scholarly journals Diagnosis-to-Treatment Interval Is an Important Clinical Factor in Newly Diagnosed Diffuse Large B-Cell Lymphoma and Has Implication for Bias in Clinical Trials

2018 ◽  
Vol 36 (16) ◽  
pp. 1603-1610 ◽  
Author(s):  
Matthew J. Maurer ◽  
Hervé Ghesquières ◽  
Brian K. Link ◽  
Jean-Philippe Jais ◽  
Thomas M. Habermann ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Odds Ratio ◽  
Cell Lymphoma ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Newly Diagnosed ◽  
Clinical Factors ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Purpose Selection bias in clinical trials has consequences for scientific validity and applicability of study results to the general population. There is concern that patients with clinically aggressive disease may not have enrolled in recent diffuse large B-cell lymphoma (DLBCL) trials due to the consent process and the inability to delay therapy for eligibility evaluation. We have examined the diagnosis-to-treatment interval (DTI) and its association with clinical factors and outcome in a clinic-based observational cohort of patients with DLBCL from the United States. Validation of results was performed in an independent, clinical trial-based cohort from Europe. Patients and Methods Patients were prospectively enrolled in the University of Iowa and Mayo Clinic Specialized Programs of Research Excellence Molecular Epidemiology Resource (MER; N = 986) or the Lymphoma Study Association (LYSA) LNH-2003 clinical trials program (N = 1,444). All patients received anthracycline-based immunochemotherapy at initial diagnosis. Associations of DTI with clinical factors and outcome were examined. Outcome was assessed using event-free survival at 24 months from diagnosis (EFS24). Results Median (range) DTI was 15 days (0 to 155 days in the MER and 23 days (0 to 215 days) in LYSA. Shorter DTI was strongly associated with adverse clinical factors, including elevated lactate dehydrogenase levels, poor performance status, B symptoms, and higher International Prognostic Index in both cohorts (all P < .001). Longer DTI was associated with improved EFS24 in both the MER (per-week odds ratio, 0.80; 95% CI, 0.74 to .0.87) and LYSA (per-week odds ratio, 0.90; 95% CI, 0.86 to 0.94); association with EFS24 remained significant after adjustment for International Prognostic Index. Conclusion DTI is strongly associated with prognostic clinical factors and outcome in newly diagnosed DLBCL. DTI should be reported in all clinical trials of newly diagnosed DLBCL and future trials should take steps to avoid selection bias due to treatment delay.

Lymphocyte Count Persistence and Early Recovery Predicts Superior Survival and Is Independent of the International Prognostic Index in Patients Treated with CHOP Chemotherapy for Diffuse Large B Cell Lymphoma.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3252-3252 ◽  
Author(s):  
Luis F. Porrata ◽  
Kay M. Ristow ◽  
Svetomir N. Markovic ◽  
Daniel Persky ◽  
Thomas M. Habermann
Keyword(s):  
Cell Lymphoma ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Newly Diagnosed ◽  
Chop Chemotherapy ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract The peripheral blood absolute lymphocyte count (ALC) post-autologous stem cell transplantation is an independent predictor for survival in non-Hodgkin’s lymphoma. The role of ALC recovery during and after standard CHOP chemotherapy for newly diagnosed diffuse large B cell lymphoma (DLBCL) has not been reported. We hypothesized that ALC recovery during/after CHOP chemotherapy has a direct impact on survival. 135 consecutive newly diagnosed patients with DLBCL treated with CHOP from 1994 through 2000 were retrospectively analyzed. The primary end point was to assess the role of ALC recovery during and after CHOP on progression-free survival (PFS) and overall survival (OS). The ALC recovery before each of the 6 cycles and at 3 months follow-up after completion of therapy were analyzed. Of the 135 patients, 41 patients received concomitant radiation therapy. The median age was 64 years (range: 21–83) and median follow-up was 46 months (range: 1–124). Superior OS and PFS were identified in patients achieving the ALC cut-off value that discriminated clinical outcomes at a high level of significance for blood counts obtained before cycles 1 (ALC ≥ 1.5 x 109/L, OS = not reached vs 54 months, p< 0.0048; PFS = not reached vs 23 months, p <0.0005), 2 (ALC ≥1.5 x 109/L, OS = not reached vs 59 months, p <0.0255; PFS = not reached vs 30 months, p <0.0082), 3(ALC ≥1.2 x 109/L, OS = not reached vs 59 months, p<0.0074; not reached vs 30 months, p <0.0060), and at 3 months (ALC ≥ 1.2 x 109/L, OS = not reached vs 60 months, p< 0.0080; PFS = not reached vs 42 months, p < 0.0017). Similar cut-off points for cycles 4 through 6 could not be identified. The ALC recovery between each cycles 1–3 and at 3 months were not independent of each other. Multivariate analysis demonstrated ALC for cycles 1–3 and at 3 months post CHOP to be independent prognostic factor for OS and PFS when compared to other significant prognostic factors including International Prognostic Index and radiation therapy. Patients were stratified into three groups based on whether or not they achieved cut-off values of ALC in the first 3 cycles: group I= ALC achieved in at least 2 of 3 cycles; group II= ALC achieved in only 1/3 cycles; and group III= ALC cut-off not achieved. A trend towards worse OS (p< 0.0035) (Figure 1) and PFS (p< 0.0003) was identified if patients did not achieve any of the cut-off values of ALC in the first 3 cycles. These data further support the hypothesis that there is a critical role of lymphocyte (immune) recovery during and after CHOP chemotherapy in DLBCL.

