Cancer Research and Treatment

Original Articles

Hematologic malignancy

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

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

2,151 View
160 Download

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.

4,995 View
269 Download

Clinical Significance of bZIP In-Frame CEBPA-Mutated Normal Karyotype Acute Myeloid Leukemia: Seo-Yeon Ahn, TaeHyung Kim, Mihee Kim, Ga-Young Song, Sung-Hoon Jung, Deok-Hwan Yang, Je-Jung Lee, Mi Yeon Kim, Chul Won Jung, Jun-Ho Jang, Hee Je Kim, Joon Ho Moon, Sang Kyun Sohn, Jong-Ho Won, Sung-Hyun Kim, Hyeoung-Joon Kim, Jae-Sook Ahn, Dennis Dong Hwan Kim; Cancer Res Treat. 2023;55(3):1011-1022. Published online January 26, 2023; DOI: https://doi.org/10.4143/crt.2022.1407

Abstract PDF PubReader ePub

Purpose
We evaluated the characteristics of CCAAT/enhancer-binding protein α (CEBPA) mutations and the significance of a basic leucine zipper in-frame mutation (bZIP^in-f) of CEBPA in patients with acute myeloid leukemia with a normal karyotype.
Materials and Methods
Based on updated knowledge of CEBPA mutations, we conducted next-generation sequencing analyses in a previously established real-world cohort.
Results
Among 78 of a total of 395 patients (19.7%), 50 had bZIP^in-f CEBPA, and 28 had non-bZIP^in-f CEBPA. In the multivariate analysis, patients with NPM1^mut, those with bZIP^in-f CEBPA, and those who underwent allogeneic hematopoietic cell transplantation (allo-HCT) had favorable overall survival (OS), but FLT3-ITD^mut was a poor prognostic indicator. For relapse-free survival (RFS) and cumulative incidence of relapse, bZIP^in-f CEBPA, and allo-HCT were associated with favorable outcomes; FLT3-ITD^pos was associated with worse outcomes. In the CEBPA double-mutated group (CEBPA^dm), bZIP^in-f CEBPA was associated with superior outcomes in terms of OS (p=0.007) and RFS (p=0.007) compared with non-bZIP^in-f CEBPA. Of 50 patients with bZIP^in-f CEBPA, 36 patients had at least one mutation. When grouped by the presence of mutations in chromatic/DNA modifiers (C), cohesion complex (C), and splicing genes (S) (CCS mutations), CCS-mutated bZIP^in-f CEBPA was associated with poor OS (p=0.044; hazard ratio [HR], 2.419) and a trend in inferior RFS (p=0.186; HR, 1.838).
Conclusion
Only bZIP^in-f CEBPA was associated with favorable outcomes in patients with CEBPA^dm. However, some mutations accompanying bZIP^in-f CEBPA showed inferior OS; thus, further studies with larger numbers of patients are required for clear conclusions of the significance of bZIP^in-f CEBPA.

Citations

Citations to this article as recorded by

Prognostic value of CEBPA bZIP signatures in cytogenetically normal acute myeloid leukaemia
Li‐Xin Wu, Ming‐Yue Liao, Ming‐Yue Zhao, Nan Yan, Ping Zhang, Li‐Xia Liu, Jia‐Yue Qin, Shan‐Bo Cao, Jia Feng, Qian Jiang, Ying‐Jun Chang, Lan‐Ping Xu, Xiao‐Hui Zhang, Xiao‐Jun Huang, Hao Jiang, Hong‐Yu Zhang, Guo‐Rui Ruan
British Journal of Haematology.2025;[Epub] CrossRef
CEBPA double mutations associated with ABO antigen weakness in hematologic diseases
Seung Jun Choi, Hyun Kyung Kim, Eun Jung Suh, Soon Sung Kwon, Saeam Shin, Seung-Tae Lee, Sinyoung Kim
Blood Advances.2024; 8(6): 1487. CrossRef
CEBPA bZIP in-frame mutations in acute myeloid leukemia: prognostic and therapeutic implications
Fenghong Zhang, Zhen Shen, Jundan Xie, Jingren Zhang, Qian Wu, Rui Jiang, Xiangyu Zhao, Xiaofei Yang, Suning Chen
Blood Cancer Journal.2024;[Epub] CrossRef
Mutations in the bZip region of the CEBPA gene: A novel prognostic factor in patients with acute myeloid leukemia
Juan Carlos Rivera, Daniel Nuñez, Elizabet Millar, Kimberly Ramirez, Mauricio Chandía, Claudio Aguayo
International Journal of Laboratory Hematology.2023; 45(6): 833. CrossRef

5,497 View
252 Download
4 Web of Science
4 Crossref

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.

