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Статті в журналах з теми "Gcb-Dlbcl":
1
Pukiat, Sulada, Nuttapong Ngamphaiboon, Pooja Advani, Julio Chavez, George Deeb, Anjana Elefante, and Francisco J. Hernandez-Ilizaliturri. "BCL-2 Expression at the Time of Diagnosis Affects the Clinical Outcome of Patients with Germinal Center and Non-Germinal Center Diffuse Large B-Cell Lymphoma (DLBCL) Treated with Chemo-Immunotherpy." Blood 116, no. 21 (November 19, 2010): 3130. http://dx.doi.org/10.1182/blood.v116.21.3130.3130.
Анотація:
Abstract Abstract 3130 DLBCL has been recognized as a heterogeneous disease varying in molecular biology and clinical outcome. The use of genetic expression profiling has led to the sub-classification of DLBCL into germinal center B-cell like (GCB) and non-germinal center B cell like (non-GCB) based on the cell of origin of the neoplastic B-cell. Immunohistochemistry (IHC) algorithms had been developed and validated to identify GCB or non-GCB DLBCL. Deregulation of Bcl-2 family member of proteins plays an important role in the development, progression, and prognosis of various subtypes of B-cell neoplasms, including DLBCL. Bcl-2 protein expression is a previously known negative prognostic indicator of clinical outcome in DLBCL treated with antracycline-containing combination chemotherapy (e.g. CHOP) in the past. In the post-rituximab (R) era (e.g. use of upfront R-CHOP), the negative prognostic value of Bcl-2 protein expression needs to be reevaluated to ensure its validity. To study the prognostic value of Bcl-2 in patients with either GCB or non-GCB DLBCL, we retrospectively analyzed differences in progression-free survival (PFS) and overall survival (OS) between Bcl-2+ and Bcl-2- de novo DLBCL (GCB or non-GCB subtypes). Using the RPCI tumor registry and pharmacy database, we identified 201 DLBCL patients treated with equivalent doses of rituximab and anthracycline-based therapy (i.e. R=CHOP or R+DA-EPOCH) at RPCI between 1997 and 2007. Demographic, clinical and pathological characteristics were obtained for each patient. Patients were classified into GCB or non-GCB DLBCL according to the Han's algorithm based on the expression of CD10, Bcl-6 and MUM-1. Bcl-2 was determined by IHC and was available for 101 patients. Using the Han's algorithm, fifty-three patients (26.4%) were classified as GCB, 54 patients (26.9%) non-GCB, and 94 patients (46.8%) could not be classified due to inadequate data/sample. Bcl-2 expression was detected in 67% and 73% of the GCB- and non-GCB DLBCL subtypes respectively. Demographics and clinical characteristics were equally distributed between GCB- and non-GCB DLBCL. Patients received either R+CHOP (90%) or R+DA-EPOCH (10%). The complete response (CR) rate of the entire cohort was 82.6% and no differences were observed between GCB- or non-GCB DLBCL (78.4% vs. 75.5%, P=0.73) or by Bcl-2 expression (+:72.5% vs. -:81.3%, P=0.35]. After a median follow up period of 74 months, significant differences were observed between Bcl-2 positive or negative and GCB or non-GCB DLBCL. GCB-DLBCL had a longer 5-yr PFS and 5-yr OS than non-GCB DLBCL (58.5% vs. 37%, P=0.026; 81.1% vs. 53.7% and, P=0.002; respectively). By itself, Bcl2 over-expression, had a negative impact in PFS (P=0.002) and OS (P=0.001) in R+CHOP/R+DA-EPOCH treated de novo DLBCL. The combined prognostic value of the Han's algorithm and Bcl-2 expression was also evaluated. Bcl-2 expression in the context of both GBC and non-GCB subtypes remains an unfavorable prognostic indicator for overall survival, with a more pronounced influence in the GCB-DLBCL phenotype (See table). Our data supports the predictive value of the Han's algorithm and Bcl-2 expression in DLBCL patients undergoing front-line chemo-immunotherapy. Bcl-2 expression is associated with a poor prognosis in GCB and non-GCB DLBCL. It is possible that intrinsic biological pathways involved in lymphomagenesis and/or “resistance” of these subtypes of DLBCL may play a role in their responsiveness to rituximab-based therapies and could be influenced by the net balance between pro- and anti-apoptotic proteins. Attempts to further delineate the biological heterogeneity of DLBCL may help identify subgroups of patients at high risk of resistance to chemo-immunotherapy and lead to the development of new therapeutic strategies. In conclusion, our data analysis confirms that the DLBCL immunophenotypes based on cell of origin and Bcl-2 status continues to have predictive significance on clinical outcomes in DLBCL in the rituximab era. Differences in clinical outcomes between GCB or non-GCB-DLBCL by Bcl-2 status Median PFS (months) Significance Median OS (months) Significance GCB-DLBCL Bcl-2 (-) NR *P = 0.016 NR *P =0.029 Bcl-2 (+) 39 83 Non-GCB DLBCL Bcl-2 (-) 49.8 NR Bcl-2 (+) 15 48 PFS = Progression free survival, OS = overall survival, GCB = germinal center B-cell, DLBCL = diffuse large B-cell lymphoma. * P values calculated by comparing GCB-DLBCL Bcl-2 (-) to the other groups Disclosures: No relevant conflicts of interest to declare.
2
Tarius, Jenifer Marsela, Hermawan Istiadi, Ika Pawitra Miranti, and Intan Rahmania Eka Dini. "THE CORRELATION BETWEEN CELL OF ORIGIN SUBTYPE WITH OVERALL SURVIVAL OF DIFFUSE LARGE B-CELL LYMPHOMA PATIENTS IN KARIADI GENERAL HOSPITAL SEMARANG." DIPONEGORO MEDICAL JOURNAL (JURNAL KEDOKTERAN DIPONEGORO) 9, no. 3 (May 12, 2020): 252–58. http://dx.doi.org/10.14710/dmj.v9i3.27504.
