Cancer Research and Treatment

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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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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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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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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