scholarly journals Prognostic Impact of the Baseline Immunologic Profile in Patients with Aggressive B Non-Hodgkin Lymphomas

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1522-1522
Author(s):  
Safaa M. Ramadan ◽  
Giusy Ceparano ◽  
Alessandro Cignetti ◽  
Simona Sammassimo ◽  
Vincenzo Bagnardi ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Risk Group ◽  
Prognostic Impact ◽  
Bulky Disease ◽  
Non Hodgkin Lymphoma ◽  
Number Of Patients ◽  
The Impact ◽  
Immunologic Profile ◽  
Igg Level

Background The Revised- International Prognostic Index (R-IPI), the current standard prognostic tool for patients with diffuse large cell lymphoma (DLBCL), considers only patient and clinical disease characteristics. The role of host immune homeostasis as an independent prognostic indicator in different diseases including DLBCL is evolving. Rambaldi et al 2013, showed that the lymphocyte monocyte ratio (LMR) at diagnosis is a simple prognostic biomarker and independent of the R-IPI. Low level of immunoglobulin at diagnosis, in particular IgG, is associated with inferior survival in Hodgkin and Non Hodgkin lymphoma patients (NHL). In DLBCL patients who underwent autologous transplants, Brown et al 2004 documented 18 months relapse free survival of 44% if IgG levels at time of transplant are below 600 mg/dL and 63% if higher. To our knowledge, the prognostic impact of immunoglobulin levels at diagnosis in patients with aggressive B-NHL has not been investigated. Therefore, we aimed to evaluate the prognostic role of the immunologic profile in terms of the pretreatment levels LMR and of immunoglobulins in patients with aggressive B-NHL. Methods and results: We retrospectively patients diagnosed with aggressive B non-Hodgkin lymphoma (NHL) at both the European Institute of Oncology in Milan and the Mauriziano Hospital in Turin from April 2014 to October 2018. Patients with DLBCL, Burkitt, Mantle cell and follicular G3B lymphomas were eligible. All patients were treated with chemo-immunotherapy according to center guidelines and a written informed consent was obtained from all them. A total of 105 patients were included, with male predominance (60%), median age of 64.5 years (range 20-83) and ECOG score 0-1 in 66%. Stage III-IV disease was seen in 58%, extranodal involvement in 73%, bone marrow infiltration in 26%, bulky disease in 39% and high LDH in 66%. Median IgG level was 1003 (range 436-2236) and the median LMR was 2.4 (range 0.2-44.2). By univariate analysis older age, advanced stage, higher ECOG PS, 2 or more extranodal disease sites, poor R-IPI, higher LDH, low LMR ratio as well as low IgG level at diagnosis was associated with a worse 1-year PFS. LMR inferior or equal to 2.4 had 1-year PFS of 70%, compared to 90% if LMR was higher (p 0.025). Patients with IgG levels less than 1003 had 1-year PFS of 70% compared to 90% in higher IgG levels. The later, didn' t reach statistical significance, due to small number of patients, but remains clinically relevant. Interestingly, there was no correlation between the levels of IgG and the LMR. Therefore, we examined the impact of combining each to R-IPI groups. A low IgG at diagnosis worsen the PFS in patients with good or very good R-IPI with 1 year PFS 83% (95% CI 60-93%) compared 97% (95% CI 79%-100%) if IgG levels are higher. Interestingly, patients in the poor IPI risk group and high IgG levels ad 1-year PFS similar to the good risk group with low IgG levels (PFS 84%, 95% CI 57-94%). The worst PFS is seen in the group of patients with poor IPI score and low IgG, PFS 61%, (95% CI 40%-77%). Similar results were seen in case of LMR. We then examined a novel immunologic prognostic score system that includes the three factors: baselines IGg levels, LMR and the R-IPI Figure 1. Because IgG levels and LMR are independent we put the same weight on each factor as well as the R-IPI score. We gave 1 point to each factor R-IPI poor (1 point) + IgG low (1 point) + LMR low (1 point). The sum of the chosen points correlated with four risk groups: group 1 = 0 points, group =2 = 1 point, group 3= 2 points and group 4= 3 points. The 1 year PFS was 95% (95% CI 68%-99%), 94% (95% CI 77%-98%), 75% (95% CI 54%-87%), 52% (95% CI 27%-73%), respectively. Conclusion: To our knowledge, this study is the first to report the prognostic implications of pretreatment levels of immunoglobulin IgG within the immunologic profile of patients with aggressive B-NHL. Our results suggests that IgG level at diagnosis is a clinically important prognostic factor. With the proposed immunologic score, patients are reclassified into four sub-groups with 3 significantly different 1-year PFS of 95% 75%, 50% in patients with no or one poor risk factor, 2 factors or 3 factors, respectively. This study confirms that the addition of baseline immunologic profile to R-IPI in patients with aggressive B-NHL optimizes their prognostic stratification and better identify patients who are at risk of poor outcome compared to the R-IPI alone. Disclosures Saglio: BMS: Consultancy; Novartis: Consultancy; Ariad: Consultancy; Incyte: Consultancy; Pfizer: Consultancy; Jansen: Consultancy; Celgene: Consultancy.

