scholarly journals Comparing the Outcome of Diffuse Large B-Cell Lymphoma in Very Elderly Patients (age greater than 80 years) with Elderly Patients (age between 65 to 79 years)

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5072-5072
Author(s):  
Charalampos S. Floudas ◽  
Ajay Dhakal ◽  
Sunjay Neupane ◽  
Pouyan Gohari ◽  
Abhinav B Chandra

Abstract Background Diffuse large B-cell lymphoma (DLBCL) is the most frequent NHL subtype and the risk for it increases with age. At the same time, in advanced countries, the population over 65 years old is increasing because of the continuous increase in life expectancy and as a result the incidence of DLBCL is increasing as well. Increasing age is a major determinant of therapeutic decisions since it is associated with the presence of concomitant diseases, however elderly (over 65 years old) and very elderly (>80 years old) patients are not often included in clinical trials. Consequently, the optimal management of patients in the very elderly has not been identified. We conducted a single-center retrospective study with the objective to compare the comorbidity profiles, chemotherapy offered and tolerance, as well as outcome between elderly and very elderly DLBCL patients. Method A chart review of patients diagnosed with DLBCL in our center from January 2008 to January 2014 identified 33 patients aged between 60 to 79 years (elderly group, EG) and 30 patients aged 80 or more (very elderly group, VEG). We analyzed the clinical and laboratory characteristics (gender, extranodal disease presence, International Prognostic Index (IPI) factors, ECOG performance status (PS), Charlson comorbidity index, B-symptoms, hemoglobin, serum albumin), Progression Free Survival (PFS) and Overall Survival (OS) in comparison between the two groups. Furthermore, we studied the percentage of patients that were offered chemotherapy in each group, the regimen that was offered and the completion of chemotherapy as planned. Results: Median age for the EG was 72 years and for the VEG was 84 years (80 - 93). Significant differences between EG and VEG were found in mean serum albumin concentration at diagnosis (3.48 vs. 2.77, p=0.008), ECOG PS (0.91 vs. 2.36, p=0.000), and International Prognostic Index (IPI) (1.76 vs. 2.54, p=0.023) between EG and VEG. Compared to EG, VEG patients were more likely to have comorbidities (100 vs. 81.8%, p=0.025) and extra-nodal disease (93.3% vs. 66.7%, p=0.012). Though there was no statistically significant difference in percent of patients receiving chemotherapy, greater percent of EG (60.6) received R-CHOP regimen compared to VEG (20.0, p=0.001). There was no significant difference in therapy related toxicity, but fewer patients in the VEG (60 vs. 90.5%, p=0.039) were able to complete the course of chemotherapy planned and fewer achieved CR (35.7% vs. 68.2, p=0.036). Median overall survival was 762 vs. 650 days (p=0.793) and median progression free survival was 704 vs. 331 days (p= 0.180) for EG versus VEG. Conclusion: Very elderly DLBCL patients may differ from elderly patients in ECOG PS, comorbidity profile and chemotherapy regimen. These patients were less likely to complete the course of chemotherapy and fewer achieved complete response compared to the elderly group. There were no statistically significant differences in outcomes between the two groups. Disclosures No relevant conflicts of interest to declare.

Blood ◽  
2005 ◽  
Vol 106 (10) ◽  
pp. 3383-3385 ◽  
Author(s):  
Craig H. Moskowitz ◽  
Andrew D. Zelenetz ◽  
Tarun Kewalramani ◽  
Paul Hamlin ◽  
Simone Lessac-Chenen ◽  
...  

AbstractA number of prognostic factors affect outcome in patients with relapsed or primary refractory diffuse large B-cell lymphoma (DLBCL), including refractory disease and the second-line age-adjusted international prognostic index. In de novo DLBCL, the cell of orgin, as determined by expression microarray analysis or immunohistochemistry (IHC), predicts event-free survival (EFS). We evaluated the cell of origin, as well as other pathologic markers of outcome, on the repeat biopsy specimen of 88 transplantation-eligible patients undergoing ifosfamide, carboplatin, etoposide (ICE) second-line chemotherapy (SLT) followed by high-dose therapy (HDT) and autologous stem cell transplantation (ASCT) to see if were they prognostic in the salvage setting. Pretreatment clinical factors were well balanced between the cohorts. There was no significant difference in response to SLT, HDT, event-free or overall survival based on the cell of origin or any of the common pathologic markers examined. The cell of origin as determined by IHC does not predict outcome in transplantation-eligible patients with relapsed or primary refractory DLBCL.


