The Immunohistochemical Profile and Other Prognostic Factors In Patients with Newly Diagnosed Diffuse Large B-Cell Lymphoma Treated with R-CHOP

Abstract Abstract 4126 Introduction: The immunohistochemical (IHC) profile as described by Hans and colleagues has emerged as a potential prognostic and predictive factor in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) treated with chemotherapy. However, its role has not been completely elucidated. The main objective of this patient-level meta-analysis was to evaluate the IHC profile as a prognostic and predictive indicator in newly diagnosed DLBCL patients treated with R-CHOP. Secondary objectives were to identify potential novel prognostic factors in these patients. Methods: Patient-level clinical data was requested from 13 research groups that published studies on the role of the IHC profile in prognosis for DLBCL patients treated exclusively with R-CHOP. Six groups (46%) submitted their data, accounting for a total of 701 patients. The requested clinical data included age, sex, performance status, LDH levels, number of extranodal sites, clinical stage, expression of CD10, BCL-6 and MUM1, IHC profile, type of response, outcome and overall survival (OS). Logistical regression analyses were used to identify independent variables associated with overall and complete response rates. Univariate survival curves were estimated using the Kaplan-Meier method and compared using the log-rank test. Multivariate analysis was performed using the Cox proportional-hazard regression test. P-values of <0.05 were considered statistically significant. Results: The median age was 63 years (range 16–90 years), 54% were men, 59% were 60 years or older, 24% had an ECOG ≥2, 55% had elevated LDH levels, 15% had ≥2 extranodal sites involved, 52% had stage III/IV and 48% had a non-germinal center (NGC) IHC profile. The overall response rate was 92% with complete responses seen in 78% and partial responses in 14%. The median follow-up was 34 months. In the logistical regression analysis, age ≥70, high LDH, ECOG ≥2, stage III/IV and a NGC profile were associated with improved overall response, and MUM1 expression, ECOG ≥2 and stage III/IV were associated with improved complete response. In the survival analysis, the estimated 5-year OS was 66% and the median OS was not reached. Age ≥60 years, elevated LDH levels and NGC IHC profile (Figure) were not associated with worse OS. In the multivariate analysis, age ≥70 years, male sex, ECOG ≥2 and clinical stage III/IV were independent prognostic factors for OS. A prognostic score was formulated using these 4 prognostic factors and then compared against the IPI and R-IPI scores. This novel score and the IPI score were the only independent factors for OS with HR 1.4 (95% CI 1.19–1.64) and 1.38 (95% CI 1.15–1.67) with p<0.0001 and p=0.0006, respectively. Conclusion: The IHC profile is not a prognostic indicator for OS, and it is predictive of overall response but not complete response in newly diagnosed patients with DLBCL treated with R-CHOP. Age ≥70, male sex, ECOG ≥2 and stage III/IV were independent prognostic factors for OS. A score consisting of these 4 factors showed a significant prognostic value in DLBCL patients treated with R-CHOP. Disclosures: No relevant conflicts of interest to declare.

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High Incidence of Antiphospholipid Antibodies in Newly Diagnosed Patients With Lymphoma and a Proposed aPL Predictive Score

Clinical and Applied Thrombosis/Hemostasis ◽

10.1177/1076029620928392 ◽

2020 ◽

Vol 26 ◽

pp. 107602962092839

Author(s):

Smith Kungwankiattichai ◽

Yupa Nakkinkun ◽

Weerapat Owattanapanich ◽

Theera Ruchutrakool

Keyword(s):

