Elderly non-Hodgkin Lymphoma Patients Research Articles

Non-Hodgkin Lymphoma Mortality in the Elderly Population By Race, Gender, and Region in the United States

Background: Over the past decades, non-Hodgkin lymphoma (NHL) patients have significant improvement in the 5-year relative survival rate. In elderly NHL patients, comorbidities play a major role in mortality. Studies have shown that lower survival rates are multifactorial and strongly associated with certain races, gender, socioeconomic status, and availability of rituximab. Therefore, we aim to assess the differences in causes of mortality among races and genders. To better understand environmental contributions to one-year survival rate in NHL patients state-wise in the US, we examined the mortality-to-incidence rate (MIR) in senior NHL patients characterized by race, gender, and American health ranking (AHR) index.Methods: This is a retrospective study using the Centers for Disease Control and Prevention database from 2008 to 2017. Patients ≥65 years with non-Hodgkin lymphoma were included. AHR assesses the nation's health on a state-by-state basis to determine state health rankings with a composite index of health measures. AHR consists of five weighted core measures (four groups of health determinants and one health outcome): (1). Behaviors including excessive drinking, obesity, smoking, (2). Community and environment including air pollution, poverty, infectious disease, violent crime, (3). Policy including immunization, public health funding, uninsured rate, (4). Clinical care including primary care physicians, mental health providers, preventable hospitalizations, and (5). Outcomes including cancer deaths, cardiovascular deaths, diabetes, disparity in mental status. A ten-year (2008-2017) average of all-determinants value from AHR were reported and MIR, a parameter that can serve as a proxy for survival, was compared between US states. We analyzed the association between NHL mortality and state health disparities using linear regression. Multiple-cause-of-death data is based on death certificates for US residents. Each death certificate contains a single underlying cause of death, up to twenty additional multiple causes, and demographic data. We analyzed the multiple cause age-adjusted mortality rate in White males and females versus African American males and females. All data were analyzed using R version 4.0.5, with p-values <0.05 in two-sided t-tests to indicate statistical significance.Results: In this 10-year analysis, the mean age-adjusted mortality rate (AAMR) in Whites, African Americans, and all populations were 38.2, 21.4, and 36.7 per 1,000,000 population, respectively. Among all 50 states, Idaho had the highest AAMR for all populations (42.7/1,000,000) and Whites (43.1/1,000,000); Minnesota had the highest AAMR for African Americans (29/1,000,000). District of Columbia had the lowest AAMR for all populations (26.4/1,000,000); New Mexico had the lowest AAMR for Whites (30.6/1,000,000) and New York had the lowest AAMR for African Americans (Table 1). Our results demonstrated that elderly NHL patients in states with better health all-determinants index had significantly lower MIR in all populations (R 2=0.2654, p <0.001, Figure 1). The three lowest MIR states in the US were Florida (0.319), Connecticut (0.348), and New York (0.348) (Figure 2). Whites were more likely to have underlying comorbidities than African Americans, especially ischemic heart disease (Male: OR 87.16, 95% CI 74.23-102.34; Female: 26.10, 95% CI 22.01-30.94), congestive heart failure (Male: OR 53.31, 95% CI 45.35-62.66; Female: OR 25.98, 95% CI 22.25-30.34), and chronic obstructive pulmonary disease (Male: OR 54.55, 95% CI 45.27-65.73; Female: OR 45.98, 95% CI 36.48-57.95) (Table 2,3).Conclusions: States of better health index in terms of all determinants had lower MIR for elderly NHL patients in the US. Factors contributing to the difference in MIR possibly include variations in socioeconomic status, insurance coverage, and healthcare access. Our results highlight the need to focus on secondary prevention to decrease morbidities and health disparities in NHL patients. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Assessing Individual Comorbidities in Elderly Non-Hodgkin Lymphoma Patients Undergoing Autologous Stem Cell Transplant — Obesity Associated with Inferior Outcomes

Assessing Individual Comorbidities in Elderly Non-Hodgkin Lymphoma Patients Undergoing Autologous Stem Cell Transplant — Obesity Associated with Inferior Outcomes

A potential treatment option for elderly non-Hodgkin lymphoma patients with multiple comorbidities: Two case reports and literature review

Non-Hodgkin lymphoma (NHL) is a heterogeneous lymphoproliferative malignancy. More than half of the NHL cases occur in patients over 65 years of age. As elderly patients have a poor performance status and multiple comorbidities, the use of standard chemotherapy is often limited, leading to poor clinical outcomes and an increasing need for an alternate therapeutic modalities.A 73-year-old man was diagnosed with extranodal NK/T-cell lymphoma concurrently combined with recurrent gastric adenocarcinoma and metastatic prostate cancer. A 79-year-old woman was diagnosed with T-cell and B-cell dual-phenotype NHL on the right chest wall showing tumor thrombosis and multiple enlarged lymph nodes under chronic emphysema with extensive pleural calcification. Both elderly patients had multiple comorbidities and pathologically confirmed non-Hodgkin lymphoma. Both patients achieved tumor responses following anticancer treatment with Korean medicine (KM), suggesting that the extracts of Angelica gigas Nakai and Geopungtang are potential options for treating NHL in elderly patients with multiple comorbidities.Considering the clinical outcomes of KM treatment in the two elderly patients with NHL and multiple comorbidities, this study generates a research hypothesis for future prospective clinical studies in patients with NHL who are ineligible for conventional anticancer therapy.