Анотація:
Background: DLBCL is the most common type of NHL in the world. DLBCL based on cell of origin is divided into GCB and non-GCB. The diagnosis of DLBCL has not been routinely done to its cell of origin, and there have not been many studies that discuss the DLBCL subtype and the overall survival of the patients, especially in Kariadi General Hospital. This study aims to determine the correlation of DLBCL cell of origin with the 2-year overall survival of DLBCL patients in Kariadi General Hospital. Methods: This is an observational analytic study of 40 DLBCL patients in Kariadi General Hospital from January to August 2017. The data collection including: age of diagnosis, location, stage and 2-year overall survival. Data analysis used chi square test and Kaplan Meier curve. Results: GCB patients had higher 2-year overall survival than non-GCB subtype significantly (p: 0.047), with a 2-year survival rate of GCB subtype was 66.7% and non-GCB subtype was 31.6%. GCB patients tend to have early stage than non-GCB subtype significantly (p:0.028). Conclusion: DLBCL GCB subtype patients had significantly higher 2-year overall survival therefore it has better prognosis than non-GCB subtype.
3
Gandhi, Shipra, Vishala T. Neppalli, George Deeb, Myron S. Czuczman, and Francisco J. Hernandez-Ilizaliturri. "Distinct CD30 Expression Patterns In Germinal Center B-Cell (GCB) and Non-GCB Diffuse Large B-Cell Lymphoma (DLBCL)." Blood 122, no. 21 (November 15, 2013): 5064. http://dx.doi.org/10.1182/blood.v122.21.5064.5064.
Анотація:
Abstract Background DLBCL is the most common type of non-Hodgkin lymphoma, which demonstrates morphologic, immunophenotypic, molecular, and clinical heterogeneity. Gene expression profiling studies define two molecular subtypes of DLBCL, namely germinal center B-cell-like (GCB) and activated B-cell-like (ABC) DLBCL. Hans' algorithm was developed to provide an immunohistochemical correlation to the molecular subtypes of DLBCL. In the pre and post-rituximab era, ABC subtype of DLBCL is known to demonstrate poor overall survival when compared to GCB subtype. In addition, relapsed or primary refractory DLBCL responds poorly to current therapeutic strategies. These findings underscore the necessity to identify novel therapeutic targets in DLBCL to achieve better clinical outcomes. Recent data suggests that CD30, a member of the tumor necrosis factor receptor family, is a potential therapeutic target in DLBCL. CD30 is widely expressed in classical Hodgkin lymphoma (cHL) and anaplastic large cell lymphoma (ALCL) thus serving as an attractive target of immunotherapy for cHL and ALCL. In this study we conducted a retrospective evaluation of CD30 expression in GCB and non-GCB DLBCL, treated at our Institution with standard front-line chemo-immunotherapy (i.e. R+CHOP or R+ DA-EPOCH). Materials and Methods We identified 60 patients with confirmed DLBCL for which archived formalin fixed paraffin embedded tissue was available in the form of a tissue micro-array (39 Cases) or diagnostic biopsy material (21 Cases). Immunohistochemical detection of CD30 was performed using routine methods (Biocare #PM031, ready to use aliquots). Demographic, clinical and pharmacological parameters were obtained for each patient. DLBCL cases were subtyped as GCB or non-GCB using immunohistochemistry-based Hans' algorithm. Membranous and Golgi pattern of CD30 expression in the tumor cells was designated as positive. Results 21 patients (48.8%) were classified as GCB, 22 patients (51.2%) non-GCB. CD30 expression was detected in 13.3% of all DLBCL patients. Differences in CD30 expression were noted between GCB- and non-GCB DLBCL. CD30 expression was detected in 9.5% and 23% of the GCB- and non-GCB DLBCL subtypes respectively. Demographics and clinical characteristics were equally distributed between GCB- and non-GCB and between CD30 positive or negative DLBCL. Patients received either R+CHOP (82%) or R+DA-EPOCH (18%). The complete response (CR) rate of the entire cohort was 67% and no differences were observed between GCB- or non-GCB DLBCL. CD30 (+) DLBCL had a higher CR (complete response) rate than CD30 (-) DLBCL (88% vs 63.4%). However, the numbers were too small to reach statistical significance. No significant differences were observed between CD30 (+) or (-) DLBCL in terms of progression free survival (PFS) (CD30[-]37m vs. CD30[+]16.5m, P =0.785) or overall survival (OS) (CD30[-]86m vs. CD30[+]57.4m, P =0.99). In contrast to previously reported by other investigators, there was no difference in the clinical outcome between GCB vs. non-GCB DLBCL treated with R+CHOP or R+DA-EPOCH. Conclusions Our data suggests that CD30 expression is more prevalent in non-GCB DLBCL patients based on our small cohort. While CD30 expression may not confer a prognostic value in newly diagnosed DLBCL (Table 1), routine testing for it may identify a group of patients that may benefit from CD30-targeted therapeutic strategies (i.e. antibody-drug conjugates) in the relapsed/refractory setting. (Research, in part, supported by The Eugene and Connie Corasanti Lymphoma Research Fund) Disclosures: Czuczman: Genetech, Onyx, Celgene, Astellas, Millennium, Mundipharma: Advisory Committees Other. Hernandez-Ilizaliturri:Seattle Genetics: Consultancy, Honoraria.