Cell Lymphoma ◽

Significant Risk ◽

Stage Iv ◽

B Cell Lymphoma ◽

Predictive Score ◽

Newly Diagnosed ◽

Large B Cell Lymphoma ◽

High Incidence ◽

Male Sex

Given that the presence of antiphospholipid (aPL) antibodies has been proposed to be associated with thrombosis in newly diagnosed patients with lymphoma, we conducted a prospective cohort study on these patients. In all, 154 patients were enrolled. More than half were advanced-stage diffuse large B-cell lymphoma. Approximately one-third (35.7%) of the patients had the presence of aPLs, with single-, double-, and triple-aPL positivities of 29.9%, 5.2%, and 0.6%, respectively. Of the 154 patients, 8 (5.19%) developed symptomatic thrombosis during follow-up. There were no significant differences in the incidences of thrombosis for the aPL-positive and aPL-negative groups (5.5% vs 5.1%; P = 1.000). In a multivariate analysis, patients with male sex and lymphoma stage IV were significant risk factors for aPL positivity, with odds ratio [OR] = 2.22 (95% CI: 1.11-4.45), P = .025, and OR: 2.34 (95% CI: 1.17-4.67), P = .016, respectively. An aPL predictive score of ≥−1 was predictive of aPL positivity, with a sensitivity of 83.6% and specificity of 34.3%.

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Improved Progression-Free Survival for Bulky and Non-Bulky Advanced Stage Diffuse Large B-Cell Lymphoma with Consolidative Radiation Therapy: A Bi-Institutional Analysis

10.21203/rs.3.rs-137697/v1 ◽

2021 ◽

Author(s):

Yusef Ali Syed ◽

Cecilia Jiang ◽

Jeffrey Switchenko ◽

Khadija Kirmani ◽

Chris Kelsey ◽

...

Keyword(s):

Systemic Therapy ◽

Cell Lymphoma ◽

Progression Free Survival ◽

B Cell Lymphoma ◽

Complete Response ◽

Stage Iii ◽

Bulky Disease ◽

Free Survival ◽

Large B Cell Lymphoma

Abstract Background: The role of consolidative radiation therapy (RT) for advanced stage diffuse large B-cell lymphoma (DLBCL) is not fully established. Retrospective data provide evidence for the use of consolidative RT in stage III-IV DLBCL and emerging data from randomized studies address the role of RT in bulky disease for these patients.Methods: Patient with stage III-IV DLBCL treated at two institutions who achieved clinical complete response to systemic therapy were included. Kaplan-Meier analysis was performed to determine the impact of consolidative RT. Univariate and multivariable analyses were performed using a Cox proportional hazards model.Results: One hundred eighty-eight patients received systemic therapy consisting of R-CHOP (79%), another Rituximab-based regimen (9%), or chemotherapy alone (12%). Clinical response was assessed using conventional CT or PET-CT. Sixty-eight patients (36%) received consolidative RT (median dose 30 Gy). Consolidative RT conferred a 36.7% absolute benefit in five-year progression-free survival (85.9% vs. 49.2%, log rank p < 0.0001), and a 14.5% absolute benefit in five-year overall survival (87.4% vs. 72.9%, log rank p = 0.0134). On multivariable analysis, consolidative RT was associated with improved PFS (HR 0.23, 95% CI 0.10-0.52, p < 0.001). Patients receiving consolidative RT demonstrated significantly improved PFS for tumors measuring both <5 cm (log rank p = 0.0454) and ³5 cm (log rank p = 0.0003).Conclusions: For patients with stage III-IV DLBCL who achieve clinical complete response after systemic therapy, consolidative RT improves PFS for all patients, including those with non-bulky disease. This benefit persists in the setting of rituximab-based systemic therapy.

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Clinicopathological Differences Between Asian and Western Patients with De Novo Diffuse Large B Cell Lymphoma Treated with R-CHOP

Blood ◽

10.1182/blood.v118.21.2665.2665 ◽

2011 ◽

Vol 118 (21) ◽

pp. 2665-2665

Author(s):

Natalie Sinclair ◽

Brady E Beltran ◽

Moo-Kon Song ◽

Ivana Ilic ◽

Sirpa Leppa ◽

...

