Exploratory Study on the Relationship Between FcγRIIIa Gene Polymorphisms and the Efficacy and Toxicity of Rituximab in the Treatment of Stage I/II Diffuse Large B-Cell Lymphoma

2019 ◽  
Vol 9 (5) ◽  
pp. 615-622
Author(s):  
Zhijun Wuxiao ◽  
Hua Wang ◽  
Qunhao Su ◽  
Haiyan Zhou ◽  
Min Hu ◽  
...  
Keyword(s):  
B Cell ◽  
Gene Polymorphisms ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Stage I ◽  
Term Survival ◽  
Large B Cell Lymphoma ◽  
Significant Difference ◽  
The Relationship ◽  
Large B Cell

Rituximab is an IgG1 monoclonal antibody approved for the treatment of diffuse large B-cell lymphoma (DLBCL); however, its efficacy is poor in some patients. Previous studies indicate that the difference in efficacy may be due to antibody-dependent cell-mediated cytotoxicity (ADCC). The effect of ADCC is closely related to Fcγ receptor IIIA (FcγRIIIa) receptor gene polymorphisms, but no study has investigated this gene in patients with DLBCL in China. In this study, we explored FcγRIIIa gene polymorphisms in patients with DLBCL in China and the ethnic differences in the FcγRIIIa gene. Moreover, we determined the relationship between FcγRIIIa gene polymorphisms and the effect and toxicity of rituximab treatment. Peripheral blood samples of 60 patients with newly diagnosed stage I/II DLBCL who received standard treatment with rituximab were collected, and DNA samples were extracted and normalized. Among the FcγRIIIa gene polymorphisms, there was a homozygous mutation, a heterozygous mutation, and a wild-type genotype at the site of 161514542 (rs396991). The proportion of these genotypes was significantly different from those found in previous studies for European and American populations and healthy Chinese populations. Moreover, we found that individuals with the homozygous (158-V/V) or heterozygous (V/F) mutation possessed better near-term effectiveness of the standard chemotherapeutic treatment, although there was no significant difference in long-term survival. However, patients with one of these genotypes usually suffer from a more severe hematological toxicity in response to the rituximab treatment. In conclusion, knowledge of a patient's FcγRIIIa gene polymorphism may be of value for the individualized treatment of DLBCL, which is worthy of follow-up research.

scholarly journals Long-Term Survival and Gradual Recovery of B Cells in Patients (Pts) with Refractory Large B Cell Lymphoma (LBCL) Treated with Axicabtagene Ciloleucel (Axi-Cel)

2021 ◽  
Vol 27 (3) ◽  
pp. S404-S405
Author(s):  
Caron A. Jacobson ◽  
Frederick L. Locke ◽  
Armin Ghobadi ◽  
David B. Miklos ◽  
Lazaros J. Lekakis ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Term Survival ◽  
Long Term Survival ◽  
Large B Cell Lymphoma ◽  
Large B Cell

scholarly journals Bone Marrow Molecular Markers Associated with Relapsed/Refractory Activated B-Cell-Like Diffuse Large B-Cell Lymphoma

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Di Wang ◽  
Peng Liu ◽  
Yue Zhang ◽  
Hui-Ying Liu ◽  
Di Shen ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Molecular Markers ◽  
B Cell ◽  
Bone Marrow Aspirate ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Significant Finding ◽  
Large B Cell Lymphoma ◽  
Significant Difference ◽  
Large B Cell