Differential Impact of Relative Dose-Intensity Reductions (DIR) in Diffuse Large B-Cell Lymphoma (DLBCL) Treated with R-CHOP21 or R-CHOP14

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3073-3073
Author(s):  
Leyre Bento ◽  
Francesc Garcia ◽  
Antonia Maria Bautista-Gili ◽  
Blanca Sanchez ◽  
Lucia Garcia ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Selection Bias ◽  
International Prognostic Index ◽  
B Cell Lymphoma ◽  
Stage Iii ◽  
Prognostic Impact ◽  
Differential Impact ◽  
Bulky Disease ◽  
Time Period ◽  
The Impact

Abstract Introduction: DLBCL is the more common non Hodgkin lymphoma. This is an aggressive lymphoma that is treated with a standard chemotherapy regimen: R-CHOP. In the last years attempts have been done to improve the outcome both increasing dose-density (CHOP14) or intensity (CHOEP, ACVBP, autologous stem cell transplantation) without obtaining benefit in terms of survival. This has allowed setting R-CHOP administered every 21 days (R-CHOP21) as the standard treatment for DLBCL patients. RDI is an important issue to consider when treating malignancies. Although this a well-known prognostic factor in Hodgkin lymphoma, scarce information has been published in DLBCL. Objective: The purpose of this study is further analyzing the prognostic impact of RDI in two cohorts of DLBCL patients treated with R-CHOP21 or R-CHOP14, to evaluate its differential impact when increasing dose density. Material and methods: All patients diagnosed of DLBCL from January-1999 to June-2013 at University Hospital Son Espases were retrospectively identified from Pathology Department registry to avoid selection bias. Only patients treated with R-CHOP21 or R-CHOP14 +/- radiotherapy were included (N=115). To increase the R-CHOP14 cohort we added also all patients treated with R-CHOP14 in the same time period in two additional hospitals (Hospital Son Llatzer of Palma and Hospital del Mar of Barcelona) identified from their Pharmacy registries to avoid selection bias (N=42). Other regimes, consolidations or maintenance were excluded. Table 1 shows main characteristics of the global series (N=157). RDI represents the ratio of the amount of a drug actually administered to the amount planned for a fixed time period. RDI was calculated as previously described. Briefly, RDI of each drug was obtained followed by an average of RDI in CHOP consisting in the sume of RDI of the 3 drugs divided by 3. Main prognostic factors at diagnosis in DLBCL were obtained, including international prognostic index (IPI) factors. Evaluations were carried out following standard guidelines. Results: Overall response and complete response rates were similar in both groups:86% and 76% for R-CHOP21 and 94% and 74% for R-CHOP14(p=0.17 and p=0.85, respectively). Median follow-up for alive patients was 68 months (4-156). There were no differences between the two cohorts in terms of either OS or PFS (Figure 1). In the R-CHOP21, both a reduction higher than 15% in RDI [RR 7.41 (2.51-21.83); (p<0.001)] and an unfavorable R-IPI [RR 2.99 (1.1-8.16); (p=0.032) were independently associated with a worse OS. For PFS only a reduction higher than 15% in RDI [RR 4.41 (1.77-10.99) (p=0.001) was independently associated to worse PFS. By contrast, in the R-CHOP14 group an unfavourable NCCN-IPI [RR 8.74 (2.23-34.25); (p=0.002)] and the presence of B-symptoms [RR 5.13 (1.98-13.3); p=0.001)] was independently associated to worse OS and having a AA stage III-IV [RR 5.09 (1.14-22.62); p=0.032)] and bulky disease [RR 3.95 (1.46-10.7); p=0.007)] were independently related to worse PFS. RDI reductions did not show any significant impact in OS or PFS in patients treated with R-CHOP14 (Figure 2). Conclusions: Overall in our series there were no differences in terms of response or survival between patients treated with R-CHOP21 or R-CHOP14. A higher rate of RDI reduction was observed in the R-CHOP14 group. However, the impact of RDI reductions on response and survival was only observed in the R-CHOP21 group but not in patients treated with R-CHOP14. We can conclude that R-CHOP21 and R-CHOP14 are equivalent regimens in terms of response and survival only if RDI reductions are avoided. For patients receiving R-CHOP21 we recommend using clinical and support measures in order to avoid RDI reductions. Table 1. Main clinical characteristics of the patients. R-CHOP21 group(n=74) R-CHOP14 group(n=83) P Age (median & range) 65 (25-88) 55 (15-79) 0.005 Sex (M/F) 34 (46%) / 40 (54%) 51 (61%) / 32 (39%) 0.056 ECOG PS > 1 17 (23%) 18 (22%) 0.85 Ann Arbor stage III-IV 40 (54%) 48 (58%) 0.75 B-symptoms 25 (34%) 26 (31%) 0.86 Elevated LDH 33 (46%) 40 (49%) 0.75 > 1 extranodal site 8 (11%) 19 (23%) 0.057 Bulky disease 23 (31%) 34 (41%) 0.24 R-IPI unfavorable 24 (32%) 26 (32%) 1 NCCN-IPI: - Low - Low-intermediate - High-intermediate - High 9 (13%) 27 (39%) 26 (38%) 7 (10%) 17 (21%) 35 (44%) 24 (30%) 4 (5%) 0.31 Elevated Beta-2-microglobulin 32 (49%) 31 (39%) 0.24 Radiotherapy 27 (36%) 27 (32%) 0.62 Figure 1. Figure 1. Figure 2. Figure 2. Disclosures No relevant conflicts of interest to declare.