Keyword(s):

Prognostic Factors ◽

Research Funding ◽

De Novo ◽

Cell Lymphoma ◽

Clinical Stage ◽

Performance Status ◽

B Cell Lymphoma ◽

Advanced Clinical Stage ◽

Large B Cell Lymphoma ◽

Large B Cell

Abstract Abstract 2665 Introduction: Little is known on the racial differences in characteristics and outcomes of patients with a diagnosis with diffuse large B-cell lymphoma (DLBCL) treated with rituximab-containing regimens. The aim of this retrospective study is to compare the clinicopathological characteristics, prognostic factors and outcomes of Asian and Western patients with a diagnosis of de novo DLBCL treated with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP). Patients and Methods: Patient-level data was collected from 8 centers (USA, Italy, Sweden, Finland, Croatia, Japan, Korea and China). This study was approved by the Institutional Review Board at each of the participant centers. All patients were diagnosed with de novo DLBCL and treated with R-CHOP administered every 3 weeks. HIV-positive and primary brain DLBCL were excluded. The requested clinical data included age, sex, performance status, lactate dehydrogenase (LDH) levels, number of extranodal sites, clinical stage, expression of CD10, BCL6 and MUM1/IRF4, response to chemotherapy, outcome and overall survival (OS). Patients were divided in Asian and Western, according to the country of report. Comparison between groups was performed with Mann-Whitney and Chi square tests for continuous and categorical variables, respectively. Univariate survival curves were estimated using the Kaplan-Meier method and compared using the log-rank test. Multivariate analysis was performed using the Cox proportional-hazard regression test. P-values of <0.05 were considered statistically significant. Results: A total of 712 patients, 455 Asian and 257 Western patients were included in this study. Western patients were more likely to present with elevated LDH levels (70% vs. 48%; p<0.001), advance clinical stage (58% vs. 49%; p=0.02) and a non-germinal center immunohistochemical profile (53% vs. 43%; p=0.01). Additionally, Western patients were more likely to present with low risk IPI scores (p=0.003 for trend), and had higher complete response (CR) rates (91% vs. 76%; p<0.001). There were no statistical differences between the 2 groups on age at diagnosis, sex distribution, ECOG performance status, number of extranodal sites, overall response rates and proportion of deaths. After a median follow-up of 36 months, there was no difference in median overall survival (OS; not reached in both groups) or estimated 5-year OS (66% vs. 62%; p=0.67) (Figure). In the univariate analyses, ECOG >1, elevated LDH levels and advanced clinical stage were significantly associated with a worse median OS in Westerners (p<0.01 each factor) while ECOG >1, >1 extranodal sites and advanced clinical stage were significant adverse factors for Asians (p<0.01 each factor). In the multivariate analyses, ECOG >1 and advanced clinical stage were independent prognostic factors associated with a worse median OS in Westerners and Asians (p<0.01, p=0.03, and p<0.01, p<0.01, respectively). Elevated LDH level was an adverse independent prognostic factor for Western patients only (p=0.04). Conclusions: Asian and Western patients with de novo DLBCL present with distinct clinical and pathological characteristics, and although the CR rate to standard R-CHOP was higher in Westerners than in Asians, the final outcome, prognostic factors and median and 5-year OS rates are similar in both populations. Disclosures: Castillo: GlaxoSmithKline: Research Funding; Millennium Pharmaceuticals: Research Funding.

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HYPOGAMMAGLOBULINEMIA AND HYPOCOMPLEMENTEMIA AS STRONG PROGNOSTIC FACTORS IN NEWLY DIAGNOSED DIFFUSE LARGE B CELL LYMPHOMA

Hematological Oncology ◽

10.1002/hon.86_2631 ◽

2019 ◽

Vol 37 ◽

pp. 416-418

Author(s):

W. Xu ◽

B. Pan ◽

H. Zhu ◽

L. Wang ◽

L. Fan ◽

...

Keyword(s):

Prognostic Factors ◽

B Cell ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Newly Diagnosed ◽

Large B Cell Lymphoma ◽

Large B Cell

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Clinical Significance of MYC, BCL2 and BCL6 Rearrangement and Protein Expression in GCB and Non-GCB Type Diffuse Large B-Cell Lymphoma

Blood ◽

10.1182/blood.v126.23.1445.1445 ◽

2015 ◽

Vol 126 (23) ◽

pp. 1445-1445

Author(s):

Keisuke Kawamoto ◽

Jun Takizawa ◽

Hiroaki Miyoshi ◽

Noriaki Yoshida ◽

Yasuhiko Shibasaki ◽

...