Citations

Citations to this article as recorded by

PI3Kδ inhibitor linperlisib combined with gemcitabine and oxaliplatin for relapsed or refractory diffuse large B-cell lymphoma: a multicenter, single-arm phase Ib/II trial
Peng Sun, Hong Cen, Haiyan Yang, Rui Huang, Zhen Cai, Xuekui Gu, Hanying Bao, Zusheng Xu, Zuhong Xu, Zhi-Ming Li
Cancer Cell International.2025;[Epub] CrossRef
Improving access to chimeric antigen receptor T-cells for refractory or relapsing diffuse large B cell lymphoma therapy in Asia
Ya Hwee Tan, Dok Hyun Yoon, Andrew J. Davies, Christian Buske, Yang Liang Boo, Nagavalli Somasundaram, Francesca Lim, Shin Yeu Ong, Anand Jeyasekharan, Koji Izutsu, Won Seog Kim, Jason Yongsheng Chan
Discover Oncology.2025;[Epub] CrossRef
Recent advances in cellular immunotherapy for lymphoid malignancies
Haerim Chung, Hyunsoo Cho
Blood Research.2023; 58(4): 166. CrossRef
Sphingosine 1-phosphate receptor, a new therapeutic direction in different diseases
Hongyu Chen, Junmin Wang, Caiyun Zhang, Peilun Ding, Shuxia Tian, Junming Chen, Guang Ji, Tao Wu
Biomedicine & Pharmacotherapy.2022; 153: 113341. CrossRef

8,119 View
367 Download
3 Web of Science
4 Crossref

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.

Citations

Citations to this article as recorded by

Shorting of existing conditioning regimen for relapsed/refractory gastric diffuse large B-cell lymphoma transplant and studying its related outcomes: A first of its kind case report
Priyatesh Chandra Dwivedi, Yasam Venkata Ramesh, Raj Nagarkar
Iraqi Journal of Hematology.2025;[Epub] CrossRef
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

6,169 View
237 Download
1 Web of Science
2 Crossref

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.

8,169 View
304 Download
1 Web of Science

Clinical Outcome of Rituximab-Based Therapy (RCHOP) in Diffuse Large B-Cell Lymphoma Patients with Bone Marrow Involvement: Byung Woog Kang, Joon Ho Moon, Yee Soo Chae, Soo Jung Lee, Jong Gwang Kim, Yeo-Kyeoung Kim, Je-Jung Lee, Deok-Hwan Yang, Hyeoung-Joon Kim, Jin Young Kim, Young Rok Do, Keon Uk Park, Hong Suk Song, Ki Young Kwon, Min Kyung Kim, Kyung Hee Lee, Myung Soo Hyun, Hun Mo Ryoo, Sung Hwa Bae, Hwak Kim, Sang Kyun Sohn; Cancer Res Treat. 2013;45(2):112-117. Published online June 30, 2013; DOI: https://doi.org/10.4143/crt.2013.45.2.112

Abstract PDF PubReader ePub

PURPOSE
We investigated the clinical outcome of bone marrow (BM) involvement in patients with diffuse large B-cell lymphoma (DLBCL) who received rituximab-based therapy.
MATERIALS AND METHODS
A total of 567 consecutive patients with newly diagnosed DLBCL treated with rituximab-CHOP (RCHOP) between November 2001 and March 2010 were included in the current study. All of the patients underwent a BM study at the initial staging and the clinical characteristics and prognosis of these patients with or without BM involvement were analyzed retrospectively.
RESULTS
The total cohort included 567 patients. The overall incidence of BM involvement was 8.5%. With a median follow-up duration of 33.2 months (range, 0.1 to 80.7 months) for patients who were alive at the last follow-up, the five-year overall survival (OS) and event-free survival (EFS) rate in patients without BM involvement (76.3% and 67.5%, p<0.001) was statistically higher than that in patients with BM involvement (44.3% and 40.1%, p<0.001). In multivariate analysis, among total patients, BM involvement showed a significant association with OS and EFS. In univariate and multivariate analyses, even among stage IV patients, a significant association with worse EFS was observed in the BM involvement group.
CONCLUSION
BM involvement at diagnosis affected the survival of patients with DLBCL who received RCHOP. Although use of RCHOP can result in significant improvement of the therapeutic effect of DLBCL, BM involvement is still a negative prognostic factor of DLBCL patients in the era of rituximab.