scholarly journals Circulating long non-coding RNAs HOTAIR, Linc-p21, GAS5 and XIST expression profiles in diffuse large B-cell lymphoma: association with R-CHOP responsiveness

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mahmoud A. Senousy ◽  
Aya M. El-Abd ◽  
Raafat R. Abdel-Malek ◽  
Sherine M. Rizk
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
Expression Profiles ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Diagnostic Tools ◽  
Large B Cell Lymphoma ◽  
Non Coding Rnas ◽  
Large B Cell

AbstractThe reliable identification of diffuse large B-cell lymphoma (DLBCL)-specific targets owns huge implications for its diagnosis and treatment. Long non-coding RNAs (lncRNAs) are implicated in DLBCL pathogenesis; however, circulating DLBCL-related lncRNAs are barely investigated. We investigated plasma lncRNAs; HOTAIR, Linc-p21, GAS5 and XIST as biomarkers for DLBCL diagnosis and responsiveness to R-CHOP therapy. Eighty-four DLBCL patients and thirty-three healthy controls were included. Only plasma HOTAIR, XIST and GAS5 were differentially expressed in DLBCL patients compared to controls. Pretreatment plasma HOTAIR was higher, whereas GAS5 was lower in non-responders than responders to R-CHOP. Plasma GAS5 demonstrated superior diagnostic accuracy (AUC = 0.97) whereas a panel of HOTAIR + GAS5 superiorly discriminated responders from non-responders by ROC analysis. In multivariate analysis, HOTAIR was an independent predictor of non-response. Among patients, plasma HOTAIR, Linc-p21 and XIST were correlated. Plasma GAS5 negatively correlated with International Prognostic Index, whereas HOTAIR positively correlated with performance status, denoting their prognostic potential. We constructed the lncRNAs-related protein–protein interaction networks linked to drug response via bioinformatics analysis. In conclusion, we introduce plasma HOTAIR, GAS5 and XIST as potential non-invasive diagnostic tools for DLBCL, and pretreatment HOTAIR and GAS5 as candidates for evaluating therapy response, with HOTAIR as a predictor of R-CHOP failure. We provide novel surrogates for future predictive studies in personalized medicine.

scholarly journals Concurrent Expression of MYC and BCL2 in Diffuse Large B-Cell Lymphoma Treated With Rituximab Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone

2012 ◽  
Vol 30 (28) ◽  
pp. 3452-3459 ◽  
Author(s):  
Nathalie A. Johnson ◽  
Graham W. Slack ◽  
Kerry J. Savage ◽  
Joseph M. Connors ◽  
Susana Ben-Neriah ◽  
...  
Keyword(s):  
Protein Expression ◽  
B Cell ◽  
Cell Lymphoma ◽  
Molecular Subtype ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Bcl2 Protein ◽  
Large B Cell