4
Hayama, Miyuki, Masataka Okamoto, Yuki Hagiwara, Ken Tanae, Mika Kohri, Naoki Takahashi, Tadashi Yoshino, Koichi Ohshima, and Nozomi Niitsu. "Clinical Significance of Immunohistochemical Markers of Diffuse Large B-Cell Lymphoma In the Rituximab Era." Blood 116, no. 21 (November 19, 2010): 1800. http://dx.doi.org/10.1182/blood.v116.21.1800.1800.
Анотація:
Abstract Abstract 1800 Rituximab combination chemotherapy has significantly improved the treatment outcome of diffuse large B-cell lymphoma (DLBCL). Therefore, the prognostic factors of DLBCL in the rituximab era are different from previously reported prognostic factors. Biological prognostic markers have been analyzed to help understand the biologic basis of treatment outcome. Hans, et al. reported that patients with non-germinal center B-cell like (GCB)-type DLBCL had a significantly poorer prognosis than those with GCB-type DLBCL in the pre-rituximab era. In patients who received rituximab combination chemotherapy, there is a report that did not find a difference in survival ratio between those with GCB DLBCL or non-GCB DLBCL. On the other hand, there was a report that found a difference in survival ratio between patients with GCB DLBCL and those with non-GCB DLBCL. In the present study, we compared the prognostic factors of DLBCL between patients who received CHOP-like chemotherapy and those who received rituximab combined with CHOP-like therapy. The subjects were 204 DLBCL patients who underwent rituximab + CHOP-like therapy and in whom markers could be analyzed. We evaluated CD5, CD10, BCL2, BCL6, and MUM1 expression by immunohistochemistry. One hundred forty-six DLBCL patients who underwent CHOP-like therapy were assumed as historical controls. The median age was 52 years in both groups. In the R-CHOP-like and CHOP-like groups, patients with stage III or IV disease comprised 75% and 67%, respectively, patients with performance status3a2 comprised 28% and 20%, respectively, and patients with serum LDH >normal comprised 60% and 77%, respectively. There were no significant differences in clinical characteristics between the CHOP-like group and R-CHOP-like group. BCL2 was positive in 85(63%) of the 134 patients who received the R-CHOP-like regimen and in 66 (46%) of the 142 patients who received the CHOP-like regimen. When the 202 patients who received the R-CHOP-like regimen were divided into the GCB group and the non-GCB group, the GCB group consisted of 92 patients (46%) and the non-GCB group consisted of 110 patients. The relationships between immunohistological markers and outcome among the patients with DLBCL who received CHOP-like therapy were studied. CD5, CD10, and BCL6 had no prognostic impact on 5-year overall survival (OS) and progression-free survival (PFS) rates. When the patients were divided into the GCB DLBCL and non-GCB DLBCL groups, the 5-year OS of the GCB group was 78% and that of the non-GCB group was 57% (p<0.05). The 5-year PFS of the GCB group was 73% and that of the non-GCB group was 52% (p<0.05). The 5-year OS rate of the BCL2-positive and -negative groups was 61% and 74%, respectively (p<0.05). The 5-year PFS rate of the BCL2-positive and -negative groups was 55% and 70%, respectively (p<0.05). Thus, among patients who received the CHOP-like regimen, the BCL2-positive group showed significantly poorer prognosis than the BCL2-negative group. Next, the effect of rituximab with chemotherapy was examined. CD5, CD10, BCL2, BCL6, and MUM-1 had no prognostic impact on 5-year OS and PFS rates. When the patients were divided into the GCB DLBCL (n=92) and non-GCB DLBCL (n=110) groups, the 5-year OS of the GCB group was 74% and that of the non-GCB group was 75%, showing no significant difference. The 5-year PFS of the GCB group was 71% and the 5-year PFS of the non-GCB group was 69%, showing no significant difference. In the rituximab era, BCL2, MUM1 and non-GCB were not prognostic factors. As to reports on patients with DLBCL who received rituximab combination chemotherapy, there was a report in which the cases were separated into the GCB-type DLBCL and non-GCB-type DLBCL groups and compared. Fu, et al. reported that the survival of patients with GCB-type DLBCL was still superior to that of patients with non-GCB-type DLBCL in the rituximab era. However, other reports did not find a difference in survival ratio between those with GCB-type DLBCL or non-GCB-type DLBCL. In conclusion, the finding of improved OS and PFS with the addition of rituximab indicates that new biomarkers should be studied. Disclosures: No relevant conflicts of interest to declare.
5
Kharchenko, Yevgeniya, Tatyana Semiglazova, Anna Artemeva, Galina Kireeva, I. Polyatskin, Ilya Zyuzgin, Larisa Filatova, Yuliya Chudinovskikh, Margarita Motalkina, and Yuliya Oleynik. "PROGNOSTIC IMPACT OF IMMUNOHISTOCHEMICAL AND MOLECULAR GENETIC MARKERS IN DIFFUSE LARGE B-CELL LYMPHOMA." Problems in oncology 66, no. 1 (January 1, 2020): 79–89. http://dx.doi.org/10.37469/0507-3758-2020-66-1-79-89.
