossRef

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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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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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Pembrolizumab

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

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Incidence and Features of Lymphoid Proliferation and Lymphomas after Solid Organ or Hematopoietic Stem Cell Transplantation in a National Database Cohort: Seung Min Hahn, Myeongjee Lee, JongHoon Hyun, Sungmin Lim, Ji-Man Kang, Jong Gyun Ahn, Dong Jin Joo, Inkyung Jung, Kyong Ihn; Cancer Res Treat. 2024;56(1):305-313. Published online July 18, 2023; DOI: https://doi.org/10.4143/crt.2023.647

Abstract PDF Supplementary Material PubReader ePub: Purpose
Post-transplantation lymphoproliferative disorders (PTLDs) after hematopoietic stem transplantation (HCT) or solid organ transplantation (SOT) result in poorer outcomes, including death. There are limited large cohort data on the incidence and natural course of PTLD in Asians.
Materials and Methods
We investigated PTLD using Korean national health insurance claims data of 47,518 patients who underwent HCT or SOT in 2008-2020. Patient demographics, time and type of PTLD diagnosis, type of PTLD treatment, and death data were collected. We used Fine and Gray subdistribution hazard models to calculate the cumulative incidence and risk factors for PTLD.
Results
During median follow-up of 5.32 years, PTLD occurred in 294 of 36,945 SOT patients (0.79%) and 235 of 10,573 HCT patients (2.22%). Cumulative incidence of PTLD were 0.49% at 1 year, 1.02% at 5 years, and 1.50% at 10 years post-transplantation. Age < 20 years (subdistribution hazard ratio [SHR] of 1.67 in age 10-19, SHR 1.51 in age 0-9), HCT (SHR 3.02), heart transplantation (SHR 2.27), and liver transplantation (SHR 1.47) were significant risk factors for PTLD. The presence of PTLD was associated with an increased risk of death (hazard ratio of 2.84). Overall, 5-year survival of PTLD patients was 68.9% (95% confidence interval, 64.9 to 73.2).
Conclusion
We observed a steady increase in PTLD over 10 years after HCT or SOT in this large cohort study. Pediatric age group, HCT, liver transplantation, and heart transplantation were suggested to be risk factors for PTLD, and PTLD was associated with a higher risk of death.

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Circulating Tumor DNA Reflects Histologic and Clinical Characteristics of Various Lymphoma Subtypes: Jin Ju Kim, Hye Min Kim, Hongkyung Kim, Soo-Jeong Kim, Seung-Tae Lee, Jong Rak Choi, Saeam Shin, Doh Yu Hwang; Cancer Res Treat. 2024;56(1):314-323. Published online July 17, 2023; DOI: https://doi.org/10.4143/crt.2023.667

Abstract PDF Supplementary Material PubReader ePub

Purpose
We designed and evaluated the clinical performance of a plasma circulating tumor DNA (ctDNA) panel of 112 genes in various subtypes of lymphoma.
Materials and Methods
Targeted deep sequencing with an error-corrected algorithm was performed in ctDNA from plasma samples that were collected before treatment in 42 lymphoma patients. Blood buffy coat was utilized as a germline control. We evaluated the targeted gene panel using mutation detection concordance on the plasma samples with matched tissue samples analyzed the mutation profiles of the ctDNA.
Results
Next-generation sequencing analysis using matched tissue samples was available for 18 of the 42 patients. At least one mutation was detected in the majority of matched tissue biopsy samples (88.9%) and plasma samples (83.3%). A considerable number of mutations (40.4%) that were detected in the tissue samples were also found in the matched plasma samples. Majority of patients (21/42) were diffuse large B cell lymphoma patients. The overall detection rate of ctDNA in patients was 85.7% (36/42). The frequently mutated genes included PIM1, TET2, BCL2, KMT2D, KLHL6, HIST1H1E, and IRF8. A cutoff concentration (4,506 pg/mL) of ctDNA provided 88.9% sensitivity and 82.1% specificity to predict ctDNA mutation detection. The ctDNA concentration correlated with elevated lactate dehydrogenase level and the disease stage.
Conclusion
Our design panel can detect many actionable gene mutations, including those at low frequency. Therefore, liquid biopsy can be applied clinically in the evaluation of lymphoma patients, especially in aggressive lymphoma patients.

Citations

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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

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Lung and Thoracic cancer

First-Line Alectinib vs. Brigatinib in Advanced Non–Small Cell Lung Cancer with ALK Rearrangement: Real-World Data: Youngkyung Jeon, Sehhoon Park, Hyun Ae Jung, Jong-Mu Sun, Se-Hoon Lee, Jin Seok Ahn, Myung-Ju Ahn; Cancer Res Treat. 2024;56(1):61-69. Published online July 14, 2023; DOI: https://doi.org/10.4143/crt.2023.461

Abstract PDF PubReader ePub

Purpose
Alectinib and brigatinib are second-generation anaplastic lymphoma receptor tyrosine kinases (ALKs) that are widely used as first-line therapy for treating ALK-positive advanced non–small cell lung cancer (NSCLC). Given the lack of a head-to-head comparison of these drugs as first-line therapies, this retrospective observational study aimed to compare the real-world efficacy and safety of alectinib and brigatinib.
Materials and Methods
Patients who received alectinib or brigatinib as the first-line treatment for ALK-positive advanced NSCLC were evaluated for clinical outcomes of objective response rate (ORR), intracranial ORR, time to next treatment (TTNT), progression-free survival (PFS), overall survival (OS), and safety profiles.
Results
Of 208 patients who received either alectinib or brigatinib as a first-line treatment, 176 received alectinib and 32 received brigatinib. At the data cutoff point, the median follow-up duration was 16.5 months (95% confidence interval [CI], 14.7 to 18.3) in the brigatinib group and 27.5 months (95% CI, 24.6 to 30.4) in the alectinib group. The ORR was 92.5% with alectinib and 93.8% for brigatinib. The intracranial ORR rates were 92.7% (38/41) and 100% (10/10), respectively. The rate of PFS at 12 months was comparable between the alectinib group and the brigatinib groups (84.4% vs. 84.1%, p=0.64), and the median TTNT, PFS, and OS were not reached in either group. Treatment-related adverse events were usually mild, and treatment discontinuation due to adverse events was rare (alectinib 4.5% vs. brigatinib 6.25%).
Conclusion
Alectinib and brigatinib had similar clinical benefits when used as the first-line treatment of NSCLC patients with ALK rearrangement in the real world.

