Cancer Research and Treatment

Original Articles

Hematologic malignancy

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

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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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Hypogammaglobulinemia at Diagnosis is Associated With Inferior Survival and Higher Risk of Infections in Diffuse Large B Cell Lymphoma
Åsa Lindberg, Åsa Johansson, Fredrik Kahn, Göran Jönsson, Mats Jerkeman
Hematological Oncology.2025;[Epub] CrossRef
Predictive Model for Occurrence of Febrile Neutropenia after Chemotherapy in Patients with Diffuse Large B-Cell Lymphoma: A Multicenter, Retrospective, Observational Study
Masaya Morimoto, Yuma Yokoya, Kikuaki Yoshida, Hideki Kosako, Yoshikazu Hori, Toshiki Mushino, Shinobu Tamura, Reiko Ito, Ryosuke Koyamada, Takuya Yamashita, Shinichiro Mori, Nobuyoshi Mori, Sachiko Ohde
Hematology Reports.2024; 16(1): 76. CrossRef
Multi‐omics integration reveals the oncogenic role of eccDNAs in diffuse large B‐cell lymphoma through STING signalling
Zijuan Wu, Wei Zhang, Luqiao Wang, Jiayan Leng, Yongle Li, Zhou Fan, Mengtao Zhan, Lei Cao, Yongning Jiang, Yan Jiang, Bing Sun, Jianxin Fu, Jianyong Li, Wenyu Shi, Hui Jin
Clinical and Translational Medicine.2024;[Epub] CrossRef
Transcriptomic analysis of neutrophil apoptosis induced by diffuse large B-cell lymphoma unveils a potential role in neutropenia
Byeol-Eun Jeon, Ji-Eun Lee, Jungwook Park, Hyejung Jung, Eun Gyung Park, Du Hyeong Lee, Young-Su Seo, Heui-Soo Kim, Ho-Jin Shin, Sang-Woo Kim
Genes & Genomics.2023; 45(8): 1013. CrossRef

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Pegfilgrastim Prophylaxis Is Effective in the Prevention of Febrile Neutropenia and Reduces Mortality in Patients Aged ≥ 75 Years with Diffuse Large B-Cell Lymphoma Treated with R-CHOP: A Prospective Cohort Study: Seong Hyun Jeong, Seok Jin Kim, Dok Hyun Yoon, Yong Park, Hye Jin Kang, Youngil Koh, Gyeong-Won Lee, Won-Sik Lee, Deok-Hwan Yang, Young Rok Do, Min Kyoung Kim, Kwai Han Yoo, Yoon Seok Choi, Hwan Jung Yun, Jun Ho Yi, Jae-Cheol Jo, Hyeon-Seok Eom, Jae-Yong Kwak, Ho-Jin Shin, Byeong Bae Park, Shin Young Hyun, Seong Yoon Yi, Ji-Hyun Kwon, Sung Yong Oh, Hyo Jung Kim, Byeong Seok Sohn, Jong Ho Won, Se-Hyung Kim, Ho-Sup Lee, Cheolwon Suh, Won Seog Kim; Cancer Res Treat. 2022;54(4):1268-1277. Published online December 30, 2021; DOI: https://doi.org/10.4143/crt.2021.1168

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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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Sarcopenia attenuates the efficacy of PEGylated granulocyte colony-stimulating factor in preventing febrile neutropenia
Se-Il Go, Eun-Jeong Jeong, Woo Je Lee, Sungwoo Park, Mi Jung Park, Gyeong-Won Lee
Supportive Care in Cancer.2025;[Epub] CrossRef

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A Phase II Study to Evaluate the Safety and Efficacy of Pegteograstim in Korean Breast Cancer Patients Receiving Dose-Dense Doxorubicin/Cyclophosphamide: Gun Min Kim, Joo Hoon Kim, Ji Heung Kim, Young Up Cho, Seung Il Kim, Seho Park, Hyung Seok Park, Ji Ye Kim, Joohyuk Sohn; Cancer Res Treat. 2019;51(2):812-818. Published online September 19, 2018; DOI: https://doi.org/10.4143/crt.2018.383

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Purpose
Dose-dense chemotherapy (DD-CT) is a preferred (neo)adjuvant regimen in early breast cancer (BC). Although the results of reported randomized trials are conflicting, a recent metaanalysis showed improved overall and disease-free survival with DD-CT compared to conventional schedules. However, no DD-CT safety data for Korean BC patients are available. This phase II study was conducted to evaluate the safety and efficacy of pegteograstim in Korean BC patients receiving DD-CT.
Materials and Methods
Patients with operable (stage I-III), histologically confirmed BC received four cycles of intravenous doxorubicin (60 mg/m2) and cyclophosphamide (600 mg/m2) on day 1 every 2 weeks as neoadjuvant or adjuvant therapy. Pegteograstim (6.0 mg) was administered subcutaneously on day 2 of each cycle. The primary endpoint was the incidence of febrile neutropenia (FN). The secondary endpoints were safety and tolerability.
Results
Of 63 patients, one (1.6%) developed FN during all cycles of DD-CT. Dose delay was observed in four patients (6.3%) and dose reduction in two (3.2%) during DD-CT. Frequent adverse events (AEs) were nausea, alopecia, generalized muscle weakness, myalgia, mucositis, anorexia, dyspepsia, and diarrhea; most AEs were related to chemotherapy. Grade 3-4 AEs were reported in five of 63 patients (7.9%), and all grade 3 and 4 AEs were related to chemotherapy. Adverse drug reactions possibly linked to pegteograstim were abdominal pain, bone pain, myalgia, generalized muscle weakness, and headache in five of 63 patients (7.9%).
Conclusion
Dose-dense AC (doxorubicin/cyclophosphamide) chemotherapywith pegteograstim support is a tolerable and safe regimen in Korean early BC patients.

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Local dose-dense chemotherapy for triple-negative breast cancer via minimally invasive implantation of 3D printed devices
Noehyun Myung, Hyun-Wook Kang
Asian Journal of Pharmaceutical Sciences.2024; 19(1): 100884. CrossRef
Safety and Efficacy of Pegteograstim on Chemotherapy-induced Neutropenia in Children and Adolescents With Solid Tumors
Hee Won Cho, Ji Won Lee, Hee Young Ju, Ju Kyung Hyun, Keon Hee Yoo, Hong Hoe Koo, Kyunga Kim, Ki Woong Sung
Journal of Pediatric Hematology/Oncology.2022; 44(2): e362. CrossRef
Prophylaxis and treatment strategies for optimizing chemotherapy relative dose intensity
Michelle Shayne, R. Donald Harvey, Gary H. Lyman
Expert Review of Anticancer Therapy.2021; 21(10): 1145. CrossRef

8,501 View
268 Download
4 Web of Science
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