Citations

Citations to this article as recorded by

Combination of Bone Marrow Biopsy and Flow Cytometric Analysis: The Prognostically Relevant Central Approach for Detecting Bone Marrow Invasion in Diffuse Large B-Cell Lymphoma
Haruya Okamoto, Nobuhiko Uoshima, Ayako Muramatsu, Reiko Isa, Takahiro Fujino, Yayoi Matsumura-Kimoto, Taku Tsukamoto, Shinsuke Mizutani, Yuji Shimura, Tsutomu Kobayashi, Eri Kawata, Hitoji Uchiyama, Junya Kuroda
Diagnostics.2021; 11(9): 1724. CrossRef
Assessment of CD52 expression in "double-hit" and "double-expressor" lymphomas: Implications for clinical trial eligibility
Jeffrey W. Craig, Michael J. Mina, Jennifer L. Crombie, Ann S. LaCasce, David M. Weinstock, Geraldine S. Pinkus, Olga Pozdnyakova, Francesco Bertolini
PLOS ONE.2018; 13(7): e0199708. CrossRef
HIV-infection impact on clinical–biological features and outcome of diffuse large B-cell lymphoma treated with R-CHOP in the combination antiretroviral therapy era
Maria Joao Baptista, Olga Garcia, Mireia Morgades, Eva Gonzalez-Barca, Pilar Miralles, Armando Lopez-Guillermo, Eugenia Abella, Miriam Moreno, Juan-Manuel Sancho, Evarist Feliu, Josep-Maria Ribera, Jose-Tomas Navarro
AIDS.2015; 29(7): 811. CrossRef
Non-Hodgkin Lymphomas: Impact of Rituximab on Overall Survival of Patients with Diffuse Large B-Cell and Follicular Lymphoma
José Carlos Jaime-Pérez, Carmen Magdalena Gamboa-Alonso, Alberto Vázquez-Mellado de Larracoechea, Marisol Rodríguez-Martínez, César Homero Gutiérrez-Aguirre, Luis Javier Marfil-Rivera, David Gómez-Almaguer
Archives of Medical Research.2015; 46(6): 454. CrossRef

25,216 View
63 Download
4 Crossref

Alpha-Type 1 Polarized Dendritic Cells Loaded with Apoptotic Allogeneic Breast Cancer Cells Can Induce Potent Cytotoxic T Lymphocytes against Breast Cancer: Min-Ho Park, Deok-Hwan Yang, Mi-Hyun Kim, Jae-Hong Jang, Yoon-Young Jang, Youn-Kyung Lee, Chun-Ji Jin, Than Nhan Nguyen Pham, Truc Anh Nguyen Thi, Mi-Seon Lim, Hyun-Ju Lee, Cheol Yi Hong, Jung-Han Yoon, Je-Jung Lee; Cancer Res Treat. 2011;43(1):56-66. Published online March 31, 2011; DOI: https://doi.org/10.4143/crt.2011.43.1.56

Abstract PDF PubReader ePub

PURPOSE
Various tumor antigens can be loaded onto dendritic cells (DCs) to induce a potent cytotoxic T lymphocyte (CTL) response in DC-based immunotherapy against breast cancer. However, in the clinical setting, obtaining a sufficient number of autologous tumor cells as a source of tumor antigens is a laborious process. We therefore investigated the feasibility of immunotherapy using breast-cancer-specific CTLs generated in vitro by use of alpha-type 1 polarized DCs (alpha DC1s) loaded with ultraviolet B-irradiated cells of the breast cancer cell line MCF-7.
MATERIALS AND METHODS
alphaDC1s were induced by loading allogeneic tumor antigen generated from the MCF-7 UVB-irradiated breast cancer cell line. Antigen-pulsed alphaDC1s were evaluated by morphological and functional assays, and the breast-cancer-specific CTL response was analyzed by cytotoxic assay.
RESULTS
The alphaDC1s significantly increased the expression of several molecules related to DC maturation without differences according to whether the alphaDC1s were loaded with tumor antigens. The alphaDC1s showed a high production of interleukin-12 both during maturation and after subsequent stimulation with CD40L, which was not significantly affected by loading with tumor antigens. Breast-cancer-specific CTLs against autologous breast cancer cells were successfully induced by alphaDC1s loaded with apoptotic MCF-7 cells.
CONCLUSION
Autologous DCs loaded with an allogeneic breast cancer cell line can generate potent breast-cancer-specific CTL responses. This may be a practical method for cellular immunotherapy in patients with breast cancer.