The Impact of Cigarette Smoking On Overall Survival in Non-Hodgkin Lymphoma

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 5100-5100
Author(s):  
Nicholas J. Ollberding ◽  
Andrew M. Evens ◽  
Briseis Aschebrook-Kilfoy ◽  
Donne Bennett D. Caces ◽  
Dennis D Weisenburger ◽  
...  
Keyword(s):  
Overall Survival ◽  
Cigarette Smoking ◽  
Hodgkin Lymphoma ◽  
Conflicts Of Interest ◽  
B Cell Lymphoma ◽  
Prognostic Impact ◽  
Daily Number ◽  
Non Hodgkin Lymphoma ◽  
Former Smokers ◽  
The Impact

Abstract Abstract 5100 Introduction: Smoking has been suggested as a potential risk factor for the development of non-Hodgkin lymphoma (NHL). However, the prognostic impact of smoking in patients with NHL has not been well studied and may have important implications regarding outcome. Methods: In a population-based cohort of 308 NHL patients diagnosed between 1999 and 2002, we examined the association between cigarette smoking habits prior to NHL diagnosis and overall survival (OS). Multivariable Cox proportional hazards models adjusted for age, gender, and education were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for all NHL, and for follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL). Measurements of smoking included categories for smoking status, pack-years of smoking, years of smoking, daily number of cigarettes smoked, and years since quitting smoking. Continuous exposures for cigarette smoking were also examined with potential non-linear relations tested using restricted cubic splines. We conducted subgroup analyses adjusting for established clinical and prognostic variables. Results: In the patient cohort, a total of 96 deaths occurred over a median follow-up period of 8. 2 years. For all NHL cases, current smokers had worse survival (HR=1. 8 [1. 0–3. 1], ptrend=0. 07, for risk of all-cause mortality) when compared to never smokers. The inferior survival was also associated with pack-years of smoking (HR=1. 5 [0. 9–2. 4], ptrend=0. 12, for >30 pack-years) and smoking duration (HR=1. 5 [0. 9–2. 3], ptrend=0. 13, for >30 years). Smoking remained an independent predictor of OS after adjustment for initial treatment, stage at diagnosis and the presence of B symptoms: HR=2. 6 [1. 1–6. 3], ptrend=0. 03, for current smokers; HR=2. 4 [1. 1–5. 6], ptrend=0. 03, for patients with >30 pack-years of cigarette smoking; and HR=2. 5 [1. 2–5. 5], ptrend=0. 02, for patients smoking longer than 30 years. Among former smokers, a shorter interval from quitting to diagnosis was associated with worse survival (per 5 years of quitting cigarette smoking, HR=0. 9 [0. 8–1. 0], ptrend=0. 06). The associations with cigarette smoking and OS were stronger for FL than for DLBCL. In analyses stratified by age at diagnosis, the associations for current smokers (HR=3. 7 [1. 5–9. 2], ptrend=0. 01), daily number of cigarettes smoked (HR=2. 8 [1. 0–7. 5], ptrend=0. 04), and years of cigarette smoking (HR=3. 0 [1. 1–8. 3], ptrend=0. 04) were stronger for patients diagnosed at <60 years of age. The risk estimates for smoking with OS did not depart from unity among those diagnosed at ≥ 60 years of age. The associations between cigarette smoking and OS were similar for men and women. Conclusion: Our data suggest that cigarette smoking prior to diagnosis is associated with inferior OS in NHL patients. The reduction in survival is most prominent for patients diagnosed at <60 years of age and for those with FL. Among former smokers, greater time from cessation of smoking to diagnosis may improve OS. Further research examining the impact of smoking cession on OS among NHL patients is warranted. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Epigenetic Regulation of miR-92a and TET2 and Their Association in Non-Hodgkin Lymphoma

