The impact of age, Charlson comorbidity index, and performance status on treatment of elderly patients with diffuse large B cell lymphoma

2012 ◽  
Vol 91 (9) ◽  
pp. 1383-1391 ◽  
Author(s):  
Tung-Liang Lin ◽  
Ming-Chung Kuo ◽  
Lee-Yung Shih ◽  
Po Dunn ◽  
Po-Nan Wang ◽  
...  
Keyword(s):  
Elderly Patients ◽  
B Cell ◽  
Cell Lymphoma ◽  
Performance Status ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Comorbidity Index ◽  
And Performance ◽  
The Impact ◽  
Large B Cell

scholarly journals Management Strategies for Elderly Patients with Diffuse Large B-Cell Lymphoma

2012 ◽  
Vol 08 (01) ◽  
pp. 71
Author(s):  
Loretta J Nastoupil ◽  
Rajni Sinha ◽  
Christopher R Flowers ◽  
◽  
◽  
...  
Keyword(s):  
Elderly Patients ◽  
B Cell ◽  
Cell Lymphoma ◽  
Performance Status ◽  
B Cell Lymphoma ◽  
Future Research ◽  
Prognostic Features ◽  
Large B Cell Lymphoma ◽  
The Impact ◽  
Large B Cell

Diffuse large B-cell lymphoma (DLBCL) is the most commonly occurring form of lymphoma and most commonly presents in the sixth decade. Given the dramatic rise of the incidence of lymphoma since the late 1990s in patients who present over the age of 65, and the expected increase in the prevalence of DLBCL with the aging population, defining appropriately tailored modern therapy for elderly DLBCL patients is an increasingly important clinical concern. Moreover, age has been one of the most important adverse prognostic features, with numerous studies associating older age with inferior outcomes. Although it has been well established that B-cell diversity decreases with age, and that the loss of diversity can be associated with clonal expansion of B-cells, it remains unknown how this or other factors contribute to the pathogenesis and poor prognosis in elderly patients with DLBCL. Furthermore, elderly patients often have more comorbid illnesses, worse performance status, less hematologic reserve, and altered pharmacokinetics related to decreased metabolism and clearance of drugs. We examine the impact of these factors on therapeutic decision-making in patients with DLBCL and explore treatment alternatives for elderly individuals. Future research is needed not only to address treatment strategies but also to define the biologic heterogeneity between younger and older patients with DLBCL, so that more rational therapeutic approaches can be investigated.

scholarly journals Management Strategies for Elderly Patients with Diffuse Large B-Cell Lymphoma

2012 ◽  
Vol 08 (02) ◽  
pp. 123 ◽  
Author(s):  
Loretta J Nastoupil ◽  
Rajni Sinha ◽  
Christopher R Flowers ◽  
◽  
◽  
...  
Keyword(s):  
Elderly Patients ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Future Research ◽  
Ageing Population ◽  
Prognostic Features ◽  
Large B Cell Lymphoma ◽  
The Impact ◽  
Large B Cell

Diffuse large B-cell lymphoma (DLBCL) is the most commonly occurring form of lymphoma and most commonly presents in the sixth decade. Given the dramatic rise of the incidence of lymphoma since the late 1990s in patients who present over the age of 65, and the expected increase in the prevalence of DLBCL with the ageing population, defining appropriately tailored modern therapy for elderly DLBCL patients is an increasingly important clinical concern. Moreover, age has been one of the most important adverse prognostic features, with numerous studies associating older age with inferior outcomes. Although it has been well established that B-cell diversity decreases with age, and that the loss of diversity can be associated with clonal expansion of B-cells, it remains unknown how this or other factors contribute to the pathogenesis and poor prognosis in elderly patients with DLBCL. Furthermore, elderly patients often have more co-morbid illnesses, worse performance status, less haematologic reserve and altered pharmacokinetics related to decreased metabolism and clearance of drugs. We examine the impact of these factors on therapeutic decision-making in patients with DLBCL and explore treatment alternatives for elderly individuals. Future research is needed not only to address treatment strategies but also to define the biologic heterogeneity between younger and older patients with DLBCL, so that more rational therapeutic approaches can be investigated.

scholarly journals IPI, Comorbidity Index, Hospitalization for Treatment-Related Adverse Events Are Predictors for Outcome in Elderly Diffuse Large B Cell Lymphoma Patients

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1860-1860
Author(s):  
Caner Saygin ◽  
Xuefei Jia ◽  
Brian T. Hill ◽  
Robert M. Dean ◽  
Bhumika Patel ◽  
...  
Keyword(s):  
Adverse Events ◽  
B Cell ◽  
Cell Lymphoma ◽  
Performance Status ◽  
Age Groups ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Comorbidity Index ◽  
Dose Reductions ◽  
Large B Cell