Keyword(s):

Prognostic Factors ◽

Prognostic Factor ◽

B Cell ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Prognostic Indicators ◽

Newly Diagnosed ◽

Poor Prognostic Factor ◽

Large B Cell Lymphoma ◽

Large B Cell

Abstract Background: Diffuse large B-cell lymphoma, not other specified (DLBCL, NOS) is the most common type of malignant lymphoma and accounts for approximately one-third of all non-Hodgkin lymphomas. Translocation of MYC, BCL2, and BCL6 genes detected by fluorescence in-situ hybridization (FISH) were found in approximately 10%, 14%, and 20% DLBCL, respectively. MYC translocation is already reported to be an independent poor prognostic factor in DLBCL. Immunohistochemical(IHC) analysis has revealed that concurrent protein expression of MYC and BCL2 could be a predictive factor for overall survival (OS). However, the relationship between translocation and expression of MYC, BCL2 and BCL6 is still unknown, and it is not clear what proportion of MYC and BCL2 IHC is predictive for OS. Objectives: The purpose of this study was to clarify the clinical prognostic value of immunostaining and chromosomal translocation of MYC, BCL2 and BCL6 among the populations in whom these results were investigated. Patients and Methods: Sixty-one adult patients, newly diagnosed as DLBCL, NOS between October 2003 and October 2012 at Niigata University Hospital, were analyzed retrospectively. MYC, BCL2 and BCL6 rearrangements were detected by FISH, and the expression of MYC, BCL2, and BCL6 proteins were investigated by IHC. To assess the proportion of these proteins, we created a tissue microarray (TMA). The median age was 62 years (range: 17-85 years), and the median follow up period was 42 months (range: 2-127 months). All patients were treated with R-CHOP or R-CHOP-like regimens. OS was estimated by the Kaplan-Meier method. Multivariate Cox regression for OS was used to identify the independent prognostic factors. Results: According to univariate analysis, MYC rearrangement (10%) was a prognostic factor (P = 0.026); however, BCL2 and BCL6 translocation were not prognostic indicators (11%, P = 0.899; 13%, P = 0.819, respectively). On the other hand, the expression of MYC detected by IHC showed no statistical significance for OS, even if the cut-off level by MYC and BCL6 immunostaining was modified. However, if we divided the patients into two groups, i.e., those with 0-9% and those with ≥10% expression of BCL2 immunostaining, ≥10% expression of BCL2 may be a prognostic factor (P = 0.0087). We subsequently analyzed whether the concurrent expression of MYC and BCL2 or that of MYC and BCL6 would be prognostic factors for OS. In this study, patients with ≥30% expression of MYC and ≥30% expression of BCL2 showed poor prognosis compared to other patients (P = 0.00234, 5-year OS 42%, 84% respectively). Furthermore, we divided the patients in two groups i.e., the germinal center B-cell-like (GCB) type and non-GCB type as described by Hans et al., and the non-GCB type was observed to be a poor prognostic factor in both groups (P = 0.013). Further, we investigated whether these factors could be independent factors for OS. Multivariate analysis revealed IPI3-5 (HR, 3.1510 [range: 1.181-3.151), P = 0.022), MYC translocation (HR, 3.686 [range: 1.113-12.210], P = 0.033), and MYC (≥30%)/BCL2 (≥30%) double-expression (HR, 4.051 [range: 1.447-11.340], P = 0.0078) were independent poor prognostic indicators in newly diagnosed DLBCL patients treated with R-CHOP or R-CHOP like regimens. Conclusions MYC translocation by FISH and MYC (≥30%)/BCL2 (≥30%) double-expression detected by IHC could be independent prognostic factors for OS. However, MYC expression is not a surrogate marker for MYC translocation by FISH. In conclusion, FISH analysis of MYC translocation and MYC and BCL2 co-expression are important for predicting the prognosis of DLBCL. These results indicate that further validation is required using another population. Disclosures No relevant conflicts of interest to declare.