Allogeneic transplantation in elderly patients \u226565 years with non-Hodgkin lymphoma: a time-trend analysis

Allogeneic hematopoietic cell transplantation (allo-HCT) is a curative therapy for relapsed/refractory and high-risk non-Hodgkin lymphoma (NHL). However, no large studies have evaluated allo-HCT utilization in elderly NHL patients (≥65 years). Using the CIBMTR registry, we report a time-trend analysis of 727 NHL patients (≥65 years) undergoing the first allo-HCT from 2000 to 2015 in the United States (US). Study cohorts were divided by time period: 2000–2005 (N = 76) vs. 2006–2010 (N = 238) vs. 2011–2015 (N = 413). Primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), relapse/progression (R/P), and non-relapse mortality (NRM). Median age at transplant, use of reduced-intensity conditioning, and graft source remained stable, while use of unrelated donors increased in the most current era. The 1-year probabilities of NRM from 2000 to 2005 vs. 2006–2010 vs. 2011–2015 were 24% vs. 19% vs. 21%, respectively (p = 0.67). Four-year probability of R/P was similar among the three cohorts: 48% (2000–2005), 40% (2006–2010), and 40% (2011–2015) (p = 0.39). The 4-year probabilities of PFS and OS (2000–2005 vs. 2006–2010 vs. 2011–2015) showed significantly improved outcomes in more recent time periods: 17% vs. 31% vs. 30% (p = 0.02) and 21% vs. 42% vs. 44% (p < 0.001), respectively. Utilization of allo-HCT increased in elderly NHL patients in the US since 2000 with improving survival outcomes.

Safety and Efficacy of R-CEEP (Rituximab, Cyclophosphamide, Epirubicin, Etoposide, Prednisolone) in Elderly or Unfit Patients with Diffuse Large B-Cell Lymphoma (DLBCL): A Retrospective Single-Centre Experience

Background DLBCL is the most common subtype of non-Hodgkin lymphoma in elderly patients (age ≥70). R-CHOP is the standard of care for upfront treatment of fit patients, but may not be tolerated in patients with advanced age and/or comorbidities. There is no established standard of care for this group of patients and dose reduction (R-miniCHOP) or avoidance/replacement of anthracyclines are common strategies, aiming to deliver tolerable immunochemotherapy and provide meaningful outcomes and potential cure. R-CEEP is a dose-reduced regimen that incorporates etoposide and an alternate anthracycline epirubicin. We describe our single-centre experience with R-CEEP for elderly (age ≥70) or unfit patients (CIRS-G &gt;6) with newly-diagnosed or relapsed DLBCL deemed unsuitable for R-CHOP. Method All patients receiving R-CEEP for a histological diagnosis of DLBCL at Royal Prince Alfred Hospital from 2000 to 2019 were retrospectively reviewed. R-CEEP (rituximab 375mg/m2 day 1, cyclophosphamide 300mg/m2 day 1, epirubicin 50mg/m2 day 1, etoposide 100mg/m2 day 1 and prednisolone 50mg daily for days 1-5) was delivered every 14 or 21 days at physician discretion planning for 6 cycles. GCSF and antimicrobial prophylaxis were used at physician discretion. The cardiac ejection fraction was assessed as satisfactory (&gt;50%) prior to commencement. Baseline demographics, R-IPI, co-morbidities as assessed by CIRS-G, treatment response and adverse events (AEs) were recorded. Results Data from 61 patients were reviewed; 54 received R-CEEP for de novo DLBCL and 7 for DLBCL with a background of previously-treated lymphoma (1 DLBCL; 6 low-grade NHL). The median age at diagnosis was 80 (range 34-93), with 79% aged 75 and 28% aged 85. Thirty-three patients (54%) were female; 87% had Ann Arbor stage III/IV and 52% had R-IPI 3-5. Median CIRS-G was 9 (range 2-20) with 74% of patients having CIRS-G &gt;6. GCSF prophylaxis was used in 67%. The median follow-up was 2.7 years (range 0.1-10.0 years). Overall response was 54/61 (89%), with complete response (CR) in 42 (69%), partial response (PR) in 12 (20%) and progressive disease (PD) in 1 (2%). Response was not assessed in 6 patients due to early treatment discontinuation for palliation or AEs (4), cerebral palsy (1) and loss to follow-up (1). In patients receiving R-CEEP as upfront therapy, CR was obtained in 38/54 (70%), PR in 10/54 (19%) and 6 were not assessed as above. In the 7 patients receiving R-CEEP as salvage therapy, 4 obtained CR, 2 PR and 1 had PD. Median PFS and OS for the total cohort were 5.2 and 9.4 years respectively; for de novo DLBCL patients, 7.1 and 9.4 years and for patients receiving salvage therapy, 1.1 and 2.0 years. There was no statistically significant difference in PFS or OS when comparing patients aged &lt;80 and ≥80, or with CIRS-G ≤6 and &gt;6, or CIRS-G ≤9 and &gt;9. Relapsed disease was identified in 19 patients (31%) during follow-up. Of the 75 AEs reported, grade 3/4 AEs accounted for 67%. Infective complications were the most frequent (53%; 40) and febrile neutropenia accounted for 8 AEs. Grade 3/4 haematological toxicity occurred in 19% (14). Despite this, the majority (43/61; 70%) received six cycles of R-CEEP. In the remaining 18 patients, 5 completed 6 cycles with dose-reduction and 13 patients discontinued therapy due to serious AEs (9), treatment intolerance (2) or patient preference (2). Of the 29 deaths recorded during the follow-up period, 18 were due to relapsed/progressive disease; 5 to infection (4 of these in CR, 0.5 to 9 years after the end of treatment, and 1 of urinary sepsis in a patient 3 months after early treatment discontinuation due to toxicity) and 6 to unrelated causes. Discussion We demonstrate that R-CEEP is an effective and deliverable immunochemotherapy in elderly or unfit patients with DLBCL. Furthermore, survival outcomes were not impacted by CIRS-G &gt;9 or age ≥80, illustrating efficacy and tolerability even in patients predicted to have a particularly poor prognosis. Our cohort outcomes are not inferior to those reported in elderly fit patients treated with other dose-reduced regimens including R-miniCHOP (Peyrade et al, Lancet Oncology 2011) and R-miniCEOP (with epirubicin; Merli et al, Leukemia and Lymphoma 2012). This data supports the use of R-CEEP as an alternative immunochemotherapy option for patients with DLBCL who may not be candidates for R-CHOP. Disclosures Iland: Celgene: Other: Speaker honorarium. Ho:La Jolla: Other: investigator meeting travel costs; Novartis: Other: investigator meeting travel costs; Janssen: Other: investigator meeting travel costs; Celgene: Other: investigator meeting travel costs.

Association between Lactate Dehydrogenase Levels to the Response of Non-Hodgkin Lymphoma in Elderly Patients Who Treated with First-Line Chemotherapy in Sanglah General Hospital.