Abstract Background: International Prognostic Index (IPI) has been used as the primary prognostic tool in diffuse large B cell lymphoma (DLBCL) for more than 20 years. Even though the disease is more common in older population, the impact of comorbidities, dose reductions, and treatment-related adverse events (AEs) on the outcome in elderly DLBCL patients has not been well established. In this study, we aimed to investigate the effect of IPI, clinicopathological features, Charlson Comorbidity Index (CCI), AEs and dose reductions on survival of DLBCL patients aged 60 years or above. Methods: We identified 910 DLBCL patients (pts) treated at Cleveland Clinic between 2004-2014 and this analysis includes 413 pts aged ≥60 years. Patient and disease characteristics and treatment data of pts who received at least one cycle of treatment were analyzed for prognostic significance. CCI was calculated, excluding lymphoma, and patients were divided into low CCI (CCI score of 0-2) or high CCI (≥3). For regression analysis, patients were grouped into good or poor risk based on IPI ≤ 2 vs 3-5. Results: Median age of our cohort was 69 years (range, 60-100), 55% were male, and 91% Caucasian. Pts were divided into 3 age groups; 60-69 yrs (N=217), 70-79 yrs (N=124) and >80 yrs (N=72). Most pts had advanced stage disease (59%), high IPI ≥3 (58%) good performance status (PS) ≤1 (74%), and no B symptoms (31%). 15% had high CCI (≥3) with a trend towards higher incidence in >80 yrs (p=0.05). Our cohort had predominantly germinal center (GC) DLBCL (60%) with low incidence of MYC translocation (28%) among the 89 pts tested. Only median BMI (28%, p=0.007) and performance status (≥2: 27%, p=<0.001) was statistically significant among the age grps. 85% were treated with R-CHOP, 2% received CHOP, and 3% received R-EPOCH. 70% experienced at least one clinically significant AE with infection (34%) and febrile neutropenia (31%) being common. 78% had dose reduced chemo with higher frequency seen in older pts (59% in >80 yrs) (p=<0.001). Overall response rate was 92% with 78% achieving CR and no difference among the groups. Median OS and PFS were 9.6 and 3.8 years respectively with an estimated 10 year OS and PFS of 50% and 30%. In the univariable analysis, IPI (OS: HR 1.7, p=<0.001; PFS: HR 1.39, p=<0.001), ECOG PS (OS: HR 2.94 p=<0.001; PFS: 2.29, p=<0.001), CCI (OS: HR 2.1, p=<0.001; PFS: HR 1.59, p=0.015), LDH ratio (OS:HR 1.53, p=0.008; PFS: HR 1.58, p=<0.001), chemotherapy dose reduction (OS: HR 1.64, p=0.016; PFS: HR 1.45, p=0.029), AE (OS: HR 1.78, p=0.17; PFS: 1.56 p=0.017), and hospitalization (OS: HR 4.01, p-=<0.001; PFS: HR 1.56, p=0.017) predicted inferior OS and PFS. On multivariable analysis, only IPI (HR 1.5, p<0.001), CCI (HR 2.1, p=<0.006) and hospitalization (HR 2.4, p=<0.004) were significant predictors of OS. In addition to CCI (HR 2.0 p=0.013) and hospitalization (HR 2.45 p=<0.001), B symptoms (HR 0.62, p=0.038) was also prognostic for PFS. Among the age groups, adverse risk factors for OS were IPI (HR 1.47, p=0.006) and CCI (HR 1.47, p=0.006) in 60-69 yrs, and hospitalization in 70-79 years (HR 3.42, p=0.009). None of these factors predicted survival in >80 yrs, although there was trend observed with IPI (p=0.058) and PS (0.052). Conclusion: In this single center large cohort of DLBCL pts, higher CCI and hospitalization for AE were significant predictors of decreased OS and PFS, especially in pts aged 60-69 years. Although IPI is predictive, a better prognostic model incorporating comorbidities and treatment toxicities may help to better risk stratify older DLBCL patients. Figure Figure. Disclosures Smith: Spectrum: Honoraria; Abbvie: Research Funding; Genentech: Honoraria; Celgene: Honoraria.