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The Effect of Adding Rituximab to CHOP-Based Therapy on Clinical Outcomes for Patients In Different Subgroups of DLBCL

Blood ◽

10.1182/blood.v116.21.4893.4893 ◽

2010 ◽

Vol 116 (21) ◽

pp. 4893-4893

Author(s):

Shenxian Qian ◽

Daquan Gao ◽

Pengfei Shi ◽

Junfeng Tan ◽

Ling Wang ◽

...

Keyword(s):

B Cell ◽

Germinal Center ◽

Response Rate ◽

Complete Response Rate ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Complete Response ◽

Newly Diagnosed ◽

Large B Cell Lymphoma ◽

Large B Cell

Abstract Abstract 4893 The addition of rituximab to cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) has been shown to improve the outcome in all age groups with newly diagnosed diffuse large B-cell lymphoma (DLBCL). We conducted a retrospective analysis to evaluate the impact on clinical outcomes of adding rituximab to cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) treatment for diffuse large B-cell lymphoma (DLBCL) patients in china. A propensity score method was used to compensate for the non-randomized study design. From January 2004 to December 2009, 68 patients were newly diagnosed with DLBCL Using Hans' algorithm based on CD10, BCL-6, and MUM1, the non-germinal center (N-GCB) subgroup 45(66.2%) and germinal center B-cell-like (GCB) 23(33.8%). 32 in the rituximab plus CHOP-based chemotherapy (R+) group, and 36 in the CHOP-based chemotherapy only (R-) group. The complete response rate was significantly higher in the R+ group than in the R- group (81.1 vs. 68.1%, P < 0.005,); The complete response rate of N-GCB and GCB in the R+ group was78.2% and 82.1%, p>0.05 respectively. The complete response rate of N-GCB and GCB in the R- group was58.2% and 71.3 %, p P < 0.001. The rituximab can overcome poor outcomes for N-GCB subgroup of DLBCL. The progression-free survival (PFS) at 2 years was 62.4% in the R+ group and 57.0% in the R- group. The 2-year overall survival (OS) was 76.9% for the R+ group and 69.5% for the R- group, P < 0.001. The 2-year overall survival (OS) was 72% in N-GCB Subgroup and 78% in GCB Subgroup for the R+ group, and 48% in N-GCB Subgroup and 68% in GCB Subgroup for the R- group. A multivariate analysis revealed that the addition of rituximab was a strong independent prognostic factor for PFS (hazard ratio 0.64, 95% CI 0.43–0.96, P = 0.031). A subgroup analysis revealed that R+ particularly benefited N-GCB subgroup patients). IPI also showed significant impact for PFS (hazard ratio 1.72, 95% CI 1.34–2.14 for one score increase, P < 0.001 as well as OS P < 0.001. In summary, the addition of rituximab to CHOP-based chemotherapy results in better outcomes for DLBCL patients, particularly patients N-GCB subgroup of DLBCL. Disclosures: No relevant conflicts of interest to declare.

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Peripheral Absolute Neutrophil, Mmonocyte and Lymphocyte Counts and Clinical Ooutcome in Diffuse Large B-Cell Lymphoma

Blood ◽

10.1182/blood.v124.21.4416.4416 ◽

2014 ◽

Vol 124 (21) ◽

pp. 4416-4416 ◽

Cited By ~ 1

Author(s):

Yiming Chen ◽

Maria Alma Rodriguez ◽

Lei Feng ◽

Weiqi Bi ◽

Liang Zhang ◽

...

Keyword(s):