BACKGROUND:Non-Hodgkin Lymphoma (NHL) is a malignant haematological disease originates in the lymphocytes, caused by an abnormality in lymphocytes development which forms a tumour and may become cancer. Chemotherapy is the main treatment modality for aggressive lymphoma, but only a few patients achieve remission. Several factors such as age, clinical stadium, number of extranodal regions, and Lactate Dehydrogenase (LDH) level played a role in determining response to chemotherapy.AIM:To measure the association between LDH levels to prognosis of NHL in elderly patients who treated with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone chemotherapy in Sanglah General Hospital.METHODS:This study used a retrospective descriptive study on elderly NHL patients in Sanglah General Hospital from January until December 2014. The evaluation was measured using the IPI score to determine the prognosis of patients. Demographic data, the stadium, extranodal region, LDH level, and response to chemotherapy were recorded.RESULTS:Twenty-five patients were included in the study. The age ranged was between 61-76 years old (Mean 65,68 ± 4,7 years; Median 65 years). The number of male patients was 19 (76%). Diffuse Large B-Cell Lymphoma (DLBCL) is the most common histopathological structure observed on the patients (68%). LDH levels were normal in 51.6% of the patients and considered high in the rests (48.4%). Results of the chemotherapy were a good response in 72.2%. Compared to the patients who showed complete response to chemotherapy, patients with no response (partial response and progression) had significantly higher levels of LDH (OR: 13,1; 95% CI: 1,36-126,30; p = 0,001).CONCLUSION:Non-Hodgkin Lymphoma in elderly patients with no response to chemotherapy had significantly higher levels of LDH than patients with complete response.

Abstract 4225: Myelodysplastic syndrome and acute myeloid leukemia following use of chemo-immunotherapy and granulocyte colony-stimulating factors among elderly non-Hodgkin lymphoma patients

Abstract Purpose The purpose of this study was to examine use of granulocyte colony-stimulating factors (G-CSF) in relation to risk of myelodysplastic syndrome and acute myeloid leukemia (MDS/AML) in a population-based cohort of elderly patients with non-Hodgkin lymphoma (NHL). Methods We conducted a retrospective cohort study of adults ages 66 years and older diagnosed with first primary NHL between 2001 and 2011 using the Surveillance Epidemiology and End Results (SEER)-Medicare linked database. Patients were included if they were alive and without documented secondary primary cancer at three months post-diagnosis. Using a validated algorithm with Medicare claims and SEER records, we identified MDS/AML cases, primary NHL treatment received (i.e., chemo-immunotherapy and radiation) and type and number of doses of G-CSF received (i.e., filgrastim and/or pegfilgrastim). We determined the risk of developing MDS/AML at 12 months or longer after NHL diagnosis. We estimated adjusted hazard ratios (HR) and 95% confidence intervals (CI) for MDS/AML risk associated with G-CSF use in cause-specific Cox proportional hazards models, stratified by treatment to account for confounding by indication. Results A total of 18,245 patients were included with a mean age of 76 years and median follow up of 3.5 years. Most patients were diagnosed with diffuse large B-cell lymphoma (34%) and follicular lymphoma (22%). Fifty-six percent of all patients received chemo-immunotherapy, among whom most received rituximab-based chemotherapy (74%) or monotherapy (18%). G-CSF was most commonly used among those who received rituximab plus chemotherapy (77%). Subsequent MDS/AML was observed in 666 (3.7%) patients. Overall, we found a modest increased risk of MDS/AML with any use of G-CSF (HR=1.28, 95% CI 1.01-1.62); although, a linear trend was observed with increasing number of G-CSF doses (P&amp;lt;0.001). Among patients receiving rituximab plus chemotherapy, risk of MDS/AML was highest in those receiving 10 or more G-CSF doses (HR=1.64, 95% CI 1.14-2.37). When analyzing specific G-CSF agents, this increased MDS/AML risk was consistently observed with filgrastim (10+ doses: HR=1.67, 95% CI 1.25-2.23), but not with pegfilgrastim (10+ doses: HR=1.11, 95% CI 0.84-1.45). Conclusions In this study of elderly NHL patients, we observed a higher MDS/AML risk among those receiving chemo-immunotherapy and G-CSF that was specific to higher number of filgrastim doses but not pegfilgrastim. The benefits of preventing complications from therapy-related neutropenia in patients receiving highly myeloablative treatments likely outweigh the risk of this rare but serious second primary cancer. Understanding differential risk by type of agent warrants further study with the increasing use of G-CSF and FDA-approved biosimilar products (filgrastim-sndz) newly available. Citation Format: Kellyn M. Moran, Zhaoju Wu, Sruthi Adimadhyam, Todd A. Lee, Brian C. Chiu, Gregory S. Calip. Myelodysplastic syndrome and acute myeloid leukemia following use of chemo-immunotherapy and granulocyte colony-stimulating factors among elderly non-Hodgkin lymphoma patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4225.

L-PROBe: A Novel Non-anthracycline Combination Chemotherapy Regimen for Aggressive B Cell Non-Hodgkin Lymphoma in Elderly Patients.

The management of aggressive B cell lymphomas in elderly patients is associated with poor tolerability of commonly used chemotherapeutic agents. The safety and tolerability of a novel combination chemotherapy regimen utilizing rituximab, lenalidomide, bendamustine, vincristine and prednisolone was assessed in a series of elderly patients with new onset or relapsed/refractory aggressive B cell lymphoma and inability to receive conventional chemotherapy due to poor performance status and/or significant comorbidities. Ten patients (7 male, 3 female) with a median age of 72years (range 58-79years) received therapy with lenalidomide (10mg/day on days 1-14), rituximab (375mg/m2 on day 1), bendamustine (90mg/m2 on days 1 and 2), vincristine (1.4mg/m2 on day 1) and prednisolone (60mg/m2/day on days 1-5) with cycles repeated every 28days. Grade 3/4 hematological toxicities included neutropenia (30%), anemia (30%) and thrombocytopenia (10%). An overall response rate of 40% was observed with a median survival of 120days (range 14-286days). Three of the patients who responded achieved complete remission at the end of six cycles of therapy. This combination chemotherapy appears to be well tolerated and effective in elderly patients with poor performance status. Larger controlled studies are indicated to clearly demonstrate applicability of this novel regimen.