Median Absolute Lymphocyte Count Independently Predicts Survival of Elderly Patients with Diffuse Large B-Cell Lymphoma Treated with R-Chemotherapy: Analysis of 651 Patients Included In the Czech Lymphoma Project

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2882-2882
Author(s):  
Vit Prochazka ◽  
Marek Trneny ◽  
David Salek ◽  
David Belada ◽  
Tomas Kozak ◽  
...  
Keyword(s):  
Elderly Patients ◽  
B Cell ◽  
Lymphocyte Count ◽  
Cell Lymphoma ◽  
Performance Status ◽  
B Cell Lymphoma ◽  
Absolute Lymphocyte Count ◽  
Newly Diagnosed ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Abstract 2882 Absolute lymphocyte count (ALC) at time of diagnosis has been documented as an independent predictor of survival in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). The optimal cut-off values of ALC are still a matter of debate. An extensive analysis of the prognostic impact of ALC in the elderly population treated with rituximab has not yet been carried out. Thus, we assessed the prognostic significance of different ALCs in unselected, newly diagnosed elderly patients with DLBCL in the population of the Central European region (the Czech Lymphoma Project registry). We analyzed data of 651 patients with confirmed DLBCL older than 59 years. Those with CNS involvement were excluded. The median age at diagnosis was 69 years (range, 60–97); the Ann Arbor stages were as follows: I (16.5%), II (26.1%), III (15.9%), and IV (41.5%). The IPI scores were: low (L) 19.8%, low-intermediate (LI) 26.6%, intermediate-high (IH) 24.3%, and high (H) 29.3%. We analyzed the prognostic value of lymphopenia with 3 different cut-off values. Values of ALC < 1.0 × 109/L and ALC < 0.84 × 109/L were chosen according to the previously published data, the third value was the median ALC at diagnosis (ALC 1.35 × 109/L). ALC < 1.0 × 109/L was observed in 201 (31%) and ALC < 0.84 × 109/L in 159 (24%) patients. ALCs below predefined levels were associated with higher (IH, H) IPI scores: ALC < 0.84 × 109/L (78% vs 46%, p < 0.001), ALC < 1.0 × 109/L (77% vs 43%, p < 0.001), and ALC < 1.35 × 109/L (68% vs 38%, p < 0.001); advanced disease (stages III/IV): ALC < 0.84 × 109/L (72% vs 53%, p < 0.001), ALC < 1.0 × 109/L (72% vs 51%, p < 0.001), and ALC < 1.35 × 109/L (66% vs 48%, p < 0.001); and low performance status (ECOG ≥ 2): ALC < 0.84 × 109/L (52% vs 27%, p < 0.001), ALC < 1.0 × 109/L (50% vs 25%, p < 0.001), and ALC < 1.35 × 109/L (43% vs 22%, p < 0.001). In 85% of patients, treatment was initiated with an anthracycline-containing regimen (CHOP), i.e. only 15% of patients recieved a non-anthracycline-based regimen (COP). The median number of chemotherapy cycles was 6. Chemotherapy was combined with rituximab in all patients (a median of 6 doses). Generally, treatment response was assessed in 544 (83.6%) patients. Complete remission (CR) or unconfirmed CR was achieved in 79.8% and partial remission in 12.5% of patients, with 7.7% of patients being classified as having stable disease or disease progression. CR rates were significantly higher in patients with higher lymphocyte counts: ALC > 0.84 × 109/L (82% vs 71%, p = 0.006), ALC >1.0 × 109/L (83.1% vs 71.7%, p = 0.008), and ALC > 1.35 × 109/L (85% vs 75%, p = 0.027). The overall survival (OS) and event-free survival (EFS) rates were superior in all subgroups of patients with higher ALC levels. The 3-year OS rates stratified by lymphocyte count: ALC > 0.84 × 109/L (67% vs 51%, p = 0.0002), ALC > 1.0 × 109/L (67% vs 52%, p = 0.0017), and ALC > 1.35 × 109/L (71% vs 55%, p = 0.0001). The 3-year EFS rates stratified by lymphocyte count: ALC > 0.84 × 109/L (61% vs 44%, p = 0.0002), ALC > 1.0 × 109/L (62% vs 44%, p = 0.0002), and ALC > 1.35 × 109/L (66% vs 47%, p < 0.0001). Only ALC < 1.35 × 109/L was found to be an independent negative prognostic factor for the OS (RR = 1.53, p = 0.006) and EFS (RR = 1.43, p = 0.013) in a multivariate analysis when compared with the LDH level, clinical stage, performance status and age (above median). In summary, the data support the hypothesis that host innate immunity is critical in tumor growth control and is a limiting factor for the efficacy of immunochemotherapy in elderly patients with DLBCL. The optimal cut-off levels of ALC may be different in various populations. This fact should be taken into account when designing new ALC-based prognostic schemes. Disclosures: Prochazka: ROCHE: Honoraria. Pytlik:ROCHE: Honoraria.