Анотація:
Aim: To identify incidence and prognostic impact of different IHC and molecular genetic markers in Diffuse Large B-cell lymphoma. Methods: We analyzed 215 patients with DLBCL who received treatment from 2008 to 2016. We assess expression of different IHC markers, defined DLBCL to GCB and non-GCB subtypes by Hans-algorithm and performed FISH to evaluate MyC, BcL2 and BCL6 translocations. Results: Median follow-up was 29 months. Non-GCB DLBCL were identified in 44 pts (62,9%), GCB-subtype in 26 pts (37,1%). Median PFS in non-GCB DlBCL was 46,0 months, in GCB DLBCL median PFS and 75% quartile was not reached (p=0,171). Traslocations of MYC, BCL2 and BCL6 were found in 10/48 pts (20,8%). Double expression of c-myc and bcl-2 was identified in 21 of 71 пациентов (29,6%). СD5-expression were determined in 19/55 (34,5%), CD30+ DLBCL - in 24/66 pts (36,4%). In pts with DLBCL without CD-10 expression PFS was 6,0 months, in group with CD 10 expression median of PFS was not reached (р=0,122). Pts with CD 10 expression had lower risk of relapse compared to those without expression (р=0,049). Absence of CD 10 expression was negative prognostic factor for PFS in multivariate analysis (р=0,015). Conclusion: Patients with DLBCL and GCB subtype have tendency to better prognosis in PFS rates and lower risk of relapse compared to non-GCB subtype. Dividing to GCB or non-GCB subtypes in DLBCL and assessment of different IHC markers can potentially determine DLBCL with worse prognosis.
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Adhi Pangarsa, Eko, Desta Nur Ewika Ardini, Daniel Rizky, Kevin Tandarto, Hermawan Istiadi, Dik Puspasari, Budi Setiawan та ін. "The association of Hypoxia-Inducible Factor-2α (HIF-2α) overexpression score with Germinal Center B-Cell Like (GCB) and Non-Germinal Center B-Cell Like (Non-GCB) subtypes of Diffuse Large B-cell Lymphoma (DLBCL)". Bali Medical Journal 12, № 3 (22 серпня 2023): 2456–62. http://dx.doi.org/10.15562/bmj.v12i3.4521.
Анотація:
Link of Video Abstract: https://www.youtube.com/watch?v=KF58IGGdWmc Background: Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin's lymphoma. It is classified into homogeneous subtypes, namely Germinal Center B-Cell Like (GCB) and Non-Germinal Center B-Cell Like (GCB), with the latter associated with worse survival outcomes. Increased expression of Hypoxia-Inducible Factor-2α (HIF-2α) is often observed in DLBCL and has been correlated with enhanced angiogenesis, suggesting its potential as a prognostic factor in managing DLBCL. The study evaluates the association between HIF-2α overexpression and the GCB and non-GCB subtypes of DLBCL. Methods: This cross-sectional study utilized samples from DLBCL patients at Dr. Kariadi Semarang Hospital between January and December 2021. Immunohistochemistry was performed on the samples to determine the DLBCL subtypes and assess the presence of HIF-2α. HIF-2α was evaluated by immunohistochemistry based on its distribution and intensity. The Kruskal-Wallis test was used to find the association between HIF-2α expression and the GCB and non-GCB subtypes of DLBCL. Furthermore, Spearman's rank correlation test explored the correlation between all numeric variables. Results: A total of 30 subjects were included in this study, with 7 samples of GCB subtype (23.3%) and 23 samples of non-GCB subtype (76.6%). Kruskal-Wallis test showed no association between HIF-2α expression and the subtypes of DLBCL (p=0.812). Spearman's rho correlation test indicated no correlation between HIF-2α overexpression score with NCCN IPI score in GCB (r=0.219; p=0.637) and non-GCB (r=-0.194; p=0.386). Conclusion: There was no association between HIF-2α expression and GCB and non-GCB subtypes of DLBCL. Additionally, no correlation was found between HIF-2α overexpression and NCCN IPI score.
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Mishima, Yuko, Masahiro Yokoyama, Noriko Nishimura, Kyoko Ueda, Tadahiro Gunji, Hideaki Nitta, Yoshiharu Kusano, et al. "R-CHOP Therapy Cannot Overcome CD5 Positive Non-GCB Subtype of DLBCL." Blood 126, no. 23 (December 3, 2015): 1507. http://dx.doi.org/10.1182/blood.v126.23.1507.1507.
Анотація:
Abstract Introduction: There are various poor prognosis factors in diffuse large B cell lymphoma (DLBCL). CD5 positive (CD5+) is estimated as one of the poor prognosis markers in DLBCL. CD5+ DLBCL is completely distinguished from CLL or Mantle cell lymphoma, and de Novo CD5+ DLBCL is related to a high incidence of cytogenetic abnormalities of 8p21 and 11q13. In many cases, CD5+ DLBCL is associated with an aggressive clinical status and advanced stages. Several chromosomal studies have demonstrated the gene expression was similar to non-GCB type of DLBCL. In the clinical phase, it is easy to express chemo-resistance and CNS invasion. However, the clear characterization and mechanisms of chemo-resistance have not been demonstrated yet. In this study, we examined our previous CD5+ DLBCL patients in our institute, then evaluated the prognosis and clinical characteristics regarding GCB or non GCB type. Methods: We studied 372 newly diagnosed DLBCL patients including 42 cases of CD5+ from 2005 to 2015 in our institution retrospectively. The pathological diagnoses were performed with immunohistochemical analysis by two or three hematological pathologists. CD5 expression was evaluated by immunohistostaining and flowcytometry, then cyclin D1 positive cases were excluded. GCB or non-GCB subtype was evaluated with CD10, bcl-6, and MUM-1 of immunohistostaining. The clinical stage of patients and evaluation of the effect of the therapy were performed using PET-CT scan. The statistical analyses were performed by Dr. SPSS II. Results: In all our treated patients, 350 DLBCL patients (female;161) and 41 CD5+ patients (female 22) could be evaluated. 192 patients were GCB type and 158 patients were non-GCB type. The median age was 64.5 yrs (25-86 yrs) and the median follow up time was 45 months (1-133 months). All patients were treated by rituximab-CHOP (R-CHOP) therapy. CR rate of CD5- DLBCL was 94.2% and CD5+ was 73.1% respectively (p =0.0093). 