2003 ◽  
Vol 21 (8) ◽  
pp. 1459-1465 ◽  
Author(s):  
Luca Baldini ◽  
Maura Brugiatelli ◽  
Stefano Luminari ◽  
Marco Lombardo ◽  
Francesco Merli ◽  
...  

Purpose: To evaluate the effect of epirubicin on therapeutic response and survival in patients with indolent nonfollicular B-cell lymphomas (INFL) treated with pulsed high-dose chlorambucil. Patients and Methods: A total of 170 untreated patients with advanced/active INFL were randomly assigned to receive either eight cycles of high-dose chlorambucil (15 mg/m2/d) plus prednisone (100 mg/d) for 5 days (HD-CHL-P; arm A) or eight cycles of HD-CHL-P plus epirubicin 60 mg/m2 intravenous on day 1 (arm B). The responding patients were randomly assigned to either maintenance therapy with interferon alfa (IFNα-2a; 3 MU, three times weekly) for 12 months or observation. Results: There were 160 assessable patients (82 males, 78 females; median age, 63 years; range, 33 to 77 years); 77 patients were assigned to arm A, and 83 were assigned to arm B. Induction therapy led to 47 complete responses (CRs; 29.4%) and 68 partial responses (PRs; 42.5%), with no significant difference between the two arms (60 CR + PR in arm A [77.9%] and 55 CR + PR in arm B [66.3%]; P = .07). After a median follow-up of 38 months (range, 2 to 103 months), there was no between-group difference in overall survival (OS; P = .45), failure-free survival (P = .07), or progression-free survival (PFS; P = .5). Eighty-eight patients were randomly assigned to either IFNα-2a (n = 43) or observation (n = 45), without any difference in 3-year PFS (44% and 42%, respectively). Univariate analysis showed that OS was influenced by age, anemia, serum lactate dehydrogenase levels, and International Prognostic Index distribution; multivariate analysis identified age and anemia as having influence on OS. Conclusion: HD-CHL-P treatment outcome in INFL patients was good (50% 3-year PFS, minimal toxicity, and low costs); epirubicin did not add any advantage. One-year IFNα maintenance treatment did not prolong response duration.


Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2649-2649
Author(s):  
Honghui Huang ◽  
Fei Xiao ◽  
Fangyuan Chen ◽  
Ting Wang ◽  
Junmin Li ◽  
...  

Abstract Abstract 2649 Background: The International Prognostic Index (IPI) is a widely accepted prognostic factor system for diffuse large B cell lymphoma (DLBCL) patients treated with chemotherapy. However, the prognostic value of IPI has been a focal point of the debate in the era of immuno-chemotherapy. Recently, the study of British Columbia group suggested that a revised IPI (R-IPI) which redistributed the IPI factors into 3 distinct prognostic groups provided a more clinically useful prediction of outcome for patients with DLBCL. In order to reassess the value of IPI and R-IPI in unselected Chinese population, we conducted this study. Methods: A multicenter retrospective analysis of DLBCL patients treated with CHOP-like chemotherapy alone or plus rituximab was performed by Shanghai Lymphoma Research Group. In total, 438 patients of newly diagnosed DLBCL treated at 6 participated hospitals were included during the period of 1997–2008. The prognostic value of IPI and R-IPI at diagnosis with regards to overall survival (OS) and progression-free survival (PFS) was evaluated. Results: The median age at diagnosis was 50 years (range, 18–83 years), and the median follow-up was 34 months (range, 3–145 months). Among them, 241 patients received CHOP-like regimen, whereas 197 had rituximab (R)-CHOP-like regimen. While IPI remained predictive in CHOP-like group, it could not distinguish between each prognostic category in the R-CHOP-like group (Fig.1). Redistribution of the IPI factors into a R-IPI identified three distinct prognostic groups with significantly different outcomes both in the patients treated with and without rituximab. In R-CHOP-like arm, these three risk groups had distinctly different rates of 3-year progression-free survival rates of 96%, 84.3% and 67.5% (P<0.001), respectively, and 3-year overall survival rates of 96%, 87.6% and 71.1% (P<0.001), respectively (Fig.2). Conclusions: Our study underscores the power of R-IPI as a simplified and more clinically relevant predictor of the disease outcomes than the standard IPI in Chinese DLBCL populations in the rituximab era, and it deserves a further study in larger population-based prospective study. Disclosures: No relevant conflicts of interest to declare.


Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2971-2971
Author(s):  
Vijaya R. Bhatt ◽  
Fausto R. Loberiza ◽  
James O. Armitage ◽  
Timothy C. Greiner ◽  
Martin Bast ◽  
...  

Abstract Background: Prior studies have demonstrated unique clinicopathologic features of the BV of MCL including an inferior response to chemotherapy and poor long-term outcomes as compared to other MCL variants in the pre-rituximab era. A paucity of data precludes whether the use of rituximab or intensified therapy can overcome the inferior outcome associated with the BV. Methods MCL patients (n=169) treated by NLSG between 1983 and 2010 were included. Morphologic variants were classified based on published WHO criteria. We compared disease characteristics, therapy and outcomes according to MCL subtypes using the Kruskal Wallis or Chi-square tests. Univariate probabilities of progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan Meier method. Multivariate analyses were performed using Cox proportional hazards regression to evaluate differences in outcomes of MCL subtypes while adjusting for prognostic covariates. Results The study population included 19% BV, 37% diffuse and 44% nodular subtypes. BV, diffuse and nodular subtypes differed in the median age (61 vs. 68 vs. 59, p=.002) and stage III/IV disease (81% vs. 79% vs. 93%, p=.05) at diagnosis, but did not differ in the distribution of sex, Karnofsky performance status (KPS), MCL international prognostic index (MIPI), lactate dehydrogenase (LDH) level, B-symptoms, or extranodal involvement. Patients received the following therapies: intensified therapy such as Cyclophosphamide, Vincristine, Doxorubicin, and Dexamethasone (Hyper-CVAD) +/- Rituximab (R) (30%), Cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)-R-like (24%), CHOP-like (35%) or others (11%). Approximately one-third received autologous (25%) or allogeneic (8%) SCT. There was a significant difference in the type of chemotherapy given in each group (p=.002) but not in the use of radiation therapy or proportion in each group receiving autologous/allogeneic stem cell transplant (SCT). Median follow-up across MCL subtypes was similar. Overall response rate was similar for BV, diffuse and nodular subtypes (68% vs. 65% vs. 80%, p=.44). The 5-year progression-free survival for BV vs. diffuse vs. nodular was 16% vs. 22% vs. 31%; p=.06, (Figure 1) and 5-year OS was 24% vs. 32% vs. 56% respectively; p=.005, (Figure 2). In multivariate analysis, compared to BV, diffuse subtype had similar risk of disease progression or death (hazard ratio, HR of 0.78, 95% confidence interval (CI) of 0.48-1.26) whereas nodular subtype had lower risk (HR 0.62, 95% CI 0.39-0.99). Additionally, low or intermediate MIPI, good KPS, absence of B-symptoms and undergoing SCT were associated with lower risk of progression or death. A subset univariate analysis of BV demonstrated no survivors beyond 5 years after conventional chemotherapy, whereas 33% remained alive at 10 years after intensified therapy. Conclusions BV and nodular MCL presented at a somewhat younger median age compared to diffuse MCL, and BV and diffuse MCL was more likely to present as stage I/II disease, compared to nodular MCL. The PFS and OS of BV MCL are similar to diffuse MCL but OS is worse than nodular MCL. The use of SCT may improve survival in MCL including BV variant. Figure 1. PFS of different subtypes of MCL Figure 1. PFS of different subtypes of MCL Figure 2. OS of different subtypes of MCL Figure 2. OS of different subtypes of MCL Disclosures Armitage: Ziopharm Oncology: Consultancy; GlaxoSmithKline: Consultancy; Spectrum Pharmaceuticals: Consultancy; Roche: Consultancy; Tesaro bio Inc: Membership on an entity's Board of Directors or advisory committees.


2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 8552-8552
Author(s):  
Kevin A. Hay ◽  
Benny Lee ◽  
Ozge Goktepe ◽  
Joseph M. Connors ◽  
Laurie Helen Sehn ◽  
...  