Efficacy of Vindesine + Dexamethasone (VDS+Dexa.) in Elderly Patients with Relapsed or Refractory Malignant Lymphoma

Background; The number of non-Hodgkin's lymphoma (NHL) patients in the elderly has been increasing due to the long-lived society. It is not rare to treat elderly NHL patients aged over 85 years old. Individualizing the doses of cancer chemotherapy agents and progress in supportive therapy has improved the prognosis for elderly patients with NHL. Prolonged hospitalization elderly patients have adverse effects, which include dementia, difficulty in walking, and depression. Optimal treatment for these patients is unknown. Patients and Methods; In our hospital between April 2012 and December 2014, we treated 19 elderly patients (85 and over 85 years) with NHL as outpatients with VDS 3mg (day 1) and Dexa. (day 1-4) which repeated every 3 weeks for as long as possible. Results; Complete remission was achieved in 5 patients and partial remission in 6; the median duration of survival was 14 months. Adverse effects included leukopenia in 1 patient (<1,000 cells/μl), thrombocytopenia in 1patient (<5×104 cells/μl). Conclusion; VDS+Dexa. is useful in elderly patients because of its low hematological and non-hematological toxicity. These results indicate that VDS+Dexa. is effective and safe for the treatment of NHL in elderly patients. This outpatient chemotherapy caused no serious adverse reactions. DisclosuresNo relevant conflicts of interest to declare.

Safety and Efficacy of Autologous Hematopoietic Cell Transplantation for Elderly Patients with Lymphoma: Chemosensitive Disease Rather Than Age or Co-Morbidity Index Predicts Outcome

Introduction: High dose chemotherapy (HDT) and autologous hematopoietic cell transplantation (AHCT) are considered standard of care as first line therapy in mantle cell lymphoma (Dreyling et al., 2005; Geisler et al., 2012) and in first line refractory and chemosensitive relapse Non-Hodgkin Lymphoma (NHL) (Philip et al., 1995) . The development of hematopoietic cell transplant comorbidity index (HCT-CI) (Sorror et al., 2009) for recipient selection and transplant risk evaluation have impacted on patient selection. Over the last decade, most transplant program have seen an increase in the median age of AHCT recipients(McCarthy et al., 2013). Limited data are available to optimise elderly patients selection for transplantation while minimising the risk of treatment related toxicity and mortality (TRM). The goal of this study was to identify factors impacting the safety and efficacy of AHCT in the elderly NHL patients in order to better select those who will benefit from this intervention. Method: This is a single center, retrospective study examining outcomes of AHCT in elderly patients (≥60 years old) with NHL. Between January 1st, 2008 and January 1st, 2015, 90 patients met the inclusion criteria and were included in the study. Patients signed an informed consent and the ethics committee of our institution approved the study. Progression-free-survival (PFS) and overall survival (OS) were analyzed according to age at time of transplantation, HCT-CI, lymphoma histology and disease status at time of transplant. Toxicities were analyzed according to age and HCT-CI. Results: Median age at time of NHL diagnostic was 60 years (range 42 to 68) and 63 years at time of transplant (range 60 to 69). One third (33%) of our cohort was ≥65 years old. Histologic sub-type was mainly composed of follicular (36%), mantle cell (20%) and large B-cell lymphoma (38%). 50% of patients had high-risk disease and 31% had low risk disease. HCT-CI was low-risk in 34%, intermediate risk in 40% and high-risk disease in 26%. BEAM/BEAC conditioning regimen was used in 94%. The median graft CD34+/kg cell dose infused was 4.87. The median time to neutrophil engraftment was 10 days (range 8 to 14 days) and platelet recovery was 16 days (range 11 to 43 days). The incidence of febrile neutropenia was 92% with 2% admission to the intensive care unit (ICU) with no difference between patients younger or ≥65 years old. Our cohort received a median of 8 days of antibiotics (range 0 to 41 days). Absolute lymphocyte count &lt; 0,3 X 103 cells/uL at 14 days after transplant was associated with higher incidence of septic choc (p=0,024) and ICU admission (p=0,034). Age ≥65 year was not associated with an increase TRM and was surprisingly associated with less total parenteral nutrition (p=0,046) and narcotics uses (P=0,011). The median length of stay was 26 days. The median follow-up was 27 months (range, 1 to 87), median PFS of 46 months (Confidence Interval (CI); 95%, 24,4-67,6) (graph 1) and OS not reached (graph 2). The estimated 5 years OS is 62% and PFS is 40%. Transplant related mortality (TRM) was only 1% at 100 days and 2% at 1year after transplant. The only 2 patients who died from TRM died from cardiac arrest (1 month) and from an unknown cause (3 months). The 1-year progression rate was 30% (graph 3) and mortality rate only 12%. Progressive disease status following first line therapy was associated with a worse PFS compared to the achievement of a complete remission (Hazard Ratio (HR) 2,77; CI 95%, 1,18; 6,49). Progressive disease status at time of transplant was also associated with a lower PFS (HR 9,30: CI 95% 2,55 to 33,92) and OS (HR 13,44: CI 95% 2,68 to 67,48). HCT-CI score did not correlate with OS. International Prognostic Index (IPI), age and treatment type did not influence PFS or OS. Surprisingly, HCT-CI score did not correlate with toxicities, morbidity or mortality. Conclusion: In this single center retrospective study of elderly patients with NHL, AHCT was proven to be safe and effective. Progressive disease at the time of transplant was associated with worse PFS and OS. HCT-CI did not allow the categorization of patients in different prognostics group. Lymphocyte count at day 14 could identify patients at significant risk of complications. Our data suggest that age alone should not exclude patients from transplantation. However, HDT and AHCT should be reserved to chemosensitive patients and avoided in the elderly patient with progressive disease. Figure 1. Figure 1. Figure 2. Figure 2. Figure 3. Figure 3. Disclosures No relevant conflicts of interest to declare.