Citations

Citations to this article as recorded by

Usefulness of IL-21, IL-7, and IL-15 conditioned media for expansion of antigen-specific CD8+ T cells from healthy donor-PBMCs suitable for immunotherapy
Julián A. Chamucero-Millares, David A. Bernal-Estévez, Carlos A. Parra-López
Cellular Immunology.2021; 360: 104257. CrossRef
Extending traditional antibody therapies: Novel discoveries in immunotherapy and clinical applications
Charles Shin, Sung Soo Kim, Yong Hwa Jo
Molecular Therapy - Oncolytics.2021; 22: 166. CrossRef
Enhanced Human T Lymphocyte Antigen Priming by Cytokine-Matured Dendritic Cells Overexpressing Bcl-2 and IL-12
Hui Zhang, Yu Wang, Qian-Ting Wang, Sheng-Nan Sun, Shi-You Li, Hong Shang, You-Wen He
Frontiers in Cell and Developmental Biology.2020;[Epub] CrossRef
Tumor lysate-loaded Bacterial Ghosts as a tool for optimized production of therapeutic dendritic cell-based cancer vaccines
N. Dobrovolskienė, V. Pašukonienė, A. Darinskas, J.A. Kraśko, K. Žilionytė, A. Mlynska, Ž. Gudlevičienė, E. Mišeikytė-Kaubrienė, V. Schijns, W. Lubitz, P. Kudela, M. Strioga
Vaccine.2018; 36(29): 4171. CrossRef
Antitumor dendritic cell–based vaccines: lessons from 20 years of clinical trials and future perspectives
João Constantino, Célia Gomes, Amílcar Falcão, Maria T. Cruz, Bruno M. Neves
Translational Research.2016; 168: 74. CrossRef
Identification of proteins derived from Listeria monocytogenes inducing human dendritic cell maturation
Reza Mirzaei, Azad Saei, Fatemeh Torkashvand, Bahareh Azarian, Ahmad Jalili, Farshid Noorbakhsh, Behrouz Vaziri, Jamshid Hadjati
Tumor Biology.2016; 37(8): 10893. CrossRef
Dendritic Cell-Based Cancer Immunotherapy against Multiple Myeloma: From Bench to Clinic
My-Dung Hoang, Sung-Hoon Jung, Hyun-Ju Lee, Youn-Kyung Lee, Thanh-Nhan Nguyen-Pham, Nu-Ri Choi, Manh-Cuong Vo, Seung-Shin Lee, Jae-Sook Ahn, Deok-Hwan Yang, Yeo-Kyeoung Kim, Hyeoung-Joon Kim, Je-Jung Lee
Chonnam Medical Journal.2015; 51(1): 1. CrossRef
Dendritic Cells Induce Specific Cytotoxic T Lymphocytes against Prostate Cancer TRAMP-C2 Cells Loaded with Freeze-thaw Antigen and PEP-3 Peptide
Xiao-Qi Liu, Rong Jiang, Si-Qi Li, Jing Wang, Fa-Ping Yi
Asian Pacific Journal of Cancer Prevention.2015; 16(2): 571. CrossRef
Branched Polyethylenimine-Superparamagnetic Iron Oxide Nanoparticles (bPEI-SPIONs) Improve the Immunogenicity of Tumor Antigens and Enhance Th1 Polarization of Dendritic Cells
My-Dung Hoang, Hwa-Jeong Lee, Hyun-Ju Lee, Sung-Hoon Jung, Nu-Ri Choi, Manh-Cuong Vo, Thanh-Nhan Nguyen-Pham, Hyeoung-Joon Kim, In-Kyu Park, Je-Jung Lee
Journal of Immunology Research.2015; 2015: 1. CrossRef
Generation of Potent Cytotoxic T Lymphocytes Against Castration‐Resistant Prostate Cancer Cells by Dendritic Cells Loaded With Dying Allogeneic Prostate Cancer Cells
E. C. Hwang, M.‐S. Lim, C.‐M. Im, D.‐D. Kwon, H.‐J. Lee, T.‐N. Nguyen‐Pham, Y.‐K. Lee, J.‐J. Lee
Scandinavian Journal of Immunology.2013; 77(2): 117. CrossRef
Dendritic Cell Engineering for Tumor Immunotherapy: from Biology to Clinical Translation
Arpit Bhargava, Dinesh Mishra, Smita Banerjee, Pradyumna Kumar Mishra
Immunotherapy.2012; 4(7): 703. CrossRef