3.5-year event free survival (EFS) was 79.16% and 52.20% (p <0.0001) and overall survival (OS) was 85.82% and 54.35 %(p <0.0001) (CD5- and CD5+ respectively). In CD5+ DLBCL, GCB type was 11 (36.6%) and non-GCB type was 30 (63.3%). In the non-GCB type of CD5+ cases, IPI low (L) and low intermediate (LI) was 86.6% (18 and 8 each) and high intermediate (HI) was 13.3% (4/30). CR of GCB type in CD5+ was 81.8% and relapse rate was 22.2% compared with CR of non-GCB in CD5+ was 70.0% and relapse rate was 52.4% respectively. All HI cases of non-GCB type could not get CR and died within 6 months. 3.5-year EFS of CD5+ DLBCL according to GCB and non-GCB were 81.82% and 40.6% (p =0.1214) and OS was 90.9% and 40.05% (p =0.0154), respectively. 3.5-year EFS of CD5- DLBCL according to GCB and non-GCB were 82.12% and 69.23% (p =0.0173), and OS of CD5- was 88.51% (GCB) and 82.12%(non-GCB) (p =0.0061) respectively. Discussion: CD5+ showed poor prognosis in our treated DLBCL, however, GCB type of CD5+ had similar OS and EFS as CD5- DLBCL. Non-GCB type of CD5+ demonstrated significantly poor prognosis compared to GCB subtype or CD5- DLBCL. The clinical status of CD5+ cases have been generally reported as having aggressive status, however, in our CD5+ of non-GCBcases, IPI L and LI were 86%. In spite of many populations of L and LI of IPI, the prognosis was poor. From these results, it suggested that it is not necessary to estimate CD5+ of GCB subtype as poor prognosis in R-CHOP therapy, however, CD5+ non-GCB type indicated independent poor prognosis factors in DLBCL. Additionally, R-CHOP therapy could induce CR at once in IPI L and LI cases, however it could not contribute to good prognoses. We should investigate other treatment strategies for improving outcomes of CD5+ non-GCB subtype of DLBCL. Disclosures Mishima: Chugai Pharmaceutical CO., LTD.: Consultancy. Yokoyama:Chugai Pharmaceutical CO., LTD.: Consultancy. Nishimura:Chugai Pharmaceutical CO., LTD.: Consultancy. Hatake:Chugai Pharmaceutical CO., LTD.: Other: lecture speaking.
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Chavez, Julio, Mark Walsh, Francisco J. Hernandez-Ilizaliturri, Anjana Elefante, and Myron S. Czuczman. "Classification of Newly Diagnosed Diffuse Large B-Cell Lymphoma (DLBCL) According to the Han's Criteria Defines Two Groups of Patients with Different Clinical Outcomes Following Systemic Rituximab-Multi Agent Anthracycline-Based Therapy." Blood 114, no. 22 (November 20, 2009): 623. http://dx.doi.org/10.1182/blood.v114.22.623.623.
Анотація:
Abstract Abstract 623 Gene expression profiling has successfully distinguished three subtypes of DLBCL with different biology and response to treatment: 1) germinal center B-cell (GCB); and 2) non-germinal center lymphomas, that include: activated B-cell-like (ABC) and Type 3 subtypes. Currently, immunohistochemical (IHC) analysis of lymphoma biopsy specimens appear to be a more widely applicable methodology (i.e. compared to gene microarray analysis) to use in order to differentiate between subtypes of DLBCL. While the clinical benefit of adding rituximab to CHOP or CHOP-like chemotherapy as a front line treatment of DLBCL is beyond dispute, it also requires a re-evaluation of previously accepted biomarkers of response to CHOP or CHOP-like chemotherapy alone. The predictive value of “IHC–defined” GCB phenotype in rituximab-chemotherapy-treated patients continues to be controversial, as retrospective studies have reported conflicting results. In an attempt to define the predictive value of using the Han's algorithm in newly diagnosed DLBCL patients undergoing frontline immunochemotherapy, we retrospectively analyzed differences in progression free survival (PFS) and overall survival (OS) between patients with GCB and non-GCB DLBCL treated with equivalent doses of rituximab and anthracycline-based therapy at our institution. Using the tumor registry and the pharmacy database, we identified patients with DLBCL treated at our Institution between 2000 and 2008. Demographic, clinical, pharmacologic and pathological characteristics were obtained for each patient. Patients were classified into GCB or non-GCB DLBCL according to the Han's algorithm based on the expression of CD10, Bcl-6 and MUM-1 in the large cell component of the tumor specimen. Cumulative doses of rituximab (R), cyclophosphamide (C), doxorubicin (H), vincristine (O), etoposide (E,; when used) and prednisone (P) were calculated for each patient, as well as the number of cycles, dose delays, and growth factor use. A total of 192 patients were included in the study. The average age was 58.65 years (F/M:73/119). Using the Hans algorithm, n=55 (28.6%) and n=57 (29.7%) were classified as non-GCB or GCB, respectively. Inadequate information was availabel to classify 80 patients (undetermined group). Clinical indictors such as clinical demographics, international prognostic index (IPI) score, extra-nodal disease, performance status, Ann Arbor stage, therapy delays, cumulative rituximab and chemotherapy doses were not significantly different between groups (non-GCB, GCB, and undetermined DLBCL). The majority of patients received R+CHOP (90%) or R+ dose adjusted–EPOCH. On follow-up, a total of 42 (21.8%) patients relapsed or were found to have primary-refractory disease. The complete remission rate to front-line therapy was 81% for the entire cohort of patients and was not different between patients with GCB or non-GCB DLBCL. On the other hand, significant differences in PFS and OS were observed between patients with non-GCB versus GCB DLBCL. The 5-year progression free survival (PFS) and overall survival (OS) were significantly better in the GCB DLBCL subtype (75.4% vs. 56.4%, p=0.017 and 84.2% vs. 70.9 %, p=0.037; respectively). As no differences in clinical parameters, CR rate, or rituximab-chemotherapy dose/schedule were observed between non-GCB and GCB DLBCL patients, it is possible that intrinsic biological pathways involved in lymphomagenesis and/or “resistance” of these subtypes of DLBCL may play a role in their responsiveness to rituximab-based immunochemoimmunotherapy. In summary, our data suggest that the Hans algorithm can predict the clinical outcome of patients with DLBCL undergoing front-line therapy with R-chemotherapy. Patients with non-GCB DLBCL while having a comparable initial complete response rate to R+CHOP had a shorter PFS and OS than GCB DLBCL patients. Non-GCB DLBCL represents a subgroup of DLBCL for which innovative therapeutic strategies targeting key regulatory pathways in the induction and/or maintenance setting are needed in an attempt to prolong PFS and improve OS. Disclosures: No relevant conflicts of interest to declare.