Oral Antimicrobial Drug Use during Chemotherapy in Medicare Enrollees with NHL

Introduction: Febrile neutropenia and hospitalizations for infection are serious potential complications of myelosuppressive chemotherapy treatment in cancer patients. Oral antimicrobial use may provide effective prophylaxis against these complications in the elderly population. The available literature provides a limited description of antimicrobial use in elderly patients with non-Hodgkin lymphoma (NHL) receiving chemotherapy.Objectives: Describe the use patterns of oral antimicrobial agents in elderly patients with NHL on chemotherapy.Methods: The study population included non-HMO enrollees in the 20% Medicare sample with Parts A, B, and D coverage who had NHL and initiated their first course of chemotherapy between July 1, 2007, and November 30, 2011. We searched Part D claims for oral antimicrobial agents from 5 days before chemotherapy initiation to the end of the first cycle. We examined type of antimicrobial agents prescribed and timing of first prescription fill relative to chemotherapy initiation. Counts and percentages were estimated.Results: The study cohort included 6306 patients with NHL; 1682 patients (26.7%) had at least one prescription fill for an oral antimicrobial agent during the first cycle, for an overall total of 2569 claims for antimicrobials. Of these, 77.1% were for antibacterial, 9.9% for antifungal, and 13.1% for antiviral agents. Of antibacterial claims, 44.3% were for fluoroquinolones, 16.2% for sulfonamides, 12.0% for penicillins, and 12.0% for cephalosporins. First prescription fill occurred in the 5 days before the start of the first cycle for 17.4% of patients, from day 0 (the beginning of the cycle) to day 5 for 22.9%, and from day 6 to the end of the cycle for 59.7%. Peak days for first prescription fill were days 0, 7, and 14 of the first chemotherapy cycle (Figure).Conclusions: Over 25% of elderly NHL patients filled prescriptions for oral antimicrobial agents during the first cycle of chemotherapy. Since these data represent the fill date and not the date a patient started taking the medicine, it is possible that all fills in the 5 days before day 0 were to be started on day 0. Under this assumption, about 26% of prescriptions were started at the beginning of the cycle, likely for prophylaxis, and the remaining (especially peaks on days 7 and 14) may reflect either prophylaxis or treatment for an active infection. The literature suggests that peak infection risk occurs between days 7 and 16 of the chemotherapy cycle. Current antibiotic use patterns may not be optimal for patient care. [Display omitted] Note: 114 patients had their first oral antimicrobial prescription fill after day 23, but these results could not be shown because there were fewer than 11 patients on each of those days. DisclosuresPage:Amgen Inc.: Employment, Equity Ownership. Barron:Amgen Inc.: Employment, Equity Ownership. Morrow:Amgen Inc.: Employment, Equity Ownership. Stryker:Amgen Inc.: Employment, Equity Ownership. Acquavella:Amgen Inc.: Employment, Equity Ownership. Collins:ZS Pharma Inc.: Consultancy; Keryx Biopharmaceuticals, Inc.: Consultancy; Amgen Inc.: Consultancy; NxStage Medical Inc.: Consultancy.

Experience of using rituximab for recurrent non-Hodgkin lymphoma in elderly patients of the Orel region

Experience of using rituximab for recurrent non-Hodgkin lymphoma in elderly patients of the Orel region

Early cytological diagnosis of extranodal stage I, primary thyroid Non-Hodgkin lymphoma in elderly patients. Report of two cases and review of the literature

BackgroundPrimary thyroid lymphomas (PTLs) account for 5% of thyroid malignant tumors and often develop in patients with Hashimoto Thyroiditis (HT). Fine-needle cytology (FNC) is widely used in the diagnosis of thyroid nodules, including those arising in HT. Two PTL cases in HT elderly patients are here described and discussed.MethodsFNC was performed in rapidly enlarged thyroid nodules of 2 elderly patients under ultrasound (US) control. FNC was used to prepare conventional cytologic smears, immunocytochemistry (ICC) and flow cytometry (FC) assessment of cell populations.ResultsThe above cases were diagnosed as well differentiated, small B-cell and diffuse large B-cell thyroid lymphomas, respectively, by means of FNC. The histological diagnoses were mucosa-associated non Hodgkin lymphoma (MALT) and diffuse large B-cell lymphoma (DLBCL), confirming FNC diagnoses, and patients were treated accordingly.ConclusionsFNC diagnosis of PTL is reliable and accurate; it may be conveniently used in the clinical practice since it provides indications for appropriate therapeutic procedures or diagnostic surgery, and avoids to treat benign nodules.

Outcome and treatment of 62 Patients Aged Over 75 Years with Low Grade Non Hodgkin Lymphoma