Purpose Diffuse large B-cell lymphoma (DLBCL) is curable in 60% of patients treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). MYC translocations, with or without BCL2 translocations, have been associated with inferior survival in DLBCL. We investigated whether expression of MYC protein, with or without BCL2 protein expression, could risk-stratify patients at diagnosis. Patients and Methods We determined the correlation between presence of MYC and BCL2 proteins by immunohistochemistry (IHC) with survival in two independent cohorts of patients with DLBCL treated with R-CHOP. We further determined if MYC protein expression correlated with high MYC mRNA and/or presence of MYC translocation. Results In the training cohort (n = 167), MYC and BCL2 proteins were detected in 29% and 44% of patients, respectively. Concurrent expression (MYC positive/BCL2 positive) was present in 21% of patients. MYC protein correlated with presence of high MYC mRNA and MYC translocation (both P < .001), but the latter was less frequent (both 11%). MYC protein expression was only associated with inferior overall and progression-free survival when BCL2 protein was coexpressed (P < .001). Importantly, the poor prognostic effect of MYC positive/BCL2 positive was validated in an independent cohort of 140 patients with DLBCL and remained significant (P < .05) after adjusting for presence of high-risk features in a multivariable model that included elevated international prognostic index score, activated B-cell molecular subtype, and presence of concurrent MYC and BCL2 translocations. Conclusion Assessment of MYC and BCL2 expression by IHC represents a robust, rapid, and inexpensive approach to risk-stratify patients with DLBCL at diagnosis.

scholarly journals Diffuse large B-cell lymphoma: A single-institution experience of patient outcomes.

2016 ◽  
Vol 34 (7_suppl) ◽  
pp. 271-271
Author(s):  
Ryan James Chan ◽  
Rasna Gupta ◽  
Sindu Mary Kanjeekal ◽  
Mohammed Jarrar ◽  
Amin Kay ◽  
...  
Keyword(s):  
British Columbia ◽  
B Cell ◽  
Cell Lymphoma ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Canadian Province ◽  
Large B Cell Lymphoma ◽  
Cancer Program ◽  
Large B Cell

271 Background: The Windsor Regional Cancer Program (WRCP) was determined to have consistently been a top performer in time to treatment of diffuse large B cell lymphoma in this Canadian province (http://www.csqi.on.ca/by_type_of_cancer/lymphoma/lymphoma_treatment/). We endeavored to determine whether faster time to diagnosis and treatment for diffuse large B-cell lymphoma (DLBCL) influenced the IPI score (International Prognostic Score), thereby predicting an improved clinical outcome in these presenting patients. Methods: The WRCP services a catchment area of 650,000 people. A retrospective chart review was conducted for patients diagnosed with DLBCL at the Windsor Regional Cancer Program (WRCP) between 2006-2012. Information collected included the five factors for scoring by the International Prognostic Index (IPI) – age, performance status, LDH, stage, and number of extranodal sites – chemotherapy regimen, relapses, existence of second malignancies, cause of death, and dates of diagnosis, last follow-up, and death. We analyzed the relationship between prognostic factors and these clinical outcomes, and also compared the IPI scores for this cohort of patients against a similar population in another Canadian province, British Columbia. Results: It is established that compared to other cancer centres in Ontario, the WRCP is consistently reporting a shorter diagnosis to treatment metric when compared to their counterparts in Ontario, Canada. When compared to historical Canadian data, presenting IPI scores for DLBCL patients were lower on average for patients treated at the WRCP than those reported in British Columbia, Canada by Sehn et al. [Sehn, L. H., et al. (2007). The revised International Prognostic Index is a better predictor of outcome than the standard IPI for patients with diffuse large B-cell lymphoma treated with R-CHOP. Blood, 109(5), 1857-1861.]. Conclusions: A lower presenting IPI score is known to be correlated improved lymphoma related outcome. With attention to the metric of diagnosis to treatment < 30 days for diffuse large B cell lymphoma, we expect an improved lymphoma related outcome for our patients. We recommend ongoing attention to this metric, in order to improve outcomes for our patients.

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