2021 ◽  
Vol 12 ◽  
Author(s):  
Esther K. Elliott ◽  
Lloyd N. Hopkins ◽  
Robert Hensen ◽  
Heidi G. Sutherland ◽  
Larisa M. Haupt ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Cell Lines ◽  
Target Genes ◽  
Cpg Islands ◽  
Mature Mirnas ◽  
Tumour Suppressor Genes ◽  
Promoter Regions ◽  
Aberrant Expression ◽  
Non Hodgkin Lymphoma

MicroRNAs (miRNAs) are well known for their ability to regulate the expression of specific target genes through degradation or inhibition of translation of the target mRNA. In various cancers, miRNAs regulate gene expression by altering the epigenetic status of candidate genes that are implicated in various difficult to treat haematological malignancies such as non-Hodgkin lymphoma by acting as either oncogenes or tumour suppressor genes. Cellular and circulating miRNA biomarkers could also be directly utilised as disease markers for diagnosis and monitoring of non-Hodgkin lymphoma (NHL); however, the role of DNA methylation in miRNA expression regulation in NHL requires further scientific inquiry. In this study, we investigated the methylation levels of CpGs in CpG islands spanning the promoter regions of the miR-17–92 cluster host gene and the TET2 gene and correlated them with the expression levels of TET2 mRNA and miR-92a-3p and miR-92a-5p mature miRNAs in NHL cell lines, tumour samples, and the whole blood gDNA of an NHL case control cohort. Increased expression of both miR-92a-3p and miR-92a-5p and aberrant expression of TET2 was observed in NHL cell lines and tumour tissues, as well as disparate levels of dysfunctional promoter CGI methylation. Both miR-92a and TET2 may play a concerted role in NHL malignancy and disease pathogenesis.

scholarly journals Cancer Risk After Bariatric Surgery in a Cohort Study from the Five Nordic Countries

2020 ◽  
Vol 30 (10) ◽  
pp. 3761-3767
Author(s):  
Wenjing Tao ◽  
Giola Santoni ◽  
My von Euler-Chelpin ◽  
Rickard Ljung ◽  
Elsebeth Lynge ◽  
...  
Keyword(s):  
Bariatric Surgery ◽  
Endometrial Cancer ◽  
Cohort Study ◽  
Cancer Risk ◽  
Hodgkin Lymphoma ◽  
Cox Regression ◽  
Nordic Countries ◽  
Chronic Obstructive ◽  
Non Hodgkin Lymphoma ◽  
The Impact

Abstract Purpose Obesity increases the risk of several cancers, but the influence of bariatric surgery on the risk of individual obesity-related cancers is unclear. This study aimed to assess the impact of bariatric surgery on cancer risk in a multi-national setting. Materials and Methods This cohort study included all adults with an obesity diagnosis identified from national patient registries in all Nordic countries (Denmark, Finland, Iceland, Norway and Sweden) from 1980 to 2012. Cancer risk in bariatric surgery patients was compared with non-operated patients with obesity. Multivariable Cox regression provided adjusted hazard ratios (HRs) with 95% confidence intervals (CIs). Age, sex, calendar year, country, length of follow-up, diabetes, chronic obstructive pulmonary disease and alcohol-related diseases were evaluated as confounders. Results Among 482,572 participants with obesity, 49,096 underwent bariatric surgery. Bariatric surgery was followed by a decreased overall cancer risk in women (HR 0.86, 95% CI 0.80–0.92), but not in men (HR 0.98, 95% CI 0.95–1.01). The risk reduction was observed only within the first five post-operative years. Among specific tumours, HRs decreased for breast cancer (HR 0.81, 95% CI 0.69–0.95), endometrial cancer (HR 0.69, 95% CI 0.56–0.84) and non-Hodgkin lymphoma (HR 0.64, 95% CI 0.42–0.97) in female bariatric surgery patients, while the risk of kidney cancer increased in both sexes (HR 1.44, 95% CI 1.13–1.84). Conclusion Bariatric surgery may decrease overall cancer risk in women within the first five years after surgery. This decrease may be explained by a decreased risk of breast and endometrial cancer and non-Hodgkin lymphoma in women.