Citations

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Bridging the Gap between Trial Adverse Events and Real-World Data
Sang Hyuk Kim, Hyun Lee, Dong Won Park
Cancer Research and Treatment.2024; 56(3): 972. CrossRef
Real‐world evidence of brigatinib as second‐line treatment after crizotinib for ALK+ non‐small cell lung cancer using South Korean claims data (K‐AREAL)
Jeong Eun Lee, Jin Hyun Nam, Sun Hong Kwon, Bo Kyung Kim, Seung Min Ha
Cancer Medicine.2024;[Epub] CrossRef
Cost‐Effectiveness Analysis of Adjuvant Alectinib versus Platinum‐Based Chemotherapy in Resected ALK‐Positive Non‐Small‐Cell Lung Cancer in the Chinese Health Care System
Qiran Wei, Yifang Liang, Jiahui Mao, Xin Guan
Cancer Medicine.2024;[Epub] 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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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
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
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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

Abstract PDF Supplementary Material PubReader ePub: 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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Efficacy of Salvage Treatments in Relapsed or Refractory Diffuse Large B-Cell Lymphoma Including Chimeric Antigen Receptor T-Cell Therapy: A Systematic Review and Meta-Analysis: Jinchul Kim, Jinhyun Cho, Sang Eun Yoon, Won Seog Kim, Seok Jin Kim; Cancer Res Treat. 2023;55(3):1031-1047. Published online March 13, 2023; DOI: https://doi.org/10.4143/crt.2022.1658

Abstract PDF Supplementary Material PubReader ePub

Purpose
We intend to evaluate the efficacy of salvage treatments for relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL) through meta-analysis.
Materials and Methods
R/R DLBCL trials were divided into two groups based on eligibility for autologous stem-cell transplantation (ASCT), and meta-analysis of each group was performed. Random effects models were used to estimate the 1-year progression-free survival (PFS) rate, and chimeric antigen receptor (CAR) T-cell therapy was used as reference treatment.
Results
Twenty-six ASCT-eligible cohorts from 17 studies comprising 2,924 patients and 59 ASCT-ineligible cohorts from 53 studies comprising 3,617 patients were included in the pooled analysis. In the ASCT-eligible group, the pooled 1-year PFS rate was 0.40 (95% confidence interval [CI], 0.15 to 0.65) for the CAR T-cell group and 0.34 (95% CI, 0.30 to 0.37) for the group with chemotherapy followed by ASCT intention. The two treatments were not significantly different in meta-regression analysis. In the ASCT-ineligible group, the pooled 1-year PFS was 0.40 (95% CI, 0.35 to 0.46) for CAR T-cell, and the highest primary outcome was 0.47 (95% CI, 0.37 to 0.57) for the tafasitamab group. CAR T-cell therapy showed significantly better outcomes than chemotherapy and therapies based on ibrutinib, lenalidomide, and selinexor. However, loncastuximab, polatuzumab plus bendamustine and rituximab, and the tafasitamab group showed no different efficacy than CAR T-cell therapy after adjusting for median number of previous lines of treatment.
Conclusion
Although several regimens were crudely grouped for classification, CAR T-cell therapy did not outperform chemotherapy followed by ASCT in the second-line setting or several recently developed agents in the ASCT-ineligible setting.

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Polatuzumab vedotin combined with bendamustine and rituximab for relapsed/refractory diffuse large B-cell lymphoma: A systematic review protocol
Mohammadreza Eslami, Mahdi Mehrabi, Mehrdad Payandeh, Fakhredin Saba, Chen Li
PLOS ONE.2024; 19(8): e0308247. CrossRef
Targeting CD22 for B-cell hematologic malignancies
Jia Xu, Wenjing Luo, Chenggong Li, Heng Mei
Experimental Hematology & Oncology.2023;[Epub] CrossRef

6,753 View
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Sarcoma

Clinicopathological Analysis and Treatment of Adult Patients with Inflammatory Myofibroblastic Tumor: A 15-Year Single-Center Study: Xin Liu, Chengcheng Gong, Jieyun Zhang, Wanjing Feng, Yanjing Guo, Youzhou Sang, Chunmeng Wang, Yong Chen, Jian Wang, Lin Yu, Xiaowei Zhang, Zhiguo Luo; Cancer Res Treat. 2023;55(3):1001-1010. Published online March 3, 2023; DOI: https://doi.org/10.4143/crt.2022.894

Abstract PDF Supplementary Material PubReader ePub

Purpose
Inflammatory myofibroblastic tumor (IMT) is a rare mesenchymal malignancy that occurs primarily in children and adolescents. The clinical and pathological features of IMT in adult patients are not well understood.
Materials and Methods
We retrospectively searched for records of adult patients with IMT at Fudan University Shanghai Cancer Center from 2006 to 2021. Clinicopathological data, treatments, and outcomes were collected and analyzed.
Results
Thirty adult patients with IMT, mostly women (60.0%), were included. The median age of the patients was 38 (21-77). The most common primary site was abdominopelvic region (53.3%), followed by lungs (20.0%). Seven patients had an abdominal epithelioid inflammatory myofibroblast sarcoma (EIMS). The positivity rate of anaplastic lymphoma kinase (ALK) was 81.5% (22/27). Sixteen patients with advanced ALK-positive disease received crizotinib, with an objective response rate (ORR) of 81.3% and a disease control rate of 87.5%. The median progression-free survival was 20.8 months. EIMS was associated with more aggressive behavior; however, the prognosis was similar to that of non-EIMS patients after treatment with an ALK inhibitor. At a median follow-up time of 30 months (95% confidence interval [CI], 13.6 to 46.4), the 5-year overall survival was 77% (95% CI, 66 to 88) in all patients.
Conclusion
Adult IMTs appeared more aggressive, with a higher incidence of recurrence and metastases, and patients with EIMS had more aggressive cases. Treatment with ALK inhibitors resulted in a high ORR and a durable response, which suggested that ALK inhibitors could be used as a first-line treatment option in adult patients with ALK-positive advanced IMT.