12,324 View
54 Download
11 Crossref

Coexisting with Clonal Evolution and BCR-ABL Mutant in CML Patients Treated with Second-generation Tyrosine Kinase Inhibitors Predict the Discrepancy of in vitro Drug Sensitivity: Jae-Sook Ahn, Yeo-Kyeoung Kim, Se Ryeon Lee, Li Yu, Deok-Hwan Yang, Sang-Hee Cho, Hyun Jeong Shim, Woo Kyun Bae, Je-Jung Lee, Ik-Joo Chung, Myung Gun Shin, Hyeoung-Joon Kim; Cancer Res Treat. 2010;42(1):37-41. Published online March 31, 2010; DOI: https://doi.org/10.4143/crt.2010.42.1.37

Abstract PDF PubReader ePub

Purpose

Second-generation tyrosine kinase inhibitors (second TKIs) such as nilotinib and dasatinib control the activity of most ABL kinase domain mutations observed in patients with imatinib resistance. Although in vitro data show that both agents can inhibit all mutations except T315I, some discrepancies have been observed in a small subset of mutation clones. Cytogenetic clonal evolution is the important resistance mechanism of chronic myeloid leukemia (CML). Accordingly, we observed the clinical significance of coexisting with clonal evolution and BCR-ABL mutant in CML patients treated with second TKIs.

Materials and Methods

We monitored BCR-ABL transcript kinetics, interrelationship of clones expressing non-mutated and mutant transcripts and clonal aberrations within Philadelphia (Ph) positive and negative clones, respectively, in eight patients with CML receiving dasatinib or nilotinib for 3~41 months.

Results

Clinical responses were correlated with in vitro sensitivity of the BCR-ABL mutants to the second TKIs in four patients. Four patients showed resistance to the second TKIs as compared to in vitro observations; three of them developed chromosomal abnormalities in the Ph chromosome positive or negative metaphases. Another patient lost the original mutation but acquired a more resistant new mutation and became resistant to the second TKI.

Conclusion

Cytogenetic clonal evolution is an independent poor prognostic factor in CML, which could explain the onset of mechanisms for second TKIs resistance to ABL kinase domain mutations. The results indicate that an additional evaluation of chromosomal abnormalities is warranted when BCR-ABL mutants are more resistant than indicated by in vitro data.

Citations

Citations to this article as recorded by

T315I – a gatekeeper point mutation and its impact on the prognosis of chronic myeloid leukemia
Bushra Kaleem, Sadaf Shahab, Tahir Sultan Shamsi
Advances in Laboratory Medicine / Avances en Medicina de Laboratorio.2024; 5(4): 412. CrossRef
Impacto de la mutación T315I en el pronóstico de la leucemia mieloide crónica
Bushra Kaleem, Sadaf Shahab, Tahir Sultan Shamsi
Advances in Laboratory Medicine / Avances en Medicina de Laboratorio.2024; 5(4): 418. CrossRef
BCR-ABL1 mutation development during first-line treatment with dasatinib or imatinib for chronic myeloid leukemia in chronic phase
T P Hughes, G Saglio, A Quintás-Cardama, M J Mauro, D-W Kim, J H Lipton, M B Bradley-Garelik, J Ukropec, A Hochhaus
Leukemia.2015; 29(9): 1832. CrossRef