Activated B-cell-like diffuse large B-cell lymphoma (ABC-DLBCL) is a common subtype of non-Hodgkin’s lymphoma and is very likely to infiltrate the bone marrow. Over 30% of patients are converted to relapsed/refractory DLBCL after first-line rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisone therapy, with a poor prognosis. Our aim was to identify molecular markers that might be utilized to predict relapsed/refractory ABC-DLBCL patients. Hence, we collected bone marrow aspirate smears from 202 patients with ABC-DLBCL and detected expression of bone marrow molecular marker proteins by immunocytochemistry. Signal transducer and activator of transcription (Stat)3, nuclear factor (NF)-κB p65, Syk, Bruton’s tyrosine kinase (BTK), and Bcl2 proteins were strongly expressed in bone marrow aspirate smears of ABC-DLBCL patients. The same smear could present positive expression of multiple proteins simultaneously. Positive combinations of protein expression were associated with resistance. The most significant finding was that the Stat3+NF-κB+ group developed resistance, which was significantly higher than that of the Stat3-NF-κB-group (80 vs. 14%). There was a significant difference in two-year relapse-free survival between protein-positive and protein-negative combinations of Stat3-NF-κB (P = 0.005), Bcl2-Stat3 (P = 0.009), Bcl2-Pax5 (P = 0.003), and BTK-Syk (P < 0.001). Thus, we detected key molecules in multiple signaling pathways in bone marrow aspirate smears. At the same time, the results provide further clinical evidence of ABC-DLBCL drug-resistant molecules and provide a theoretical basis for rational second-line treatment after drug resistance.

Outcome of Diffuse Large B-Cell Lymphoma with First-line Chemotherapy

2021 ◽  
Vol 5 (01) ◽  
pp. 03-09
Author(s):  
Zulfia Zinat Chowdhury ◽  
Tamanna Bahar ◽  
Shaila Rahman ◽  
Salina Haque ◽  
A K M Mynul Islam ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
First Line ◽  
Non Hodgkin Lymphoma ◽  
Large B Cell Lymphoma ◽  
Retrospective Data Analysis ◽  
Significant Difference ◽  
Line Chemotherapy ◽  
Large B Cell

Background: Diffuse Large B-Cell Lymphoma (DLBCL), most common Non-Hodgkin Lymphoma (NHL) variety, is an aggressive, fast-growing form comprising up to 40% of all cases globally. Objective: To observe the treatment outcome of different subtypes of Diffuse Large B-Cell Lymphoma (DLBCL) after first-line chemotherapy and also the association with IHC, presenting age, sex, and IPI score with outcome. Methodology: This is a retrospective data analysis included all DLBCL patients registered in the department of Haematology of National Institute of Cancer Research and Hospital (NICRH) between July 2016 to June 2019. Results: Total 188 cases were included in this study and mean age was 48 years with a Standard deviation of 15 years with Male (69.1%) predominance. We divide the cases into three different entities of DLBCL [Germinal Centre B-cell like (GCB), Non-GCB and others (NOS) among them Non-GCB variety was the prevalent (47.3%) one. After first line   chemotherapy 52.1% complete remission with 7% death was observed in overall outcome. There was no significant difference in outcome among different types of DLBCL after chemotherapy based on Han’s algorithm. Rituximab with CHOP has significantly better outcome than CHOP alone arm (p: 0.021). Conclusion: This limited database study of NICRH will help to ascertain the outcome of DLBCL after first-line chemotherapy in Bangladesh.

scholarly journals Interaction between BCL2 and Interleukin-10 Gene Polymorphisms Alter Outcomes of Diffuse Large B-Cell Lymphoma following Rituximab Plus CHOP Chemotherapy

2009 ◽  
Vol 15 (6) ◽  
pp. 2107-2115 ◽  
Author(s):  
Yeon Hee Park ◽  
Sang Kyun Sohn ◽  
Jong Gwang Kim ◽  
Myung-Hoon Lee ◽  
Hong Suk Song ◽  
...  
Keyword(s):  
B Cell ◽  
Gene Polymorphisms ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Interleukin 10 ◽  
Chop Chemotherapy ◽  
Large B Cell Lymphoma ◽  
Large B Cell

scholarly journals A multi-institutional and case-matched control study on treatment outcomes of consolidative radiotherapy after a full course of R-CHOP compared with R-CHOP alone in Stage I–II diffuse large B-cell lymphoma (KROG 17-02)

