Cancer Research and Treatment

Original Articles

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

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

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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

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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

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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

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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

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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

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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
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Hsiang-Lan Lai, Yeh Tang, Chih-Yen Chien, Fu-Min Fang, Tai-Lin Huang, Tai-Jan Chiu, Shau-Hsuan Li
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