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Inflammatory myofibroblastic tumor of the adrenal gland: A case report
Jiyao Yang, Hongjin Shi, Haifeng Wang, Yidao Liu
Urology Case Reports.2024; 55: 102763. CrossRef
Ibero-American Consensus for the Management of Peritoneal Sarcomatosis: Updated Review and Clinical Recommendations
Francisco Cristóbal Muñoz-Casares, Javier Martín-Broto, Pedro Cascales-Campos, Juan Torres-Melero, Irene López-Rojo, José Gómez-Barbadillo, Luis González-Bayón, Ana Sebio, César Serrano, Sara Carvalhal, Joaquim Abreu de Souza, Alexandre Souza, Guillermo F
Cancers.2024; 16(15): 2646. CrossRef
Thoracic epithelioid inflammatory myofibroblastic sarcoma: a rare and aggressive disease with case report and literature review
Linke Yang, Pei Li, Runze Liu, Baomin Feng, Huiqing Mao, Xiaoyong Tang, Guangjian Yang
Discover Oncology.2024;[Epub] CrossRef
Metastasized inflammatory myofibroblastic tumor of uterine origin
Thomas Bartl, Michael Deavers, Ryan Blair Kieser, Pedro T Ramirez
International Journal of Gynecologic Cancer.2024; 34(10): 1643. CrossRef
Epithelioid inflammatory myofibroblastic sarcoma with exceptionally long response to lorlatinib—a case report
Rafał Becht, Kajetan Kiełbowski, Justyna Żychowska, Wojciech Poncyljusz, Aleksandra Łanocha, Katarzyna Kozak, Ewa Gabrysz-Trybek, Paweł Domagała
Therapeutic Advances in Medical Oncology.2024;[Epub] CrossRef
Clinicopathological Characteristics of Inflammatory Myofibroblastic Tumor: A Single Center Retrospective Cohort Study
Xiaoyan Si, Shafei Wu, Ruie Feng, Mengzhao Wang, Hanping Wang, Xiaotong Zhang, Li Zhang, Kaifeng Xu
Thoracic Cancer.2024;[Epub] CrossRef
Rare giant epithelioid inflammatory myofibroblastic sarcoma of the abdominal cavity in a child: a case report and review of the literature
Jinzhou Li, Haixing Su, Sheng Zhang, Xianyun Chen, Chongzhi Hou, Tao Cheng
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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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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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

Abstract PDF PubReader ePub

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.

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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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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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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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Busulfan, Melphalan, and Etoposide (BuME) Showed an Equivalent Effect to Busulfan, Cyclophosphamide, and Etoposide (BuCE) as Conditioning Therapy for Autologous Stem Cell Transplantation in Patients with Relapsed or High-Risk Non-Hodgkin’s Lymphoma: A Multicenter Randomized Phase II Study bythe Consortium for Improving Survival of Lymphoma (CISL): Kyoung Ha Kim, Jae Hoon Lee, Mark Lee, Hoon-Gu Kim, Young Rok Do, Yong Park, Sung Yong Oh, Ho-Jin Shin, Won Seog Kim, Seong Kyu Park, Jee Hyun Kong, Moo-Rim Park, Deok-Hwan Yang, Jae-Yong Kwak, Hye Jin Kang, Yeung-Chul Mun, Jong-Ho Won; Cancer Res Treat. 2023;55(1):304-313. Published online March 30, 2022; DOI: https://doi.org/10.4143/crt.2022.004

Abstract PDF PubReader ePub

Purpose
High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is the standard management for relapsed or high-risk non-Hodgkin’s lymphoma (NHL). We reported the busulfan, melphalan, and etoposide (BuME) conditioning regimen was effective in patients with relapsed or high-risk NHL. Moreover, the busulfan, cyclophosphamide, and etoposide (BuCE) conditioning regimen has been used widely in ASCT for NHL. Therefore, based on these encouraging results, this randomized phase II multicenter trial compared the outcomes of BuME and BuCE as conditioning therapies for ASCT in patients with NHL.
Materials and Methods
Patients were randomly assigned to receive either BuME (n=36) or BuCE (n=39). The BuME regimen was comprised of busulfan (3.2 mg/kg/day, intravenously) administered on days –7, –6, and –5, etoposide (400 mg/m² intravenously) on days –5 and –4, and melphalan (50 mg/m2/day intravenously) on days –3 and –2. The BuCE regimen was comprised of busulfan (3.2 mg/kg/day intravenously) on days –7, –6, and –5, etoposide (400 mg/m²/day intravenously) on days –5 and –4, and cyclophosphamide (50 mg/kg/day intravenously) on days –3 and –2. The primary endpoint was 2-year progression-free survival (PFS).
Results
Seventy-five patients were enrolled. Eleven patients (30.5%) in the BuME group and 13 patients (33.3%) in the BuCE group had disease progression or died. The 2-year PFS rate was 65.4% in the BuME group and 60.6% in the BuCE group (p=0.746). There were no non-relapse mortalities within 100 days after transplantation.
Conclusion
There were no significant differences in PFS between the two groups. Therefore, busulfan-based conditioning regimens, BuME and BuCE, may be important treatment substitutes for the BCNU-containing regimens.