AbstractAbstract 4854The incidence of B cell Non Hodgkin Lymphoma (NHL) is steadily increasing with age and about 40% of cases occur in patients aged over 70 years. Some series have reported that low grade NHL lymphomas represent about 35% of all B NHL in elderly patients. However few data are available on the outcome of patients aged over 75 years. MethodsWe report in a retrospective study the outcome and management of 62 patients aged over 75 years and followed between Jan, 2006, and Jan, 2012 from 2 french centers (Amiens, Abbeville).The primary endpoint was overall survival (OS); secondary endpoints were response rates, progression free survival (PFS), and toxicity. Results62 patients were registered with median age of 80,4 years (75–92): 31 patients with follicular lymphomas (FL) and 31 other low grade LNH: 15 Marginal Zone Lymphomas (MZL) of witch 11/31 splenic MZL, 1 gastric MALT, 5 lymphoplasmocytic and 10 lymphocytic lymphomas.At diagnostic, evaluation included: computed tomography scan for 46/62 patients (76%), bone marrow biopsy: 17/62 (27%), abdominal echography for 13/62 (24%) patients, echocardiography 24/62 (39%) and positron emission tomography for 11/62 (17%) patients. Charlson score (0–27) was evaluable for all of them with a median score of 2(0–4).At analysis, the median follow up was 23 months (range 0–79). Median FLIPI was 3 (0–5) for FL and median IPI 3(0–5) for other NHL. 21/31 (68%) FL patients and 27/31 (87%) other NHL had stage III or IV in the Ann Arbor classification.47/62 (76%) patients received chemotherapy: 27/31 (89%) FL patients and 20/31 (65%) with other NHL. 12/62 (19%) patients were undergoing watchfull waiting (11 patients with other NHL, 1 FL); 1 patient refused chemotherapy; 1 FL patient died before any treatment. 29/47 (61%) treated patients received Rituximab (R).In the FL group, 12/31 (39%) received RCVP (C=Cyclophosphamide, V=Etoposide, P=Prednisone), 12/31 (39%) RCHOP-like regimen, 2/31 (6%) chlorambucil, 1/31 (3%) corticotherapy alone, 1/31 (3%) radiotherapy alone and 2/31 (6%) chemotherapy plus radiotherapy.For other low grade NHL, 2/31 (6%) received RCVP, 3/31 (9%) RCHOP-like regimen, 10/31 (32%) Chlorambucil, 1/31(1%) Fludarabine, 4/31(13%) orally cyclophosphamide and corticosteroid.17 on 47 treated patients (36%) were in complete remission: 10/27 (37%) FL and 7/20 (35%) other NHL.The 2-years OS was 67%: 61% in the FL group and 74% other NHL (difference not significative); the 2-years PFS was 68%: 60% for FL and 77% for other low grade NHL.In univariate analysis, OS was affected by IPI (p=0,02) and FLIPI (p=0,008) (figure), but not by serum albumin concentration ≤ 35g/L, lymphopenia ≤1G/L, or Charlson score.25 deaths were reported (14 FL and 11 other NHL): 9 lymphoma progressions, 6 sepsis, 3 attributed to cardiac failure and 1 to pulmonary embolism. The most frequent side-effects were hematological: febrile neutropenia (15 patients) and cardiac: acute failure (4 patients). ConclusionOur results in older patients with low grade lymphoma compare favorably with results in younger population. IPI and FLIPI only affect OS whereas geriatric evaluation with Charlson score is not relevant, possibly due to the small number of patients and short follow-up.These results prompt us to realize prospective studies in this population, reducing toxicity and improving efficacy with novel approach. [Display omitted] Disclosures:No relevant conflicts of interest to declare.

Cost-Effectiveness of White Blood Cell Growth Factor Use among a Large Nationwide Cohort of Elderly Non-Hodgkin's Lymphoma Patients Treated with Chemotherapy

Objective To determine the cost-effectiveness (as measured as cost per life-year saved) of white blood cell growth factor or colony-stimulating factor (CSF) use among a large cohort of elderly non-Hodgkin's lymphoma (NHL) patients in a real-world setting. Methods We identified 13,203 NHL patients from the Surveillance, Epidemiology, and End Results (SEER)-Medicare database who received the diagnosis from 1992 to 2002 and who received chemotherapy within 12 months of diagnosis. Benefit (effectiveness) of CSF use (primary and secondary prophylaxis) was measured as observed improvement in overall survival. Costs for each patient were calculated by adding the cumulative reimbursement amounts from Medicare claims. Cost-effectiveness was estimated by modeling the joint influence of CSF use on both costs and effectiveness using a propensity-score net monetary benefit approach. Results Primary prophylactic CSF use was cost-effective at lower willingness-to-pay thresholds, whereas at higher thresholds, not providing prophylactic CSF became the cost-effective strategy. For secondary prophylactic CSF use among patients experiencing neutropenia, fever, and/or infection, the opposite trend was observed. For low willingness-to-pay thresholds (<$20,000 per life-year gained), not administering CSF was the cost-effective strategy, whereas CSF use became cost-effective as willingness to pay increased (from $100,000+ per life-year gained). Conclusion To our knowledge, this is the first large population-based study to empirically measure the cost-effectiveness of CSF among NHL patients treated with chemotherapy. CSF use as primary or secondary prophylaxis may be a cost-effective strategy depending on society's (or payers') willingness to pay for improvements in outcomes.

Multicenter Analysis of 150 Very Elderly Non-Hodgkin's Lymphoma (NHL) Patients: Impact of Comorbidities and Response to Initial Therapy on Survival

AbstractAbstract 3124 Background:The incidence of NHL increases exponentially with rising age. The most rapidly growing segment of the population is persons > age 65 years, especially > age 80. As a percentage of US population, the age group >80 years has increased by >250% from 1960 to 2000. Furthermore, persons >80 years will more than double within 20 years. However, little data is available regarding the characteristics or outcomes of very elderly NHL patients (pts). Methods:We completed a multicenter retrospective analysis of very elderly NHL pts (=/> 80) diagnosed (dx) between 9/99-9/09 at 4 Chicago centers. Detailed pt and disease characteristics were collected including comorbidities, which were assessed using the Cumulative Illness Rating Scale for Geriatrics (CIRS-G). Pts were also classified if they were “fit” (i.e., preserved activities of daily living (ADLs), <3 grade 3 CIRS-G, no grade 4, and no geriatric syndrome: dementia, delirium, depression, incontinence, falls, neglect/abuse, or failure to thrive). Result:We identified 150 pts (F:M 1.14) with a median age of 84 years (80-96). 74 pts had aggressive NHL histology: DLBCL n=56 (systemic n=49, primary CNS n=5, gastric n=1, PEL n=1), T-cell n=11 (peripheral n=7, Sezary n=4) and MCL n=7. 76 pts had indolent NHL: follicular n=32, mycoses fungoides n=16, MZL n=17, CLL/SLL n=8 and lymphoplasmacytic n=4. Disease characteristics at dx included: B symptoms 20%, PS 2–3 18%, marrow involvement 35%, >1 extranodal 20%, elevated LDH 38%, anemia 41%, thrombocytopenia 16%, renal insufficiency 25%, and 36% had a history of coronary artery disease. Additionally, 28% had prior malignancy. Comorbidities were common; 77% of pts had a cumulative CIRS score >6, while 74% had a grade 3–4 CIRS-G in at least 1 category. Furthermore, 33% were classified as “not fit” at NHL dx, 12% had loss of ADLs, while 22% had a geriatric syndrome at time of NHL dx. 57% had stage III/IV disease. Pts with aggressive B cell histology received a rituximab (R)-containing regimen 85% of the time, while 84% of all aggressive NHL received at least one cycle with an anthracycline. Initial therapy for B cell indolent NHL were: observation (24%), R alone (35%), R-chemotherapy (CT) (31%), radiation (8%), and CT alone (2%). Among all pts, the overall response to first treatment was 68% (CR 49%). With 40-month median follow-up (1-120), 3-year EFS (event-free survival) and OS (overall survival) for all pts were 43.8% and 70.3%, respectively (stage I/II: EFS 49% and OS 81%; stage III/IV: EFS 42% and OS 65%; p=0.039 and p=0.09, respectively). Among aggressive NHL (n=74), 3-year EFS and OS were 55% and 64% (stage I/II: EFS 86% and OS 94%; stage III/IV: EFS 45% and OS 57%; p=0.0006 and p=0.03, respectively), while for indolent NHL (n=76), the 3-year EFS and OS were 34% and 77%, respectively (Figures 1–3). Prognostic factors predicting survival are shown in Table 1. In multivariate regression analyses, no response to initial therapy (i.e., SD/PD) predicted for significantly inferior EFS and OS (HR 5.45 [2.02-13.65], p=0.0007 and HR 6.88 [1.66-28.44], p=0.008, respectively). Conclusion:Long-term survival of very elderly NHL was feasible with 64% and 77% 3-year OS for aggressive and indolent histologies, respectively. However, comorbidities as well as a designation of “unfit” portended a significantly inferior outcome in univariate models. Primary resistance to initial therapy occurred in 32% of pts and also predicted for poor prognosis. Given the rising incidence and prevalence of very elderly NHL, prospective examination of this subset of pts is strongly warranted. [Display omitted] [Display omitted] [Display omitted] Disclosures:No relevant conflicts of interest to declare.