9
Van Meerten, Tom, Renee Bouwstra, Yuan He, de Boer Janneke, Hilde Kooistra, Rudolf Fehrmann, Emanuele Ammatuna, Gerwin Huls, and Edwin Bremer. "CD47 Expression Defines the Efficacy of Rituximab in Non-Germinal Center B-Cell (non-GCB) Diffuse Large B-Cell Lymphoma (DLBCL)." Blood 132, Supplement 1 (November 29, 2018): 2852. http://dx.doi.org/10.1182/blood-2018-99-114561.
Анотація:
Abstract CD47 is an immune-checkpoint protein that binds SIRPa on immune cells to deliver an inhibitory "don't eat me" signal. CD47 is a prominent new target in B-cell malignancies, in which CD47 antibody in combination with the CD20 antibody rituximab (R) is explored in clinical trials. Addition of R to CHOP chemotherapy significantly improves survival of patients with DLBCL, but how CD47 expression contributes to this positive impact of R on patient outcome is currently unclear. Especially in the context of the different cell-of-origin DLBCL subtypes (Germinal Center B-cell (GCB) vs non-GCB DLBCL). We therefore investigated the impact of CD47 expression on rituximab efficacy. We first studied a clinically well annotated transcriptome cohort of 939 DLBCL patients treated with either CHOP or R-CHOP, and we validated these findings in functional in vitro assays. Our analyses showed that overall survival (OS) for patients with high CD47 expression (i.e. above median) is worse compared to patients with low CD47 expression (i.e. below median) after R-CHOP (p=0.001), but not after CHOP treatment (p=0.645). Correspondingly, patients with low CD47 expression benefited most from addition of R to CHOP (HR=0.32, CI:[0.21-0.50], p<0.0001). Non--GCB patients showed a worse survival compared to GCB DLBCL patients after R-CHOP treatment (p<0.0001). Interestingly, with respect to COO classification, high expression of CD47 impacted the OS in non-GCB R-CHOP-treated patients (HR=1.9, CI:[1.14-3.26], p=0.013) but not in GCB DLBCL patients (HR=1.16, CI:[0.68-1.99], p=0.58). Importantly, high CD47 expression was found to determine the worse overall survival of non-GCB versus GCB patients (p=0.0006). No difference in OS was observed between GCB and non-GCB-patients with low CD47 expression (p=0.7662). Pro-phagocytic receptors expressed on DLBCL, i.e. SLAMF7, did not determine outcome upon R-CHOP treatment. In multivariate analysis, high CD47 expression remained significantly associated with poor survival only in non-GCB-patients. We further investigated this differential impact of CD47 in non-GCB and GCB subtypes in vitro. Non-GCB and GCB DLBCL cell lines (n=6) were mixed with allogeneic M1 macrophages and treated with a CD47 blocking antibody, which comprises human IgG4. Results confirmed that macrophage-mediated phagocytosis by R was augmented with CD47-blocking antibody only in non-GCB DLBCL cell lines, and not in GCB DLBCL cell lines. Also, CD47 blocking co-treatment also increased the number of tumor cells ingested per macrophage, with a clear significant increase in phagocytic index in non-GCB cells, but not in GCB DLBCL cells (p=0.001). In conclusion, the patient benefit of addition of R to CHOP is limited by CD47 specifically in non-GCB patients. In addition, we confirmed that CD47-blocking only augmented rituximab-mediated phagocytosis in non-GCB cell-lines. Together, these data suggest that especially non-GCB DLBCL patients with a currently worse prognosis may benefit from CD47-targeted therapy combined with rituximab. Figure. Figure. Disclosures No relevant conflicts of interest to declare.
10
Niitsu, Nozomi, Naoki Takahashi, Tadashi Yoshino, Masataka Okamoto, and Shigeo Nakamura. "Prognostic Significance of EBV Association in Diffuse Large B-Cell Lymphoma in the Rituximab Era." Blood 126, no. 23 (December 3, 2015): 3911. http://dx.doi.org/10.1182/blood.v126.23.3911.3911.