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CEAC (oral semustine, etoposide, cytarabine and cyclophosphamide) vs BEAM (carmustine, etoposide, cytarabine, and melphalan) conditioning regimen of autologous stem cell transplantation for diffuse large B-cell lymphoma: a post-hoc, propensity score-match
Tao Wang, Ping Liu, Lili Xu, Lei Gao, Xiong Ni, Gusheng Tang, Li Chen, Jie Chen, Libing Wang, Yang Wang, Weijia Fu, Wenqin Yue, Na Liu, Ruobing Li, Guihua Lu, Yanrong Luo, Jianmin Yang
Annals of Hematology.2024; 103(2): 575. 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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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
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
Clinical use of circulating tumor DNA analysis in patients with lymphoma
Bettina Bisig, Karine Lefort, Sylvain Carras, Laurence de Leval
Human Pathology.2024; : 105679. 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 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

Abstract PDF Supplementary Material PubReader ePub

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.

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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

Abstract PDF Supplementary Material PubReader ePub: 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.

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CNS cancer

Hypo-trimethylation of Histone H3 Lysine 4 and Hyper-tri/dimethylation of Histone H3 Lysine 27 as Epigenetic Markers of Poor Prognosis in Patients with Primary Central Nervous System Lymphoma: Hoon Gi Kim, Minseok S. Kim, Young Sam Lee, Eun Hee Lee, Dae Cheol Kim, Sung-Hun Lee, Young Zoon Kim; Cancer Res Treat. 2022;54(3):690-708. Published online November 17, 2021; DOI: https://doi.org/10.4143/crt.2021.1121

Abstract PDF Supplementary Material PubReader ePub

Purpose
This study aimed to investigate the methylation status of major histone modification sites in primary central nervous system lymphoma (PCNSL) samples and examine their prognostic roles in patients with PCNSL.
Materials and Method
Between 2007 and 2020, 87 patients were histopathologically diagnosed with PCNSL. We performed immunohistochemical staining of the formalin-fixed paraffin-embedded samples of PCNSL for major histone modification sites, such as H3K4, H3K9, H3K27, H3K14, and H3K36. After detection of meaningful methylation sites, we examined histone modification enzymes that induce methylation or demethylation at each site using immunohistochemical staining. The meaningful immunoreactivity was validated by western blotting using fresh tissue of PCNSL.
Results
More frequent recurrences were found in hypomethylation of H3K4me3 (p=0.004) and hypermethylation of H3K27me2 (p<0.001) and H3K27me3 (p=0.002). These factors were also statistically related to short PFS and overall survival in the univariate and multivariate analyses. Next, histone modification enzymes inducing the demethylation of H3K4 (lysine-specific demethylase-1/2 and Jumonji AT-rich interactive domain [JARID] 1A-D]) and methylation of H3K27 (enhancer of zeste homolog [EZH]-1/2) were immu- nohistochemically stained. Among them, the immunoreactivity of JARID1A inversely associated with the methylation status of H3K4me3 (R²=-1.431), and immunoreactivity of EZH2 was directly associated with the methylation status of H3K27me2 (R²=0.667) and H3K27me3 (R²=0.604). These results were validated by western blotting in fresh PCNSL samples.
Conclusion
Our study suggests that hypomethylation of H3K4me3 and hypermethylation of H3K27me2 and H3K27me3 could be associated with poor outcomes in patients with PCNSL and that these relationships are modified by JARID1A and EZH2.

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Updates of primary central nervous system lymphoma
Jiaying Wu, Delian Zhou, Xiaojian Zhu, Yicheng Zhang, Yi Xiao
Therapeutic Advances in Hematology.2024;[Epub] CrossRef
3-deazaneplanocin A, a histone methyltransferase inhibitor, improved the chemoresistance induced under hypoxia in melanoma cells
Mika Hosokawa, Sekai Tetsumoto, Mirano Yasui, Yusuke Kono, Ken-ichi Ogawara
Biochemical and Biophysical Research Communications.2023; 677: 26. CrossRef
Extranodal lymphoma: pathogenesis, diagnosis and treatment
Hua Yang, Yang Xun, Chao Ke, Kensuke Tateishi, Hua You
Molecular Biomedicine.2023;[Epub] CrossRef
Diagnostic and Therapeutic Perspectives Associated to Cobalamin-Dependent Metabolism and Transcobalamins’ Synthesis in Solid Cancers
Valentin Lacombe, Guy Lenaers, Geoffrey Urbanski
Nutrients.2022; 14(10): 2058. CrossRef
Primary central nervous system lymphoma: advances in its pathogenesis, molecular markers and targeted therapies
Isaias Hernández-Verdin, Andrea Morales-Martínez, Khê Hoang-Xuan, Agustí Alentorn
Current Opinion in Neurology.2022; 35(6): 779. CrossRef

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Pediatric cancer

Epidemiology of Acute Leukemia among Children with Down Syndrome in Korea: Young Bae Choi, Keon Hee Yoo; Cancer Res Treat. 2022;54(2):572-578. Published online August 10, 2021; DOI: https://doi.org/10.4143/crt.2021.368

Abstract PDF PubReader ePub

Purpose
Children with Down syndrome (DS) show a higher risk of acute leukemia than those without DS. In this study, we investigated the nationwide incidence of acute leukemia among children with DS and compared their epidemiologic characteristics with those of children with acute leukemia but without DS.
Materials and Methods
Using the National Health Insurance Service database, we selected patients with acute leukemia aged 0–19 years at diagnosis between 2007 and 2016.
Results
Among the 4,697 children with acute leukemia, 54 (1.1%) had DS. The median incidence rate of leukemia with DS by year was 1.3% (range, 0.2%–2.0%). Sixteen patients with acute lymphoblastic leukemia (ALL; 29.6%) and 36 with acute myeloid leukemia (AML; 66.7%) had DS. The DS group showed younger age at diagnosis than the non-DS group, and diagnosis of AML was more frequent in the DS group than in the non-DS group (3 years vs. 9 years, p<0.001; 66.7% vs. 32.4%, P<0.001, respectively). The 5-year overall survival was comparable between the DS and non-DS groups (88.0% vs. 81.9%, p=0.375). Among all the Koreans born between 2007 and 2008, the incidences of acute leukemia, ALL, and AML were 49.25, 20.75, and 163.38 times higher, respectively, in the DS group than in the non-DS group.
Conclusion
Our findings support the fact that the incidence of acute leukemia is higher among patients with DS than among those without DS in Korea. However, the DS and non-DS groups in this study had a comparable overall survival rate.