Prognostic Factors ◽

B Cell ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Newly Diagnosed ◽

Time To Event ◽

Poor Prognostic Factor ◽

Large B Cell Lymphoma ◽

Baseline Levels ◽

Large B Cell

Abstract Background Baseline levels of peripheral absolute neutrophil (ANC), lymphocyte (ALC) and monocyte (AMC) counts have prognostic value in solid tumors. There are limited data on their impact on outcomes in patients with diffuse large B-cell lymphoma (DLBCL). The present study is to confirm whether the baseline levels of peripheral ANC, ALC and AMC can predict outcomes in patients with newly diagnosed DLBCL. Patients and Methods Data from lymphoma database at the University of Texas MD Anderson Cancer Center (UTMDACC) were used. The correlation of baseline ANC, AMC and ALC with progression-free survival (PFS) and overall survival (OS) were analyzed in 817 newly diagnosed previously untreated patients with DLBCL who received frontline treatments at UTMDACC between 2000-2011. Kaplan-Meier method was used for time-to event analysis including PFS and OS. Multi Cox proportional hazards model were fitted to evaluate important patient characteristics on the time-to event endpoints. Results Median ages at diagnoses were 58 years (range, 18 to 91 years). Seventy-nine percent of patients received conventional immunochemotherapy(CHOP-R) while 21 % of patients had intensive immunochemotherapy (HyperCVAD-R or R-EPOCH) or intensive chemotherapy(n=5; HyperCVAD or R-EPOCH) due to CD 20 negative; two patients received radiation therapy only. IPI low, intermediate and high were 38%, 46% and 16%, respectively. Overall response rate was 98% with a complete remission rate of 73%. Patients with abnormal ANC (> 7.3 X109/L) had an inferior PFS (P<0.001) and OS (P<0.001) compared to patients with ANC ≤ 7.3 X109/L; patients with abnormal ALC (< 1.0 X109/L) had significant short PFS (P<0.001) and OS (P<0.001) compared to patients with ALC ≥ 1.0 X109/L; similarly, patients with abnormal AMC (> 0.7X109/L) had inferior PFS (P< 0.001) and OS (P< 0.001) compared to patients with AMC≤ 0.7 X109/L. Multivariate analysis identified abnormal ALC and AMC as an independent adverse prognostic factors for PFS (hazard ratio [HR] 1.39 and 1.49, respectively; P<0.016 and P=0.004, respectively) and abnormal ANC and AMC as an independent adverse prognostic factors for OS (P=0.017 and P=0.024, respectively; HR 1.56 and 1.42, respectively). Conclusions An abnormal Neutrophil, lymphocyte and monocyte counts in peripheral blood are independent, poor prognostic factor for PFS and OS in patients with DLBCL. Incorporation of these immunological markers into IPI prognostic model may improve outcome prediction. Disclosures No relevant conflicts of interest to declare.

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Prognostic significance of pretreatment serum free fatty acid in patients with diffuse large B-cell lymphoma in the rituximab era: a retrospective analysis

BMC Cancer ◽

10.1186/s12885-021-08963-6 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Liping Fan ◽

Qiuyan Lin ◽

Xiaoling Huang ◽

Danhui Fu ◽

Haobo Huang

Keyword(s):

Prognostic Factors ◽

Fatty Acid ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Newly Diagnosed ◽

Serum Free Fatty Acid ◽

Serum Free ◽

Large B Cell Lymphoma ◽

Pretreatment Serum ◽

Large B Cell

Abstract Background Fatty acid metabolism is reportedly associated with various cancers. However, the role of pretreatment serum free fatty acid (FFA) levels in diffuse large B-cell lymphoma (DLBCL) prognosis is still unclear, and our study aimed to better elucidate its influence on clinical outcomes. Methods The medical records of 221 newly diagnosed DLBCL patients admitted to Fujian Medical University Union Hospital from January 2011 to December 2016 were analysed retrospectively. Receiver operating characteristic curve analysis was used to determine a cut-off value for pretreatment serum FFA levels for prognostic prediction in DLBCL patients. The relationship between pretreatment serum FFA levels and clinical and laboratory parameters was analysed. Univariate and multivariate analyses were used to assess prognostic factors for overall survival (OS) and progression-free survival (PFS). Results Newly diagnosed DLBCL patients with high pretreatment serum FFA levels (≥0.495 mmol/l) had more B symptoms, higher serum lactate dehydrogenase levels (> upper limit of normal), >1 extranodal site, and higher International Prognostic Index score (3–5) compared to those with low pretreatment serum FFA levels (<0.495 mmol/l). Higher serum FFA levels were independent prognostic factors for poor OS, but not PFS. Conclusions High pretreatment serum FFA levels are associated with lower survival in untreated DLBCL patients.

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