scholarly journals Impact of Pharmacy Benefit Managers on Oncology Practices and Patients

2020 ◽  
Vol 16 (5) ◽  
pp. 276-284 ◽  
Author(s):  
Trevor J. Royce ◽  
Caroline Schenkel ◽  
Kelsey Kirkwood ◽  
Laura Levit ◽  
Kathryn Levit ◽  
...  
Keyword(s):  
Prescription Drug ◽  
Prescription Drugs ◽  
Business Practices ◽  
Pharmacy Benefit ◽  
Drug Benefits ◽  
Quality Cancer Care ◽  
Number Of Patients ◽  
Oncology Care ◽  
The Impact

Pharmacy benefit managers (PBMs) are thoroughly integrated into the drug supply chain as administrators of prescription drug benefits for private insurers, self-insuring business, and government health plans. As the role of PBMs has expanded, their opaque business practices and impact on drug prices have come under increasing scrutiny. PBMs are particularly influential in oncology care because prescription drugs play a major role in the treatment of most cancers and an increasing number of patients with cancer are treated with oral oncology agents managed by PBMs. There is concern that some PBM practices may threaten access to high-quality cancer care and may increase the financial and administrative burden on patients and practices. In this article, we review the role of PBMs in prescription drug coverage and reimbursement, discuss the impact of PBMs on oncology care, and present data from the 2018 ASCO Practice Survey assessing the knowledge and attitude of oncology practices toward PBMs.

The impact of hepatitis B virus infection and vaccination on the development of non-Hodgkin lymphoma

2017 ◽  
Vol 24 (10) ◽  
pp. 885-894 ◽  
Author(s):  
C.-E. Huang ◽  
Y.-H. Yang ◽  
Y.-Y. Chen ◽  
J.-J. Chang ◽  
K.-J. Chen ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Virus Infection ◽  
Hepatitis B ◽  
Hodgkin Lymphoma ◽  
Hepatitis B Virus Infection ◽  
Non Hodgkin Lymphoma ◽  
B Virus ◽  
The Impact

scholarly journals BMI-1 and survivin expression with clinicopathological correlation and prognostic impact in B and T/NK- cell non-Hodgkin lymphoma

2019 ◽  
Vol 9 (2) ◽  
pp. 11
Author(s):  
Nahed Ahmed Soliman ◽  
Lamia M Abdalkader ◽  
Doaa Shams
Keyword(s):  
Overall Survival ◽  
Hodgkin Lymphoma ◽  
Nk Cell ◽  
Survivin Expression ◽  
Polycomb Group ◽  
Clinicopathological Parameters ◽  
Prognostic Impact ◽  
Non Hodgkin Lymphoma ◽  
Significant Difference ◽  
Well Correlation

Background: The pathogenesis of non-Hodgkin lymphoma is a complex process that involves several molecular changes. Alterations in polycomb group proteins as well as Survivin have been described but details are still lacking particularly in T/NK-cell lymphomas. Polycomb proteins have a big role in cell cycle and differentiation. Survivin is another recently recognized player in non-Hodgkin lymphoma.Objective: To study the pattern of Bmi-1 and Survivin in different categories of B- and T/NK- cell non-Hodgkin lymphomas, their association with the clinicopathological parameters, and their impact on the prognosis of non-Hodgkin lymphomas.Material& methods: Immunohistochemical staining was used to study paraffin samples of 267 patients’ biopsies. We used tonsils and reactive lymph node as normal control.Results: Both Bmi-1 and Survivin showed significant upregulation in several subtypes B- (P = .000-.02 for Bmi-1 and .00- .03 forSurvivin) and T/NK cell lymphomas (P= .009-.03 for Bmi-1 and 0.008- 0.009 for Survivin) compared to normal tissue. Significantpositive correlation between Bmi-1 and Survivin was detected in both B- (Co= 0.539**, P = .00) and T - cell lymphomas (Co= 0.560**, P = .000). A statistically significant difference between overall survival and expression of both BMI-1 and Survivin was detected (P = .00 for BMI-1and survivin).Conclusion: Bmi-1 and Survivin show significant upregulation as well correlation with clinicopathological parameters and overall survival of non-Hodgkin lymphomas.

Sign in / Sign up

Export Citation Format

Share Document