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Cancer risks related to intellectual disabilities: A systematic review
Amina Banda, Jenneken Naaldenberg, Aura Timen, Agnies van Eeghen, Geraline Leusink, Maarten Cuypers
Cancer Medicine.2024;[Epub] CrossRef

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Hematologic malignancy

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.

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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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Plasma Circulating Tumor DNA in Patients with Primary Central Nervous System Lymphoma: Sang Eun Yoon, Yeon Jeong Kim, Joon Ho Shim, Donghyun Park, Junhun Cho, Young Hyeh Ko, Woong-Yang Park, Yeung-Chul Mun, Kyoung Eun Lee, Duck Cho, Won Seog Kim, Seok Jin Kim; Cancer Res Treat. 2022;54(2):597-612. Published online July 23, 2021; DOI: https://doi.org/10.4143/crt.2021.752

Abstract PDF Supplementary Material PubReader ePub

Purpose
Analysis of circulating tumor DNA (ctDNA) in blood could allow noninvasive genetic analysis of primary tumors. Although there have been unmet needs for noninvasive methods in patients with primary central nervous system lymphoma (PCNSL), it is still not determined whether plasma ctDNA analysis could be useful for patients with PCNSL.
Materials and Methods
Targeted deep sequencing of 54 genes was performed in cell-free DNA isolated from plasma samples collected pretreatment, during treatment, and at the end of treatment in 42 consecutively diagnosed PCNSL patients between January 2017 and December 2018.
Results
Targeted sequencing of plasma cell-free DNA detected somatic mutations representing ctDNA in 11 cases (11/41, 27%). The detection of ctDNA was not related to the concentration of cell-free DNA or tumor volume. The mutation profiles of these 11 cases varied between patients. The most frequently mutated gene was PIM1 (4/11, 36.4%), whereas KMT2D, PIK3CA, and MYD88 were each observed in three patients (3/11, 27%). The mutations of 13 genes were concordantly found in primary tumor tissue and plasma ctDNA, giving a detection sensitivity of 45%. During the serial tracking of seven patients with complete response, the disappearance of ctDNA mutations was found in four patients, whereas three patients had detected ctDNA mutation at the end of treatment.
Conclusion
The plasma ctDNA mutation analysis still has limited value for surveillance and predicting treatment outcomes of PCNSL because the detection efficiency was lower than other systemic lymphomas. Thus, analytical platforms should be improved to overcome anatomical hurdles associated with PCNSL.

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Detection of circulating tumor DNA in plasma of patients with primary CNS lymphoma by digital droplet PCR
Yujie Zhong, Geok Wee Tan, Johanna Bult, Nick Veltmaat, Wouter Plattel, Joost Kluiver, Roelien Enting, Arjan Diepstra, Anke van den Berg, Marcel Nijland
BMC Cancer.2024;[Epub] CrossRef
Clinical implications of CSF-ctDNA positivity in newly diagnosed diffuse large B cell lymphoma
Jin-Hua Liang, Yi-Fan Wu, Hao-Rui Shen, Yue Li, Jun-Heng Liang, Rui Gao, Wei Hua, Chun-Yu Shang, Kai-Xin Du, Tong-Yao Xing, Xin-Yu Zhang, Chen-Xuan Wang, Liu-Qing Zhu, Yang W. Shao, Jian-Yong Li, Jia-Zhu Wu, Hua Yin, Li Wang, Wei Xu
Leukemia.2024; 38(7): 1541. CrossRef
Liquid biopsy for improving diagnosis and monitoring of CNS lymphomas: A RANO review
Lakshmi Nayak, Chetan Bettegowda, Florian Scherer, Norbert Galldiks, Manmeet Ahluwalia, Alexander Baraniskin, Louisa von Baumgarten, Jacoline E C Bromberg, Andrés J M Ferreri, Christian Grommes, Khê Hoang-Xuan, Julia Kühn, James L Rubenstein, Roberta Rudà
Neuro-Oncology.2024; 26(6): 993. 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
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
Circulating Tumor DNA Profiling for Detection, Risk Stratification, and Classification of Brain Lymphomas
Jurik A. Mutter, Stefan K. Alig, Mohammad S. Esfahani, Eliza M. Lauer, Jan Mitschke, David M. Kurtz, Julia Kühn, Sabine Bleul, Mari Olsen, Chih Long Liu, Michael C. Jin, Charles W. Macaulay, Nicolas Neidert, Timo Volk, Michel Eisenblaetter, Sebastian Raue
Journal of Clinical Oncology.2023; 41(9): 1684. CrossRef
Clinical applications of circulating tumor DNA in central nervous system lymphoma
Anna Katharina Foerster, Eliza M. Lauer, Florian Scherer
Seminars in Hematology.2023; 60(3): 150. CrossRef
Genetic Profiling of Cell-Free DNA in Liquid Biopsies: A Complementary Tool for the Diagnosis of B-Cell Lymphomas and the Surveillance of Measurable Residual Disease
Gloria Figaredo, Alejandro Martín-Muñoz, Santiago Barrio, Laura Parrilla, Yolanda Campos-Martín, María Poza, Laura Rufián, Patrocinio Algara, Marina De La Torre, Ana Jiménez Ubieto, Joaquín Martínez-López, Luis-Felipe Casado, Manuela Mollejo
Cancers.2023; 15(16): 4022. CrossRef
Asian variant intravascular large B-cell lymphoma with highly suspected central nervous system involvement: A case report
Yong-Pyo Lee, Seung-Myoung Son, Jihyun Kwon
World Journal of Clinical Cases.2023; 11(33): 8058. CrossRef
The Minimal Residual Disease Using Liquid Biopsies in Hematological Malignancies
Rafael Colmenares, Noemí Álvarez, Santiago Barrio, Joaquín Martínez-López, Rosa Ayala
Cancers.2022; 14(5): 1310. CrossRef