2019 ◽  
Vol 60 (5) ◽  
pp. 677-684
Author(s):  
Mi Joo Chung ◽  
Won Kyung Cho ◽  
Dongryul Oh ◽  
Keun-Yong Eom ◽  
Jin Hee Kim ◽  
...  
Keyword(s):  
B Cell ◽  
Treatment Outcomes ◽  
Tumor Size ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Stage I ◽  
Chop Chemotherapy ◽  
Bulky Disease ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract We compared treatment outcomes between rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy alone with R-CHOP followed by consolidative radiation therapy (RT) in diffuse large B-cell lymphoma (DLBCL). We analyzed 404 patients with Stage I–II DLBCL who received six to eight cycles of R-CHOP and achieved a good response after a full course of chemotherapy. Propensity-score matching was used to assess the role of consolidative RT. The R-CHOP alone group (n = 184) was matched in a 1:2 ratio with the R-CHOP plus RT group (n = 92). Twenty-four (13.0%) of 184 patients receiving R-CHOP alone and 8 (8.7%) of 92 patients receiving R-CHOP plus RT had bulky diseases (>7.5 cm). A Deauville score of 1–2 was achieved for 159 (86.4%) of 184 patients receiving R-CHOP alone and 84 (91.3%) of 92 patients receiving R-CHOP plus RT. After a median follow-up time of 42 months, the recurrence-free survival (RFS) rate (86.7% vs 93.0%, P = 0.464) and overall survival rate (88.3% vs 95.1%, P = 0.295) at 5 years did not differ significantly between the R-CHOP alone and R-CHOP plus RT arms. In the additional multivariate analyses, large tumor size (>7.5 cm) was significantly associated with decreased RFS (hazard ratio, 2.368 and confidence interval, 1.837–6.697; P = 0.048). Consolidative radiation was not a significant factor for RFS (P = 0.563). Tumor size was a significant factor for RFS in the rituximab era. The outcome of omitting consolidative RT for good responders after six to eight cycles of R-CHOP chemotherapy was acceptable in early-stage DLBCL without a bulky disease.

scholarly journals International prognostic indices in diffuse large B-cell lymphoma: a comparison of IPI, R-IPI, and NCCN-IPI

Blood ◽  
2020 ◽  
Vol 135 (23) ◽  
pp. 2041-2048 ◽  
Author(s):  
Amy S. Ruppert ◽  
Jesse G. Dixon ◽  
Gilles Salles ◽  
Anna Wall ◽  
David Cunningham ◽  
...  
Keyword(s):  
B Cell ◽  
Randomized Clinical Trials ◽  
Cell Lymphoma ◽  
International Prognostic Index ◽  
B Cell Lymphoma ◽  
Absolute Difference ◽  
Term Survival ◽  
Large B Cell Lymphoma ◽  
Risk Categories ◽  
Large B Cell

Abstract Great heterogeneity in survival exists for patients newly diagnosed with diffuse large B-cell lymphoma (DLBCL). Three scoring systems incorporating simple clinical parameters (age, lactate dehydrogenase, number/sites of involvement, stage, performance status) are widely used: the International Prognostic Index (IPI), revised IPI (R-IPI), and National Comprehensive Cancer Network IPI (NCCN-IPI). We evaluated 2124 DLBCL patients treated from 1998 to 2009 with frontline rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP; or variant) across 7 multicenter randomized clinical trials to determine which scoring system best discriminates overall survival (OS). Median age was 63 years, and 56% of patients were male. Five-year OS estimates ranged from 54% to 88%, from 61% to 93%, and from 49% to 92% using the IPI, R-IPI, and NCCN-IPI, respectively. The NCCN-IPI had the greatest absolute difference in OS estimates between the highest- and lowest-risk groups and best discriminated OS (concordance index = 0.632 vs 0.626 [IPI] vs 0.590 [R-IPI]). For each given IPI risk category, NCCN-IPI risk categories were significantly associated with OS (P ≤ .01); the reverse was not true, and the IPI did not provide additional significant prognostic information within all NCCN-IPI risk categories. Collectively, the NCCN-IPI outperformed the IPI and R-IPI. Patients with low-risk NCCN-IPI had favorable survival outcomes with little room for further improvement. In the rituximab era, none of the clinical risk scores identified a patient subgroup with long-term survival clearly &lt;50%. Integrating molecular features of the tumor and microenvironment into the NCCN-IPI or IPI might better characterize a high-risk group for which novel treatment approaches are most needed.

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