scholarly journals Retrospective Study of the Optimal CHOP Dose for Elderly Patients with Diffuse Large B-Cell Lymphoma

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4211-4211
Author(s):  
Keiko Ono ◽  
Hideki Tsujimura ◽  
Akiyasu Satou ◽  
Xiaofei Wang ◽  
Takeaki Sugawara ◽  
...  
Keyword(s):  
High Risk ◽  
Elderly Patients ◽  
B Cell ◽  
Cell Lymphoma ◽  
Performance Status ◽  
Dose Intensity ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Large B Cell ◽  
Chop Therapy

Abstract Background: Diffuse large B-cell lymphoma (DLBCL) is the most common type of malignant lymphoma, and the number of elderly patients with DLBCL is increasing. While rituximab plus CHOP (R-CHOP) therapy is considered as the standard first-line treatment for DLBCL, elderly patients are often frail and unable to tolerate the standard dose of R-CHOP. Fifteen years ago, we conducted a prospective study to investigate optimal reduced doses of CHOP therapy for patients aged 65-79 years and those older than 79 years. We concluded that 5/6 (83%) and 7/12 (58%) doses of standard CHOP are effective and tolerable for these two age groups, respectively (Mori M, et al. Leuk Lymphoma. 2001;41:359-66). Since then, we have applied this strategy with the standard dose of rituximab. To evaluate the efficacy and tolerability of reduced R-CHOP therapy for elderly patients, we performed a retrospective analysis. Methods: We reviewed medical records of patients aged 65 years or older with newly diagnosed DLBCL, who underwent R-CHOP therapy from August 2010 to December 2013. Intravascular large B-cell lymphoma and primary central nervous system lymphoma were excluded from this study because R-CHOP therapy alone is not considered as standard for these diseases. We calculated the relative dose intensity (RDI), dividing the actually used doses of cyclophosphamide and doxorubicin by the interval between each course compared with the standard doses (750 mg/m2 cyclophosphamide and 50 mg/m2 doxorubicin every 21 days). Results: During the study period, data were collected from 100 patients (56 males and 44 females) with a median age of 74 (65-86) years. Sixty patients had advanced stages, 40 patients had a score of at least one in the Charlson comorbidity index (Charlson ME, et al. J Chronic Dis. 1987;40:373-83), 18 patients had a poor performance status (Eastern Cooperative Oncology Group performance status: ≥2), and 14 patients were older than 79 years. The overall response rate was 93%, and the complete response (CR) rate was 81%. Three-year overall survival (3-yr OS) was 78%. In comparison with the international prognostic index (IPI), 3-yr OS was 100% (IPI: low, n=26), 94% (IPI: low-intermediate, n=17), 71% (IPI: high-intermediate, n=24), and 58% (IPI: high, n=33). Hematologically adverse events were generally tolerable. No patient experienced a grade 4 hemoglobin decrease, and only four patients experienced a grade 4 platelet decrease. Although 55 patients received granulocyte colony-stimulating factor, a grade 4 leukocyte decrease was common (n=38) and febrile neutropenia (FN) was often seen (n=21). Patients who experienced FN had a significantly shorter OS (p=0.04). With a median follow up of 44.4 months, 20 patients experienced disease progression and 15 patients died after progression. Five patients remained in CR but died of other types of cancer. The other seven patients died of other causes. The median RDI was 0.81 in patients aged 65-79 years and 0.58 in patients older than 79 years. These doses were very similar to the originally intended doses of 5/6 (0.83) for younger patients and 7/12 (0.58) for older patients. The older group tended to show shorter OS (3-yr OS: 64%). However, recurrence rates of the two groups were very similar. Conclusions: This study demonstrates that rituximab plus 5/6 or 7/12 doses of CHOP therapy are effective and tolerable for elderly patients aged 65-79 years and those older than 79 years, respectively. It is noteworthy that the prognosis of patients with an IPI score of ≤2 was very satisfactory. Based on these results, the dose intensity does not have to be increased for these low risk groups. It is possible that increasing the dose intensity in high risk (IPI score: ≥3) patients improves the outcome. However, high risk patients tend to have much tumor burden and a poor performance status. In this group, higher dose chemotherapy will also increase the risk of developing FN and might be associated with inferior OS. Treatment of frail elderly patients with high-risk DLBCL is extremely challenging, and we need to gain further experience. Disclosures No relevant conflicts of interest to declare.

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