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Increased Risk of Diabetes after Definitive Radiotherapy in Patients with Indolent Gastroduodenal Lymphoma: Jong Yun Baek, Do Hoon Lim, Dongryul Oh, Heerim Nam, Jae J Kim, Jun Haeng Lee, Byung-Hoon Min, Hyuk Lee; Cancer Res Treat. 2022;54(1):294-300. Published online April 1, 2021; DOI: https://doi.org/10.4143/crt.2021.073

Abstract PDF Supplementary Material PubReader ePub

Purpose
This study aimed to evaluate the effect of radiotherapy (RT) on the risk of diabetes by assessing hemoglobin A1c (HbA1c) levels in patients with gastroduodenal indolent lymphoma.
Materials and Methods
This retrospective study included patients with stage I extranodal marginal zone lymphoma of the mucosa-associated lymphoid tissue or follicular lymphoma of the gastroduodenal region who were treated with Helicobacter pylori eradication and/or RT between 2000 and 2019 in our institution. Of total 79 patients with HbA1c test, 17 patients received RT (RT group), while 62 patients did not receive RT (control group). A diabetes-associated event (DAE) was defined as a ≥ 0.5% increase in HbA1c levels from baseline, and diabetes event (DE) were defined as HbA1c level of ≥ 6.5%.
Results
During the median follow-up of 49 months, no local failure occurred after RT and no patients died of lymphoma. The RT group had significantly higher risk for DAEs on univariable analysis (hazard ratio [HR], 4.18; 95% confidence interval [CI], 1.64 to 10.66; p < 0.01) and multivariable analysis (HR, 3.68; 95% CI, 1.42 to 9.56; p=0.01). Further, the DE risk was significantly higher in the RT group than in the control group (HR, 4.32; 95% CI, 1.08 to 17.30; p=0.04) and in patients with increased baseline HbA1c levels (HR, 35.83; 95% CI, 2.80 to 459.19; p=0.01). On multivariable analysis, RT significantly increased the risk of DEs (HR, 4.55; 95% CI, 1.08 to 19.19; p=0.04), even after adjusting baseline HbA1c level (HR, 40.97; 95% CI, 3.06 to 548.01; p=0.01).
Conclusion
Patients who received RT for gastroduodenal indolent lymphoma had an increased risk of diabetes compared to those who did not.

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CHARACTERISTICS OF ENDOCRINE COMPONENT OF PANCREAS AFTER ADMINISTRATION OF N-ACETYLCYSTEINE IN THE MODEL OF ACUTE RADIATION-INDUCED PANCREATITIS
Grigoriy Aleksandrovich Demyashkin, Dali Ibragimovna Ugurchieva, Vladislav Andreevich Yakimenko, Matvey Anatol'evich Vadyukhin
Ulyanovsk Medico-biological Journal.2024; (2): 166. CrossRef
ASSESSMENT OF THE INFLAMMATORY RESPONSE IN THE PANCREAS AFTER ADMINISTRATION OF N-ACETYL CYSTEINE IN A MODEL OF POST-RADIATION PANCREATITIS
G.A. Demyashkin, D.A. Atyakshin, D.I. Ugurchieva, V.A. Yakimenko, M.A. Vadyukhin, S.N. Koryakin
Molekulyarnaya Meditsina (Molecular medicine).2024; : 58. CrossRef
Lactobacillus gasseriCKCC1913 mediated modulation of the gut–liver axis alleviated insulin resistance and liver damage induced by type 2 diabetes
Shuaiming Jiang, Aijie Liu, Wenyao Ma, Xinlei Liu, Pengfei Luo, Meng Zhan, Xiaoli Zhou, Lihao Chen, Jiachao Zhang
Food & Function.2023; 14(18): 8504. CrossRef
Consumption of ultra-processed foods and risk of multimorbidity of cancer and cardiometabolic diseases: a multinational cohort study
Reynalda Cordova, Vivian Viallon, Emma Fontvieille, Laia Peruchet-Noray, Anna Jansana, Karl-Heinz Wagner, Cecilie Kyrø, Anne Tjønneland, Verena Katzke, Rashmita Bajracharya, Matthias B. Schulze, Giovanna Masala, Sabina Sieri, Salvatore Panico, Fulvio Ricc
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Risk of Diabetes Mellitus after Radiotherapy for Gastric Mucosa-Associated Lymphoid Tissue Lymphoma
Joongyo Lee, Hong In Yoon, Jihun Kim, Jaeho Cho, Kyung Hwan Kim, Chang-Ok Suh
Cancers.2022; 14(17): 4110. CrossRef

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Hematologic Malignancy

Prognostic Stratification of Patients with Burkitt Lymphoma Using Serum β2-microglobulin Levels: Hyung-Don Kim, Hyungwoo Cho, Shin Kim, Kyoungmin Lee, Eun Hee Kang, Jung Sun Park, Chan-Sik Park, Jooryung Huh, Jin Sook Ryu, Sang-Wook Lee, Dok-Hyun Yoon, Seok Jin Kim, Young Hyeh Ko, Won Seog Kim, Cheolwon Suh; Cancer Res Treat. 2021;53(3):847-856. Published online December 17, 2020; DOI: https://doi.org/10.4143/crt.2020.1060