The Risk of Secondary Myelodysplastic Syndrome/Acute Leukemia Following High-Dose Yttrium-90 Ibritumomab Tiuxetan Is Analogous to That Observed Following High-Dose Chemotherapy: a Matched-Pair Analysis In Non-Hodgkin Lymphoma Patients.

AbstractAbstract 1289 Introduction:Myeloablative doses of Yttrium-90 (90Y)-Ibritumomab Tiuxetan combined with tandem autologous peripheral blood stem cell (PBSC) support can be safely administered to patients aged up to 76 years (Devizzi L et al, J Clin Oncol 2008). Whether marrow exposure to myeloablative doses of radiolabelled antibodies (hd-radio-immunotherapy) could increase the risk of secondary myelodysplastic syndrome and acute leukemia (sMDS/AL) remains a matter of concern. Therefore, we prospectively investigated by means of a longitudinal study the incidence of sMDS/AL in a cohort of high-risk non-Hodgkin lymphoma (NHL) patients receiving hd-radio-immunotherapy. The cumulative incidence of sMDS/AL in the study group was compared with that observed in a historical group of patients autografted following chemotherapy-based myeloablative conditioning. Additionally, to further investigate marrow damage induced by hd-radio-immunotherapy, hematopoietic and stromal progenitors, as well as telomere length (TL) were assessed. Patients and Methods:From July 2004 through December 2007, 53 relapsed/refractory (n= 36) or de novo high-risk (n= 17) NHL patients (median age, 64 years; range, 26 – 76 years) received a high-dose sequential (HDS) chemotherapy program, including a myeloablative phase with 90Y-Ibritumomab Tiuxetan (1.2 mCi/kg body weight). Patients were monitored for frequency of colony-forming cells (CFCs), cytogenetic and TL analysis. Bone marrow (BM) samples were collected prior to hd-radio-immunotherapy, every six months for two years and annually thereafter. The study was approved by the Institutional Ethical Committee and written informed consent was obtained from each patient. The study group included 29 patients with aggressive lymphoma (diffuse large B-cell lymphoma, n = 19; mantle cell lymphoma, n = 8; Richter syndrome, n = 2) and 24 with indolent NHL subtypes (follicular lymphoma, n = 20; marginal zone lymphoma, n = 3; lymphocytic lymphoma, n = 1). Thirty patients were relapsed after one (n=15) or more (n=15) previous chemotherapy regimens, 6 patients were refractory and 17 patients were previously untreated with high-risk prognostic index. Pre-exposure to alkylating agent involved 68% of the patients. A historical group of 55 NHL patients who received an analogous HDS program with final chemotherapy-based autografting was used as control group. Study and control groups were pair-matched for age, gender, histological subtype, disease status at transplant and type of grafted PBSC. Results:At a median follow-up of 49 months (range, 32 – 74), 4 out of 53 patients of the study group developed sMDS/AL at 6, 12, 27 and 36 months from transplant. According to WHO criteria, refractory anemia with excess of blasts 1 (RAEB-1) was diagnosed in one patient, whereas refractory cytopenia with unilineage dysplasia (RCUD) was diagnosed in the other three cases, with acute leukemia transformation being observed in two patients at 12 and 18 months after initial detection of abnormal cytogenetics, respectively. The cumulative incidence of sMDS/AL resulted of 8.29% at 5-years. An analogous 5-year cumulative incidence of 8.05% was observed in the historical control group autografted following a chemotherapy-based conditioning. Radioimmunotherapy-treated patients showed a significant but transient decrease in granulocyte-macrophage colony forming unit (CFU-GM) at 6 months after transplant, with recovery to baseline values at 12 months. Multilineage colony-forming units (CFU-Mix), erythroid burst-forming units (BFU-E) and fibroblast CFU (CFU-F) were not show significantly affected over time. In contrast, a progressive and significant decrease in BM TL was evident from 12 months after transplant. Conclusion:In our series of elderly NHL patients receiving hd-radio-immunotherapy, the incidence of sMDS/AL was found increased compared to recently reported series of younger lymphoma patients receiving chemotherapy-based conditioning. However, the increased risk of sMDS/AL was not associated with the type of myeloablative conditioning, i.e. chemotherapy vs radio-immunotherapy. Other factors may have favored the development of sMDS/AL, including advanced age at transplant, extensive pre-transplant therapy and type of reinfused PBSC. The observed progressive TL loss gives support to the concept that TL loss might be involved in sMDS/AL development. Disclosures:No relevant conflicts of interest to declare.