10,884 View
53 Download
3 Crossref

Optimization and Limitation of Calcium Ionophore to Generate DCs from Acute Myeloid Leukemic Cells: Thanh-Nhan Nguyen Pham, Bo-Hwa Choi, Hyun-Kyu Kang, Chun-Chi Jin, Nguyen Hoang Tuyet Minh, Sang-Ki Kim, Jong-Hee Nam, Deok-Hwan Yang, Yeo-Kyeoung Kim, Hyeoung-Joon Kim, Ik-Joo Chung, Je-Jung Lee; Cancer Res Treat. 2007;39(4):175-180. Published online December 31, 2007; DOI: https://doi.org/10.4143/crt.2007.39.4.175

Abstract PDF PubReader ePub

Purpose

Calcium ionophore (CI) is used to generate dendritic cells (DCs) from progenitor cells, monocytes, or leukemic cells. The aim of this study was to determine the optimal dose of CI and the appropriate length of cell culture required for acute myeloid leukemia (AML) cells and to evaluate the limitations associated with CI.

Materials and Methods

To generate leukemic DCs, leukemic cells (4×10⁶ cells) from six AML patients were cultured with various concentrations of CI and/or IL-4 for 1, 2 or 3 days.

Results

Potent leukemic DCs were successfully generated from all AML patients, with an average number of 1.2×10⁶ cells produced in the presence of CI (270 ng/ml) for 2 days. Several surface molecules were clearly upregulated in AML cells supplemented with CI and IL-4, but not CD11c. Leukemic DCs cultured with CI had a higher allogeneic T cell stimulatory capacity than untreated AML cells, but the addition of IL-4 did not augment the MLR activity of these cells. AML cells cultured with CI in the presence or absence of IL-4 showed increased levels of apoptosis in comparison to primary cultures of AML cells.

Conclusion

Although CI appears to be advantageous in terms of time and cost effectiveness, the results of the present study suggest that the marked induction of apoptosis by CI limits its application to the generation of DCs from AML cells.

Citations

Citations to this article as recorded by

The plasticity and potential of leukemia cell lines to differentiate into dendritic cells
QINGWEI GUO, LELING ZHANG, FU LI, GUOSHENG JIANG
Oncology Letters.2012; 4(4): 595. CrossRef

9,395 View
55 Download
1 Crossref

The Efficacy of an Induction Chemotherapy Combination with Docetaxel, Cisplatin, and 5-FU Followed by Concurrent Chemoradiotherapy in Advanced Head and Neck Cancer: Jae-Sook Ahn, Sang-Hee Cho, Ok-Ki Kim, Joon-Kyoo Lee, Deok-Hwan Yang, Yeo-Kyeoung Kim, Je-Jung Lee, Sang-Chul Lim, Hyeoung-Joon Kim, Woong-Ki Chung, Ik-Joo Chung; Cancer Res Treat. 2007;39(3):93-98. Published online September 30, 2007; DOI: https://doi.org/10.4143/crt.2007.39.3.93

Abstract PDF PubReader ePub

Purpose

This study was performed to determine the feasibility and safety of the use of induction chemotherapy combined with docetaxel, cisplatin, and 5-fluorouracil (TPF) followed by concurrent chemoradiation therapy for locally advanced squamous cell carcinoma of the head and neck (SCCHN).

Materials and Methods

The patients, that were initially not treated for locally advanced SCCHN, underwent three cycles of induction chemotherapy every 3 weeks at a dose of 70 mg/m² docetaxel D1, 75 mg/m² cisplatin D1, 1000 mg/m² 5-FU D1-4, and subsequently received concurrent chemoradiation therapy.

Results

Forty-nine patients were enrolled in this study and forty-three of the patients completed the treatment. The median duration of follow-up was 18 months (range, 6~39 months). All of the patients had stage III (26.5%) or IV (73.5%) squamous cell carcinoma. After sequential therapy, a complete response and partial response was seen in 28 (65.2%) and 13 (30.2%) patients, respectively. The overall response rate was 95.4%. Overall survival and progression-free survival (PFS) at 2 years were 88.7% and 69.7%, respectively. Grade 3~4 neutropenia occurred in 42.2% of the patients and grade 4 thrombocytopenia in 1 cycle (0.7%). Two patients (4.1%) died during the induction chemotherapy due to pneumonia and a subdural hemorrhage, respectively. The group of patients over 65 years of age showed a significant lower dose intensity than that of patients under 65 years of age, but PFS was not significantly different between two groups (p=0.105).