Abstract PDF Supplementary Material PubReader ePub

Purpose
We aimed to investigate the prognostic value of serum β2-microglobulin for patients with Burkitt lymphoma (BL) and to propose a risk-stratifying classification system.
Materials and Methods
A prospective registry-based cohort study of BL patients treated with dose-intensive or effective dose-adjusted chemotherapies (n=81) was conducted. Survival outcomes were compared based on previously reported risk groups and/or serum β2-microglobulin levels. A risk-stratifying classification system incorporating serum β2-microglobulin levels was proposed and validated in an independent validation cohort (n=60).
Results
The median age was 47 years, and 57 patients (70.4%) were male. Patients with high serum β2-microglobulin levels (> 2 mg/L) had significantly worse progression-free survival (PFS) and overall survival (OS) (p < 0.01 for both). Serum β2-microglobulin levels further stratified patients in the low-risk and high-risk groups in terms of PFS (p=0.010 and p=0.044, respectively) and OS (p=0.014 and p=0.026, respectively). Multivariate analyses revealed that a high serum β2-microglobulin level (> 2 mg/L) was independently associated with a shorter PFS (hazards ratio [HR], 3.56; p=0.047) and OS (HR, 4.66; p=0.043). The new classification system incorporating the serum β2-microglobulin level allowed the stratification of patients into three distinct risk subgroups with 5-year OS rates of 100%, 89.5%, and 62.5%. In an independent cohort of BL, the system was validated by stratifying patients with different survival outcomes.
Conclusion
Serum β2-microglobulin level is an independent prognostic factor for BL patients. The proposed β2-microglobulin–based classification system could stratify patients with distinct survival outcomes, which may help define appropriate treatment approaches for individual patients.

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The clinical significance and prognostic value of serum beta-2 microglobulin in adult lymphoma-associated hemophagocytic lymphohistiocytosis: a multicenter analysis of 326 patients
Ze Jin, Yi Miao, Jie Zhang, Jing Zhang, Chunling Wang, Xuzhang Lu, Yuqing Miao, Miao Sun, Yunping Zhang, Yun Zhuang, Haiwen Ni, Jingyan Xu, Wanchuan Zhuang, Min Zhao, Jianfeng Zhu, Min Xu, Guoqiang Lin, Haiying Hua, Xiaoyan Xie, Maozhong Xu, Tao Jia, Liji
Annals of Hematology.2024; 103(7): 2257. 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
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Zhen-Yuan Liu, Feng Tang, Jin-Zhou Yang, Xi Chen, Ze-Fen Wang, Zhi-Qiang Li
Cellular and Molecular Neurobiology.2024;[Epub] CrossRef
Serum beta2-microglobulin acts as a biomarker for severity and prognosis in glioma patients: a preliminary clinical study
Zhen-Yuan Liu, Feng Tang, Jing Wang, Jin-Zhou Yang, Xi Chen, Ze-Fen Wang, Zhi-Qiang Li
BMC Cancer.2024;[Epub] CrossRef
Serum beta2-microglobulin and peripheral blood eosinophils for the assessment of severity and prognosis with omicron variant COVID-19 infection
Jie Tan, Hanxi Fang, Xiao Hu, Ming Yue, Junling Yang
Frontiers in Molecular Biosciences.2024;[Epub] CrossRef
A novel inflammation-related prognostic model for predicting the overall survival of primary central nervous system lymphoma: A real-world data analysis
Zhentian Wu, Chenyi Wang, Yao Lyu, Zheshen Lin, Ming Lu, Shixiong Wang, Bingxuan Wang, Na Yang, Yeye Li, Jianhong Wang, Xiaohui Duan, Na Zhang, Jing Gao, Yuan Zhang, Miaowang Hao, Zhe Wang, Guangxun Gao, Rong Liang
Frontiers in Oncology.2023;[Epub] CrossRef
Beta2-microglobulin is a valuable marker and identifies a poor-prognosis subgroup among intermediate-risk patients with diffuse large B cell lymphoma
Ning-Chun Chen, Hung Chang, Hsiao-Wen Kao, Che-Wei Ou, Ming-Chung Kuo, Po-Nan Wang, Tung-Liang Lin, Jin-Hou Wu, Yu-Shin Hung, Yi-Jiun Su, Yuen-Chin Ong, Hsuan-Jen Shih
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Tuberculosis combined with Burkitt lymphoma in a kidney transplant recipient: A case report and literature review
Jian-Nan Hu, Mu-Qing Yu, Li-Juan Hua, Chen Bao, Qian Liu, Chao Liu, Zi-Ling Li, Xi Wang, Shu-Yun Xu
Medicine.2023; 102(18): e33671. CrossRef
Elevated serum beta-2 microglobulin level predicts short-term poor prognosis of patients with de novo acute omicron variant COVID-19 infection
Shengping Gong, Ruishuang Ma, Ting Zhu, Xiaoqin Ge, Rongrong Xie, Qingsong Tao, Cong Shi
Frontiers in Cellular and Infection Microbiology.2023;[Epub] CrossRef
An Externally Validated Nomogram for Predicting the Overall Survival of Patients With Diffuse Large B-Cell Lymphoma Based on Clinical Characteristics and Systemic Inflammatory Markers
Yajiao Liu, Li Sheng, Haiying Hua, Jingfen Zhou, Ying Zhao, Bei Wang
Technology in Cancer Research & Treatment.2023;[Epub] CrossRef
Prognostic significance of serum β2-microglobulin levels in patients with peripheral T-cell lymphoma not otherwise specified
Hyung-Don Kim, Hyungwoo Cho, Byeong Seok Sohn, Chan-Sik Park, Jooryung Huh, Jin Sook Ryu, Sang-Wook Lee, Sang Eun Yoon, Seok Jin Kim, Young Hyeh Ko, Won Seog Kim, Cheolwon Suh
Leukemia & Lymphoma.2022; 63(1): 124. CrossRef