Анотація:
Abstract Introduction: Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous group of diseases in terms of morphology, immunohistochemistry and molecular features. The prognostic factors of DLBCL in the rituximab era are different from previously reported prognostic factors. Hans, et al. reported that patients with non-germinal center B-cell like (GCB)-type DLBCL had a significantly poorer prognosis than those with GCB-type DLBCL in the pre-rituximab era. In patients who received rituximab combination chemotherapy, there is a report that did not find a difference in survival ratio between those with GCB DLBCL or non-GCB DLBCL. On the other hand, there was a report that found a difference in survival ratio between patients with GCB DLBCL and those with non-GCB DLBCL. In addition, the previously reported that patients with Epstein-Barr virus (EBV)-positive DLBCL had a significantly poorer prognosis than those with EBV-negative DLBCL in the pre-rituximab era. In the present study, we considered the prognostic factors of DLBCL patients who received rituximab combined chemotherapy. Patients and Methods: The subjects were 209 DLBCL patients in whom immunohistochemical markers (CD20, CD5, CD10, BCL-2, BCL-6, MUM-1) could be analyzed. In addition, 86 patients were examined EBV-encoded RNA (EBER) in situ hybridization. Pathologic evaluation of the materials from each patient was performedat several central review meetings by six hematopathologists in the ALTSG pathology review board. Patients were treated with cyclophosphamide, vincristine, bleomycin, etoposide, doxorubicin, and prednisolone (CyclOBEAP) regimen or CHOP regimen. Rituximab was administered to all patients. One hundred forty-six DLBCL patients who underwent CHOP-like therapy were assumed as historical controls. The median follow-up period was 69 months (range, 46-88months). Results: In the R-chemotherapy and CHOP-like groups, patients with stage III or IV disease comprised 57% and 67%, respectively, patients with performance status≧2 comprised 32% and 23%, respectively, and patients with serum LDH >normal comprised 61% and 69%, respectively. There were no significant differences in clinical characteristics between the R-chemotherapy group and CHOP-like group. BCL2 was positive in 72 (55%) of the 131 patients who received the R-chemotherapy and in 71 (50%) of the 142 patients who received the CHOP-like regimen. When the 209 patients who received the R- chemotherapy group were divided into the GCB group and the non-GCB group, the GCB group consisted of 74 patients (35%) and the non-GCB group consisted of 135 patients. The relationships between immunohistological markers and outcome among the patients with DLBCL who received CHOP-like therapy were studied. CD5, CD10, and BCL6 had no prognostic impact on 5-year overall survival (OS) and progression-free survival (PFS) rates. When the patients were divided into the GCB DLBCL and non-GCB DLBCL groups, the 5-year PFS of the GCB group was 78% and that of the non-GCB group was 48% (p=0.0008). Next, the effect of rituximab with chemotherapy was examined. CD5, CD10, BCL2, BCL6, and MUM-1 had no prognostic impact on 5-year OS and PFS rates. When the patients were divided into the GCB DLBCL (n=74) and non-GCB DLBCL (n=135) groups, the 4-year PFS of the GCB group was 79% and that of the non-GCB group was 73%, showing no significant difference. We also evaluated the significance of EBER expression among patients by incorporating the EBV-positive DLBCL (n=14) and EBV-negative DLBCL (n=72).There were no significant differences in immunophenotyping analysis between the EBV-positive DLBCL and EBV-negative DLBCL. As for EBER expression in DLBCL, the 4-year PFS of the EBER-positive group was 37% and that of the EBER-negative group was 75% (P=0.007), indicating that the EBER-positive group showed significantly poorer prognosis. The 4-year OS of the EBER-positive group was 50% and the EBER-negative group was 86% (P=0.0005). Conclusions: The EBER may be an important prognostic factor in patients with DLBCL who underwent R-chemotherapy therapy. Disclosures No relevant conflicts of interest to declare.
Дисертації з теми "Gcb-Dlbcl":
1
Prévaud, Léa. "Rôle de la sous-unité c-Rel NFkB dans les Lymphômes B Diffus à Grandes Cellules du Centre Germinatif (GCB-DLBCLs) : établissement d'un modèle murin préclinique." Electronic Thesis or Diss., Limoges, 2023. http://www.theses.fr/2023LIMO0108.
Анотація:
Le facteur de transcription Rel/NF-kB inclut 5 sous-unités (SU), p50, p52, c-Rel, RelA et RelB qui s'associent en dimères. NF-κB est au cœur de l'ontogénie des lymphocytes B matures dans les centres germinatifs (CG) pour c-Rel et RelB et lors de la différentiation en plasmocyte pour RelA. Le lymphome diffus à grandes cellules (DLBCL) représente plus de 80% des lymphomes B agressifs. Nous avons publié que les SU NF-kB doivent être prises en compte de façon différentielle, tel que RelB est un marqueur de mauvais pronostic, RelA est la SU du sous-type moléculaire ABC (activated B cell) et cRel celle des GCB (germinal center B cell)-DLBCL avec une signature transcriptomique nouvelle propre. Le présent projet consiste à comprendre mécanistiquement comment c-Rel induit la transformation d'un lymphocyte B du CG. Nous avons établi un nouveau modèle murin de surexpression de c-Rel (avec YFP) dans quelques lymphocytes B du CG (tdTomato-AID-Creert2) et testons l'émergence clonale d'une tumeur. L'originalité de ce modèle inductible tient au fait qu'il permet de suivre la compétition entre les B des CG surexprimant c-Rel (tdTomato et YFP) par rapport à leur contrepartie normale (tdTomato)The transcription factor Rel/NF-kB includes 5 subunits (SU), p50, p52, c-Rel, RelA and RelB which associate into dimers. NF-κB is at the heart of the ontogeny of mature B lymphocytes in the germinal centers (GC) for c-Rel and RelB and during plasma cell differentiation for RelA. Diffuse large cell lymphoma (DLBCL) represent more than 80% of aggressive B-cell lymphomas. We have published that NF-kB SUs must be taken into account differentially, such that RelB is a marker of poor prognosis, RelA is the SU of the ABC molecular subtype (activated B cell) and cRel that of GCB (germinal center B cell)-DLBCL with a novel clean transcriptomic signature. This project consists of understanding mechanistically how c-Rel induces the transformation of a GC B lymphocyte. We have established a new mouse model of c-Rel overexpression (with YFP) in some CG B lymphocytes (tdTomato-AID-Creert2) and are testing the clonal emergence of a tumor. The originality of this inducible model relies in the fact that it makes it possible to follow the competition between the B of the GCs on expressed c-Rel (tdTomato and YFP) compared to their normal counterpart (tdTomato)
2
Wu, Yen-Fei, and 吳彥霏. "The Role of Galectin-9 in Germinal Centre B-cell-like Diffuse Large B Cell Lymphoma (GCB-DLBCL)." Thesis, 2016. http://ndltd.ncl.edu.tw/handle/72125881113790583302.