Conclusion

TPF induction chemotherapy followed by concurrent chemoradiotherapy showed a high level of CR and moderate treatment-induced toxicity. Adequate dose modification in elderly patients should be considered to maintain efficacy and avoid treatment-related toxicity.

Citations

Citations to this article as recorded by

Extended follow-up of a phase 2 trial of xevinapant plus chemoradiotherapy in high-risk locally advanced squamous cell carcinoma of the head and neck: a randomised clinical trial
Yungan TAO, Xu-Shan Sun, Yoann Pointreau, Christophe Le Tourneau, Christian Sire, Marie-Christine Kaminsky, Alexandre Coutte, Marc Alfonsi, Benôit Calderon, Pierre Boisselier, Laurent Martin, Jessica Miroir, Jean-Francois Ramee, Jean-Pierre Delord, Floria
European Journal of Cancer.2023; 183: 24. CrossRef
Serum Levels of Stromal Cell-Derived Factor-1α and Vascular Endothelial Growth Factor Predict Clinical Outcomes in Head and Neck Squamous Cell Carcinoma Patients Receiving TPF Induction Chemotherapy
Yen-Hao Chen, Chih-Yen Chien, Yu-Ming Wang, Shau-Hsuan Li
Biomedicines.2022; 10(4): 803. CrossRef
Dose-dense TPF induction chemotherapy for locally advanced head and neck cancer: a phase II study
Ching-Yun Hsieh, Ming-Yuh Lein, Shih-Neng Yang, Yao-Ching Wang, Yin-Jun Lin, Chen-Yuan Lin, Chun-Hung Hua, Ming-Hsul Tsai, Ching-Chan Lin
BMC Cancer.2020;[Epub] CrossRef
Neutrophil lymphocyte ratio is an independent prognosticator in patients with locally advanced head and neck squamous cell carcinoma receiving induction chemotherapy with docetaxel, cisplatin, and fluorouracil
Hsiang-Lan Lai, Yeh Tang, Chih-Yen Chien, Fu-Min Fang, Tai-Lin Huang, Tai-Jan Chiu, Shau-Hsuan Li
Journal of Cancer Research and Practice.2019; 6(4): 170. CrossRef
Influence of a dosing-time on toxicities induced by docetaxel, cisplatin and 5-fluorouracil in patients with oral squamous cell carcinoma; a cross-over pilot study
Yoshiyuki Tsuchiya, Kentaro Ushijima, Tadahide Noguchi, Naruo Okada, Jun-ichi Hayasaka, Yoshinori Jinbu, Hitoshi Ando, Yoshiyuki Mori, Mikio Kusama, Akio Fujimura
Chronobiology International.2018; 35(2): 289. CrossRef
Feasibility of concurrent chemoradiotherapy with high-dose cisplatin after induction TPF chemotherapy in head and neck cancer: a critical review of the literature and the experience of the European Institute of Oncology
D. Alterio, M. Cossu Rocca, W. Russell-Edu, S. Dicuonzo, G. Fanetti, G. Marvaso, L. Preda, S. Zorzi, E. Verri, F. Nole’, B. A. Jereczek-Fossa
Medical Oncology.2017;[Epub] CrossRef
Clinical study on collagen gel droplet-embedded culture drug sensitivity test for multidrug combination chemotherapy and super selective intra-arterial infusion chemoradiotherapy in oral squamous cell carcinoma
Kaname Sakuma, Ryuki Tamura, Shintaro Hanyu, Haruka Takahashi, Hideaki Sato, Takahiro Oneyama, Akira Yamaguchi, Akira Tanaka
Molecular and Clinical Oncology.2017;[Epub] CrossRef
Significance of mammalian target of rapamycin in patients with locally advanced stage IV head and neck squamous cell carcinoma receiving induction chemotherapy with docetaxel, cisplatin, and fluorouracil
Shau‐Hsuan Li, Wei‐Che Lin, Tai‐Lin Huang, Chang‐Han Chen, Tai‐Jan Chiu, Fu‐Min Fang, Wan‐Ting Huang, Cheng‐Ming Hsu, Sheng‐Dean Luo, Chi‐Chih Lai, Yan‐Ye Su, Hui‐Ching Chuang, Chih‐Yen Chien