Use of white blood cell growth factors and risk of acute myeloid leukemia or myelodysplastic syndrome among elderly patients with non‐Hodgkin lymphoma

The current study was conducted to evaluate the association between colony-stimulating factor (CSF) use and the risk of developing therapy-related myelodysplastic syndromes or acute myeloid leukemia (t-MDS/AML) among a large cohort of elderly patients with non-Hodgkin lymphoma (NHL) who were treated with chemotherapy. A total of 13,203 NHL patients were identified from the Surveillance, Epidemiology, and End Results-Medicare database who were diagnosed from 1992 through 2002. Patients were followed from their initial chemotherapy date until the date they were diagnosed with t-MDS/AML, death, or last follow-up (October 31, 2006), whichever occurred first. Overall, 40% (n = 5266) of patients received CSF. During the follow-up period (median follow-up, 2.9 years [range, 1-14.7 years]), 272 (5.2%) patients who were treated with CSF developed t-MDS/AML, compared with 230 (2.9%) patients who did not (P < .0001, log-rank test). The 5-year incidence of t-MDS/AML for patients receiving CSF was 14.1 per 1000 person-years compared with 8.3 per 1000 person-years for patients not receiving CSF. In a multivariable Cox regression analysis adjusted for gender, histology, stage, comorbidities, radiotherapy, and chemotherapy agent, CSF use was found to be independently associated with a 53% increased risk of t-MDS/AML (hazard ratio [HR], 1.53; 95% confidence interval [95% CI], 1.26-1.84). The observed association between CSF use and t-MDS/AML persisted across histologic subgroups (ie, diffuse large B-cell lymphoma, follicular lymphoma, and others). Patients who received both CSF and antimetabolite chemotherapy were found to have a 2.5-fold increased risk of t-MDS/AML (HR, 2.49; 95% CI, 1.91-3.26) compared with patients who received neither agent. The current study, which to our knowledge is the first large population-based study published to date, demonstrated that the administration of CSF among elderly NHL patients receiving chemotherapy was associated with an increased risk of t-MDS/AML, although the absolute risk was low.

Abstract B129: Use of white blood cell growth factors and risk of acute myeloid leukemia or myelodysplastic syndrome among elderly non-Hodgkin's lymphoma patients

Abstract Therapy-related myelodysplastic syndromes and acute myeloid leukemia (t-MDS/AML), defined as MDS or AML occurring after myelosuppressive chemotherapy and/or radiation therapy, are devastating long-term complications of cancer therapy. White blood cell growth factors (CSFs) are supportive care agents intended to minimize risk of febrile neutropenia in patients receiving chemotherapy. However, evidence suggests that CSFs may increase risk of t-MDS/AML, possibly due to the observation that CSFs not only stimulate the proliferation and differentiation of hematopoietic stem cells, but also interfere with apoptosis. The purpose of this study was to evaluate the association between CSF use and t-MDS/AML among a large population-based cohort of elderly non-Hodgkin's lymphoma (NHL) patients treated with chemotherapy. We identified 13,203 NHL patients from the Surveillance, Epidemiology, and End Results (SEER)-Medicare database diagnosed from 1992 to 2002 who received chemotherapy within 12 months of diagnosis. Patients were followed from their initial chemotherapy date until t-MDS/AML development, death, or end of study period (October 31, 2006). Overall, 40% (n=5,266) of patients received CSF. A total of 272 (5.2%) of patients receiving CSF developed t-MDS/AML vs. 230 (2.9%) who did not receive CSF: there was a statistically significant higher incidence of t-MDS/AML among patients receiving CSF compared to patients not receiving CSF (log-rank p&amp;lt;0.0001). In a multivariable Cox regression analysis adjusting for gender, histology, stage, comorbidities, chemotherapy dates, and chemotherapy agent, CSF use was independently associated with a 53% increased risk of t-MDS/AML (HR 1.53; 95% CI 1.26 – 1.84). A dose-response relationship was observed, with t-MDS/AML risk increasing by quartile of CSF claims. In an evaluation of plausible biologic interactions, we found that patients who received both CSF and antimetabolite chemotherapy had a 2.5 fold increased risk of t-MDS/AML (HR 2.49; 95% CI 1.91 – 3.26) vs. patients who received neither agent (p-interaction=0.04). This observation has added clinical significance considering that approximately 10% of the overall population received this therapeutic combination. To our knowledge, this is the first large population-based study to evaluate the association between CSF use and t-MDS/AML risk among NHL patients. Findings support our hypothesis that the administration of CSF among elderly NHL patients receiving chemotherapy may increase the risk of t-MDS/AML, even though the absolute risk is low in these populations. Future studies are necessary to verify these results and to determine the potential clinical implications of the observed interaction between CSF use and antimetabolite chemotherapy. Citation Information: Cancer Prev Res 2010;3(1 Suppl):B129.

Factors Associated With Immunotherapy Use Among Newly Diagnosed Cancer Patients

Immunotherapy represents a newer modality for cancer treatment with substantial health benefits. However, the high costs of immunotherapy may create access barriers. To examine factors associated with the utilization of immunotherapy among newly diagnosed cancer patients. Analysis of a large national cancer registry data, the National Cancer Data Base, that represents approximately 75% of newly diagnosed cancer patients in the US. Patient diagnosed with non-Hodgkin lymphoma (NHL), metastatic breast cancer (MBC), or metastatic colorectal cancer (MCRC). Factors associated with utilization of immunotherapy in NHL, MBC, or MCRC. The study included 207,581 and 42,804 patients diagnosed with NHL and MBC between 1998 and 2004, respectively (based on approval of rituximab in 1997 and trastuzumab in 1998); and 16,027 patients diagnosed with MCRC in 2004 (based on approval of cetuximab and bevacizumab in 2004). Immunotherapy use varied significantly by age, race, insurance status, year of diagnosis, and type of treatment facilities, with largest effects observed in years of diagnosis, followed by insurance status. Among young cancer patients, we found that compared with uninsured patients, the odds of receiving immunotherapy were 1.61, and 2.13 for privately insured MBC, and MCRC patients, respectively, and were in the range of 1.13 to 19.23 for privately insured NHL patients. For elderly NHL patients, those with secondary insurance in addition to Medicare were 1.26 to 8.24 times more likely to receive immunotherapy than those with Medicare alone. The disparities observed in this study suggest that additional efforts are required to ensure that all cancer patients receive timely and appropriate treatment.