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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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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
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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
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EJNMMI Research.2021;[Epub] CrossRef

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Hematologic malignancy

Differing Outcomes of Patients with High Hyperdiploidy and ETV6-RUNX1 Rearrangement in Korean Pediatric Precursor B Cell Acute Lymphoblastic Leukemia: Jae Wook Lee, Seongkoo Kim, Pil-Sang Jang, Nack-Gyun Chung, Bin Cho; Cancer Res Treat. 2021;53(2):567-575. Published online October 8, 2020; DOI: https://doi.org/10.4143/crt.2020.507

Abstract PDF Supplementary Material PubReader ePub

Purpose
Recent cooperative trials in pediatric acute lymphoblastic leukemia (ALL) report long-term event-free survival (EFS) of greater than 80%. In this study, we analyzed the outcome and prognostic factors for patients with precursor B cell ALL (n=405) diagnosed during a 10-year period (2005-2015) at our institution.
Materials and Methods
All patients were treated with a uniform institutional regimen based on four risk groups, except for steroid type; patients diagnosed up till 2008 receiving dexamethasone, while subsequent patients received prednisolone. None of the patients received cranial irradiation in first complete remission.
Results
The 10-year EFS and overall survival was 76.3%±2.3% and 85.1%±1.9%. Ten-year cumulative incidence of relapse, any central nervous system (CNS) relapse and isolated CNS relapse was 20.8%±2.2%, 3.7%±1.1% and 2.5%±0.9% respectively. A comparison of established, good prognosis genetic abnormalities showed that patients with high hyperdiploidy had significantly better EFS than those with ETV6-RUNX1 rearrangement (10-year EFS of 91.2%±3.0% vs. 79.5%±4.4%, p=0.033). For the overall cohort, male sex, infant ALL, initial CNS involvement, and Philadelphia chromosome (+) ALL were significant factors for lower EFS in multivariate study, while high hyperdiploidy conferred favorable outcome. For high and very high risk patients (n=231), high hyperdiploidy was the only significant factor for EFS in multivariate study.
Conclusion
Regarding good prognosis genetic abnormalities, patients with high hyperdiploidy had significantly better outcome than ETV6-RUNX1 (+) patients. High hyperdiploidy was a major, favorable prognostic factor in the overall patient group, as well as the subgroup of patients with higher risk.

Citations

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Diagnostic and therapeutic advances in adults with acute lymphoblastic leukemia in the era of gene analysis and targeted immunotherapy
Jae-Ho Yoon, Seok Lee
The Korean Journal of Internal Medicine.2024; 39(1): 34. CrossRef
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Xinyu Li, Zaoli Huang, Liwen Zhu, Weixin Lai, Yunyao Li, Han Chen, Diandian Liu, Junjiu Huang, Dunhua Zhou, Yang Li, Wenjun Weng, Honggui Xu, Luhong Xu, Zhenhua Luo, Jianpei Fang
BMC Medical Genomics.2024;[Epub] CrossRef
Distinct Immunophenotypes in the DNA Index-Based Stratification of Pediatric B-Cell Acute Lymphoblastic Leukemia
Myriam Campos-Aguilar, Wilfrido David Tapia-Sánchez, Alberto Daniel Saucedo-Campos, Carlos Leonardo Duarte-Martínez, Sandra Olivas-Quintero, Almarosa Ruiz-Ochoa, Adolfo Rene Méndez-Cruz, Julia Reyes-Reali, María Isabel Mendoza-Ramos, Rafael Jimenez-Flores
Cancers.2024; 16(21): 3585. CrossRef
The Landscape of Secondary Genetic Rearrangements in Pediatric Patients with B-Cell Acute Lymphoblastic Leukemia with t(12;21)
Agnieszka Kaczmarska, Justyna Derebas, Michalina Pinkosz, Maciej Niedźwiecki, Monika Lejman
Cells.2023; 12(3): 357. CrossRef
Overview on Aneuploidy in Childhood B-Cell Acute Lymphoblastic Leukemia
Kinga Panuciak, Emilia Nowicka, Angelika Mastalerczyk, Joanna Zawitkowska, Maciej Niedźwiecki, Monika Lejman
International Journal of Molecular Sciences.2023; 24(10): 8764. CrossRef
Construction of three‐gene‐based prognostic signature and analysis of immune cells infiltration in children and young adults with B‐acute lymphoblastic leukemia
Chunli Xiang, Jie Wu, Liang Yu
Molecular Genetics & Genomic Medicine.2022;[Epub] CrossRef
Prognostic Value and Outcome for ETV6/RUNX1-Positive Pediatric Acute Lymphoblastic Leukemia: A Report From the South China Children’s Leukemia Group
Kun-yin Qiu, Hong-gui Xu, Xue-qun Luo, Hui-rong Mai, Ning Liao, Li-hua Yang, Min-cui Zheng, Wu-qing Wan, Xue-dong Wu, Ri-yang Liu, Qi-wen Chen, Hui-qin Chen, Xiao-fei Sun, Hua Jiang, Xing-jiang Long, Guo-hua Chen, Xin-yu Li, Chang-gang Li, Li-bin Huang, Y
Frontiers in Oncology.2021;[Epub] CrossRef

7,112 View
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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

Abstract PDF Supplementary Material PubReader ePub

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

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Chen Li, Xiao Chang, Qifeng Wang, Qingsong Pang, Zefen Xiao, Wencheng Zhang, Zhiyong Yuan
Therapeutic Advances in Medical Oncology.2024;[Epub] CrossRef
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
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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

6,935 View
110 Download
3 Web of Science
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