Анотація:
碩士國立臺灣大學
免疫學研究所
104
Galectin-9, a tandem-repeat type galectin, was first identified in patients with a nodular sclerosis type of Hodgkin’s disease. Previous studies demonstrated various regulatory roles of galectin-9 in the immune responses. However, role of galectin-9 in cancer biology remains elusive. Here, we found galectin-9 expression in germinal centre B-cell-like diffuse large B cell lymphoma (GCB DLBCLs) was up-regulated amongst germinal center lymphomas. To determine the role of elevated galectin-9 expression in vivo, we used NOD/SCID xenograft model of GCB DLBCLs. Strikingly, we observed a dramatic reduction of tumor volume and weight in mice receiving galectin-9 knockdown GCB DLBCL cells. Interestingly, knockdown of galectin-9 did not affect the tumorigenicity in NOD scid gamma (NSG) xenograft model, which implied natural killer (NK) cells might be responsible for the reduced tumor size in NOD/SCID mice. Thus, depletion of NK cells was achieved by anti-asGM1 antibody in NOD/SCID mice. As a result, we found partially restored tumorigenicity in NOD/SCID mice engrafted with galectin-9 knockdown GCB DLBCLs after NK cell depletion. Moreover, tumor-infiltrating NK cells were significantly increased in galectin-9-depleted tumors in NOD/SCID mice. In term of molecular mechanisms, knockdown of galectin-9 induces neither apoptosis nor cell cycle arrest in GCB DLBCLs. On the other hand, we found that the level of c-Jun, a regulator in tumor microenvironment, was decreased in galectin-9 knockdown GCB DLBCL tumors. These data suggested that galectin-9 derived from GCB-DLBCL might cause the immune escape through inhibiting NK cell activity.
Частини книг з теми "Gcb-Dlbcl":
1
Abraham Jacob, Linu, and Animesh Gupta. "DLBCL Subtypes and Prognosis Based on Immunophenotyping." In Lymphoma - Recent Advances [Working Title]. IntechOpen, 2023. http://dx.doi.org/10.5772/intechopen.109216.
Анотація:
DLBCL is the most common type of NHL diagnosed in the world. It is a highly heterogeneous disease with variable prognosis and is generally managed with standard chemo-immunotherapy and its variations. Immunohistochemistry has been found to be useful method to both sub-classify and to predict prognosis of this disease. IHC utilises various CD markers like CD10, BCL2 and IRF4 to divide DLBCL into GCB and non-GCB subtype. In clinical trials, GCB subtype has been shown to have a better prognosis and a response to treatment when compared to non-GCB subtype. Double hit/double expressor is a newer variant of DLBCL that stains positive for MYC and BCL2 or BCL6 and has been found to do better with more aggressive forms of therapy. Significance of various other CD markers is still largely unknown and further research is required in this area to better elucidate their clinical application.
Тези доповідей конференцій з теми "Gcb-Dlbcl":
1
Koning, Marvyn T., Rudolf Übelhart, Arjen H. G. Cleven, Willem H. Zoutman, Sander A. J. van der Zeeuw, Philip Kluin, Marieke Griffioen, et al. "Abstract LB-012: Autonomous, antigen-independent B-cell receptor signalling as a novel pathogenetic mechanism in non-GCB DLBCL." In Proceedings: AACR 107th Annual Meeting 2016; April 16-20, 2016; New Orleans, LA. American Association for Cancer Research, 2016. http://dx.doi.org/10.1158/1538-7445.am2016-lb-012.
2
Maerevoet, Marie, Jason Westin, Catherine Thieblemont, Josee Zijlstra, Brian T. Hill, Fatima De La Cruz Vicente, Sylvain Choquet, et al. "Abstract CT132: A Phase 2b randomized study of selinexor in patients with relapsed/refractory Diffuse Large B-Cell Lymphoma (DLBCL) demonstrates durable responses in both GCB & Non-GCB subtypes." In Proceedings: AACR Annual Meeting 2017; April 1-5, 2017; Washington, DC. American Association for Cancer Research, 2017. http://dx.doi.org/10.1158/1538-7445.am2017-ct132.
3
Lin, Xiaoyu, Xiaoli Huang, Aparna Sarthy, Terry Magoc, Daniel Albert, Lloyd Lam, Tamar Uziel, et al. "Abstract 4706: ABBV-075 exhibits robust in vitro and in vivo activities against the ABC and GCB subtypes of DLBCL." In Proceedings: AACR 107th Annual Meeting 2016; April 16-20, 2016; New Orleans, LA. American Association for Cancer Research, 2016. http://dx.doi.org/10.1158/1538-7445.am2016-4706.
4
Kawagishi, Aki, Hiroki Irie, Yoshio Ogino, Hideya Komatani, and Teruhiro Utsugi. "Abstract A274: Novel SYK inhibitors have demonstrated potent antiproliferative effects in both ABC- and GCB-DLBCL cell lines via suppression of multiple pathways downstream of the B-cell receptor." In Abstracts: AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics--Oct 19-23, 2013; Boston, MA. American Association for Cancer Research, 2013. http://dx.doi.org/10.1158/1535-7163.targ-13-a274.