8552 Background: DLBCL is potentially curable with combination chemotherapy such as CHOP-R. Although it is generally regarded appropriate to start chemotherapy promptly after diagnosis, the impact of the time from diagnosis to treatment initiation on treatment outcome is unknown. Methods: Patients diagnosed with DLBCL and treated with at least one cycle of CHOP-R with curative intent during 2003 – 2008 in British Columbia were identified in the Lymphoid Cancer Database. Additional demographic data were obtained from the BC Cancer Registry. The BC Cancer Agency provincial pharmacy database was used to obtain dates of chemotherapy administration. The impact of the time interval from the date of pathologic diagnosis to treatment on overall survival (OS) and progression-free survival (PFS) was evaluated. Results: A total of 793 patients were identified: 199 (25%) received CHOP-R <2 weeks after diagnosis, 244 (31%) at 2-4 weeks, 293 (37%) at 5-8 weeks, and 57 (7%) at >8 weeks. High international prognostic index, primary mediastinal DLBCL, and hospitalization at the time of CHOP-R start were associated with earlier initiation of chemotherapy (p<0.001 for all factors). Distance to chemotherapy from home (p=0.237), rural vs. urban location (p=0.952), geographic region (p=0.458), and median household income (p=0.127) were not associated to treatment start. Five-year PFS and OS respectively were 54% (SD 4%) and 61% (SD 4%) for treatment <2 weeks, 63% (SD 3%) and 66% (SD 3%) for 2-4 weeks, 70% (SD 3%) and 74% (SD 3%) for 5-8 weeks, and 60% (SD 7%) and for 61% (SD 8%) >8 weeks, p=0.006 (PFS) and p=0.024 (OS). A multivariate analysis demonstrated no significant difference between the groups. Conclusions: In a publicly funded healthcare system, earlier initiation of chemotherapy was strongly associated with poor prognostic factors, as well as inferior PFS and OS. The timing of chemotherapy initiation appears to be related to clinical factors instead of system or socioeconomic barriers. Notwithstanding the lack of detrimental outcomes in those commencing CHOP-R after 8 weeks, clinicians should endeavor to initiate curative chemotherapy as soon as possible after a diagnosis of DLBCL is established.


Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3429
Author(s):  
Bettina Wagner ◽  
Ulrich Dührsen ◽  
Andreas Hüttmann ◽  
Holger Nückel ◽  
Rafael Tomoya Michita ◽  
...  

Aggressive B-cell lymphomas account for the majority of non-Hodgkin lymphomas (B-NHL). NK cells govern the responses to anti-CD20 monoclonal antibodies and have emerged as attractive targets for immunotherapy in subtypes of B-NHL. NKG2C and its cognate ligand HLA-E represent key molecules for fine-tuning of NK cell-mediated immune responses. Here, we investigated the impact of genetic variants of NKG2C and HLA-E on clinical outcomes of 441 B-NHL patients. Homozygous deletion of NKG2C (NKG2C−/−) was three-fold increased in patients compared to 192 healthy controls. Among studied patients, NKG2C−/− was more abundant in International Prognostic Index (IPI) high-risk patients compared to patients with a lower IPI (p = 0.013). Strikingly, NKG2C−/− was associated with a significantly reduced 2-year PFS (progression-free survival) (p = 0.0062) and represented an independent risk factor for 2-year PFS in multivariate analysis (p = 0.005). For HLA-E, the cognate ligand of NKG2C, the HLA-E*01:01 allele frequency was increased in B-NHL patients compared to controls (p = 0.033) and was associated with complete remission in univariate (p = 0.034) and multivariate (p = 0.018) analysis. Our data suggest that NKG2C and HLA-E genotyping is a promising tool for both defining risk groups of aggressive B-NHL and predicting response to immune therapeutic approaches.


2013 ◽  
Vol 66 (5) ◽  
pp. 420-425 ◽  
Author(s):  
Hyoeun Shim ◽  
Jae-Il Oh ◽  
Sang Hyuk Park ◽  
Seongsoo Jang ◽  
Chan-Jeoung Park ◽  
...  