Head & Neck.2016;[Epub] CrossRef
Betel nut chewing history is an independent prognosticator for smoking patients with locally advanced stage IV head and neck squamous cell carcinoma receiving induction chemotherapy with docetaxel, cisplatin, and fluorouracil
Yan-Ye Su, Chih-Yen Chien, Sheng-Dean Luo, Tai-Lin Huang, Wei-Che Lin, Fu-Min Fang, Tai-Jan Chiu, Yen-Hao Chen, Chi-Chih Lai, Cheng-Ming Hsu, Shau-Hsuan Li
World Journal of Surgical Oncology.2016;[Epub] CrossRef
Docetaxel, cisplatin, and fluorouracil for patients with inoperable recurrent or metastatic head and neck squamous cell carcinoma
Hironori Cho, Suetaka Nishiike, Yoshifumi Yamamoto, Yukinori Takenaka, Susumu Nakahara, Toshimichi Yasui, Atsushi Hanamoto, Hidenori Inohara
Auris Nasus Larynx.2015; 42(5): 396. CrossRef
Multicenter phase II study of weekly docetaxel, cisplatin, and S-1 (TPS) induction chemotherapy for locally advanced squamous cell cancer of the head and neck
Woo Kyun Bae, Jun Eul Hwang, Hyun Jeong Shim, Sang Hee Cho, Ki Hyeong Lee, Hye Suk Han, Eun-Kee Song, Hwan Jung Yun, In Sung Cho, Joon Kyoo Lee, Sang-Chul Lim, Woong-Ki Chung, Ik-Joo Chung
BMC Cancer.2013;[Epub] CrossRef
Adjuvant Postoperative Radiotherapy with or without Chemotherapy for Locally Advanced Squamous Cell Carcinoma of the Head and Neck: The Importance of Patient Selection for the Postoperative Chemoradiotherapy
Jong Hoon Lee, Jin Ho Song, Sang Nam Lee, Jin Hyoung Kang, Min Sik Kim, Dong Il Sun, Yeon-Sil Kim
Cancer Research and Treatment.2013; 45(1): 31. CrossRef
A case involving long-term survival after esophageal cancer with liver and lung metastases treated by multidisciplinary therapy: report of a case
Daisuke Iitaka, Atsushi Shiozaki, Hitoshi Fujiwara, Daisuke Ichikawa, Kazuma Okamoto, Shuhei Komatsu, Yasutoshi Murayama, Hisashi Ikoma, Yoshiaki Kuriu, Masayoshi Nakanishi, Toshiya Ochiai, Yukihito Kokuba, Teruhisa Sonoyama, Eigo Otsuji
Surgery Today.2013; 43(5): 556. CrossRef
Usefulness and Indication of Superselective Intra-arterial Chemotherapy via the Radial Artery for Advanced Head and Neck Cancer^|^mdash;a Indication for Inaccessible to Treatment with Seldingers Method^|^mdash;
Junkichi Yokoyama, Shin Ito, Shinichi Ohba, Mitsuhisa Fujimaki, Katsuhisa Ikeda, Makoto Hanaguri
Nippon Jibiinkoka Gakkai Kaiho.2012; 115(6): 625. CrossRef
Examination on the Effect of Docetaxel Dilution Concentration on the Hypersensitivity Revelation Rate
Tatsuya Hayama, Masatoshi Hayasaka, Mei Onuma, Toshimitsu Nakayama, Sadao Amano, Yoshikazu Yoshida
Iryo Yakugaku (Japanese Journal of Pharmaceutical Health Care and Sciences).2012; 38(9): 547. CrossRef
Chemotherapy with Modified Docetaxel, Cisplatin, and 5-Fluorouracil in Patients with Metastatic Head and Neck Cancer
Jen-Tsun Lin, Guam-Min Lai, Tung-Hao Chang, Mu-Tai Liu, Chu-Ping Bi, Jer-Wei Wang, Mu-Kuan Chen
Advances in Therapy.2012; 29(1): 71. CrossRef
Heterogeneity of anticancer drug sensitivity in squamous cell carcinoma of the tongue
Minako Suzuki, Hiroshi Ishikawa, Akira Tanaka, Izumi Mataga
Human Cell.2011; 24(1): 21. CrossRef

11,455 View
66 Download
17 Crossref

First
Prev
Page of 1
Next
Last

Search