BackgroundBone marrow involvement confers a poor prognosis in patients with diffuse, large, B-cell lymphoma (DLBCL). However, the prognostic significance of concordant and discordant bone marrow involvement in these cases differs. We analysed this further in patients treated with R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone) at a single institute.Design and MethodsThe cytomorphology of bone marrow involvement was evaluated in 632 patients who were diagnosed with DLBCL in primary tissues and had received R-CHOP therapy. Bone marrow trephine biopsies and clot sections were analysed, along with the immunohistochemical analysis of CD20, CD79a and CD3.ResultsBone marrow involvement was identified in 80 of our DLBCL patient subjects (12.7%). Of these, 32 (40%) showed discordant bone marrow involvement, and 48 (60%) showed concordant involvement. Kaplan–Meier survival analysis showed that progression-free survival and overall survival was poorer in the concordant group (p<0.001). Multivariate analysis, adjusted for the International Prognostic Index score, showed that concordant involvement was an independent predictor of progression-free survival (p<0.001) and overall survival (p=0.011). Discordant involvement was not a negative prognostic factor independent of the International Prognostic Index.ConclusionsPrognostication based on bone marrow involvement cytomorphology is a useful indicator of progression-free survival and overall survival, independent of the International Prognostic Index score, in DLBCL patients. Accurate staging based on morphology should thus be included in bone marrow examinations of such cases.


Author(s):  
Florian Zettl ◽  
Marita Ziepert ◽  
Bettina Altmann ◽  
Samira Zeynalova ◽  
Gerhard Held ◽  
...  

AbstractIn elderly patients (pts) with aggressive B cell lymphoma (aNHL), curative treatment often cannot be administered because of comorbidities and tolerability. We analyzed the influence of age in pts > 60 years receiving the R-CHOP-14 regimen within different prospective DSHNHL trials. Of the RICOVER-60 trial and CHOP-R-ESC trials, 1171 aNHL pts were included in this retrospective analysis of age-dependent event-free survival (EFS), progression-free survival (PFS), and overall survival (OS). All patients received prophylactic G-CSF, and anti-infective prophylaxis with amphotericin B mouth wash and oral fluorchinolone was optional. In the CHOP-R-ESC trials, prophylaxis was augmented to include mandatory continuous orally administered aciclovir and a pneumocystis prophylaxis with cotrimoxazole as well as oral fluorchinolones during neutropenia. The patient population was separated into 4 age groups (61–65 years, 66–70 years, 71–75 years, and 76–80 years). The results from the RICOVER-60 trial were subsequently confirmed in the following CHOP-R-ESC trials by a multivariate analysis adjusted for IPI factors and gender. Significant differences (p < 0.001) in EFS, PFS, and OS were seen between age groups (RICOVER-60). Hematotoxicity, infections, and TRM increased with age. TRM was significantly elevated in the age group 76–80 years. Therefore, this analysis shows that an age above 75 years defines an especially vulnerable patient population when being treated with chemoimmunotherapy for aNHL. Prophylactic anti-infective drugs are essential and clinically effective in reducing morbidity when treating elderly aNHL pts.


2020 ◽  
Vol 14 (9) ◽  
pp. 1222-1230 ◽  
Author(s):  
T Severyns ◽  
J Kirchgesner ◽  
J Lambert ◽  
C Thieblemont ◽  
A Amiot ◽  
...  

Abstract Background and Aims The prognosis of lymphoma that occurs in patients with inflammatory bowel disease [IBD] is poorly known. Methods A multicentre retrospective cohort analysis was done in seven French tertiary centres from 1999 to 2019. Only lymphoma occurring in patients with previous established diagnosis of IBD were analysed. The primary outcome was progression-free survival at 3 years. Results A total of 52 patients [male 65%, Crohn’s disease 79%, median age 48.3 years, median duration of IBD 10.1 years] were included, of whom 37 had been previously exposed to immunosuppressants and/or biologics for at least 3 months and 20 had primary intestinal lymphomas. The lymphoma histological types were: diffuse large B cell lymphomas [N = 17], Hodgkin lymphomas [N = 17], indolent B cell lymphomas [N = 12], and others including T cell lymphomas, mantle cell lymphomas, and unclassifiable B cell lymphoma [N = 6]. The median follow-up after lymphoma was 5.1 years (interquartile range [IQR] 4–7.8). Progression-free survival at 3 years was 85% in the overall population (95% confidence interval [CI] 75%–96%) with no significant difference between the exposed and unexposed group, 79% for patients exposed to immunosuppressants and/or biologics [95% CI 67%–94%], and 83% for patients diagnosed with primary intestinal lymphoma [95% CI 67%–100%]. No relapse of IBD has been observed during chemotherapy. The IBD relapse rate at the end of the last chemotherapy cycle was 23% at 3 years [95% CI 11%-39%] in the overall population. Conclusions In this large cohort, the prognosis for lymphomas occurring in IBD appears to be good and similar to what is expected, irrespective of the exposure to biologics and/or immunosuppressants.


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