Non-Hodgkin's Lymphoma In Elderly Research Articles

Evaluation of the cachexia index using a bioelectrical impedance analysis in elderly patients with non-Hodgkin's lymphoma: A single-center prospective study.

Cancer cachexia is a disorder that affects patient outcomes. The present study prospectively evaluated the prognostic value of the cachexia index (CXI) in elderly patients with non-Hodgkin's lymphoma (NHL). We prospectively analyzed 51 elderly patients who were diagnosed with NHL at our institution. CXI was calculated as follows: CXI = SMI × Alb/NLR (SMI: skeletal muscle index, Alb: serum albumin, NLR: neutrophil-to-lymphocyte ratio). SMI was measured by a bioelectrical impedance analysis (BIA) using the InBody 720. We determined the sex-specific cutoff values of the CXI by a receiver operating characteristic curve analysis and divided all patients into low- and high-CXI groups. The median age at the diagnosis was 78years (60-93years), and 28 (55%) were male. The histologic subtypes were B-cell lymphoma in 49 patients and T-cell lymphoma in 2. Twenty-eight (55%) patients were categorized into the high-CXI group, and 23 (45%) were categorized into the low-CXI group. The overall survival (OS) in the low-CXI group was significantly shorter than that in the high-CXI group (3-year OS, 70.4% vs. 95.7%, p = 0.007). Among 23 patients with DLBCL, patients with low-CXI had shorter OS than those with high-CXI (3-year OS, 55.6% vs. 92.9%, p = 0.008). On the other hand, sarcopenia had less impact on the clinical outcome of DLBCL patients. Low-CXI was associated with poor outcomes in elderly NHL and the CXI may be a clinical useful index for predicting prognosis. Further large prospective studies are needed to verify this conclusion.

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

Elderly Aggressive-Histology Non-Hodgkin's Lymphoma: First-Line VNCOP-B Regimen Experience on 350 Patients

Age is a risk factor and a prognostic parameter in elderly aggressive-histology non-Hodgkin's lymphoma (NHL) patients. Several adapted chemotherapeutic regimens have recently been designed and tested on elderly patients. Several of these trials have shown that older aggressive-histology NHL patients can benefit from specific and adequate treatment capable of curing a percentage of these patients. Between January 1992 and September 1997, 350 previously untreated aggressive-histology NHL patients greater than 60 years of age were treated with a combination therapy including cyclophosphamide, mitoxantrone, vincristine, etoposide, bleomycin, and prednisone (VNCOP-B). Complete remission (CR) was achieved by 202 (58%) patients and partial remission (PR) by 87 (25%), whereas the remaining 61 (17%) patients were nonresponders. The overall response rate (CR + PR) was 83%. Clinical and hematologic toxicities were modest, because 71% of the patients received granulocyte colony-stimulating factor (G-CSF). The CR rates for the three age groups (60 to 69, 70 to 79, and >/=80 years) were similar: 61%, 59%, and 56%, respectively. At 5 years, the relapse-free survival rate was 65%, the overall survival rate was 49%, and the failure-free survival rate was 33%. In the multivariate analysis, prognostic factors associated with longer survival or longer relapse-free survival turned out to be localized disease stage (P =.001) and good performance status (P =.0002). Application of the International Prognostic Factor Index was significantly associated with outcome (P =.001). These data confirm on a large cohort of patients that the VNCOP-B regimen is effective in inducing good CR and relapse-free survival rates with only moderate toxic effects in elderly aggressive-histology NHL.

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.

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.

166 - Assessing Individual Comorbidities in Elderly Non-Hodgkin Lymphoma (NHL) Patients Undergoing Autologous Stem Cell Transplant (ASCT)

166 - Assessing Individual Comorbidities in Elderly Non-Hodgkin Lymphoma (NHL) Patients Undergoing Autologous Stem Cell Transplant (ASCT)

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.

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.

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.

Analysis for clinicopathological features, therapy and prognosis of 30 elderly patients with non-Hodgkin's lymphoma

The purpose of this study was to explore the clinicopathological features, therapy and prognostic factors of elderly patients with non-Hodgkin's lymphoma (NHL). The clinical data including general clinical characteristics, pathological features, chemotherapy selection and treatment response of 30 patients with NHL in our hospital from January 2003 to December 2012 were analyzed retrospectively. The survival was analyzed by using Kaplan-Meier methods, and the prognosis was evaluated by COX regression multivariate analysis model. The clinical parameters selected include age, Ann Arbor stage, international prognostic index (IPI), B symptom and lactate dehydrogenase (LDH) levels. The results showed that all the patients suffered from underlying disease, and the cardiovascular disease (hypertension, coronary heart disease, arrhythmia) is the most common, and minority (8/30) combined with secondary tumor, the 63% (19/30) cases had B symptoms at diagnosis. only 2 cases were diagnosed as T-cell lymphoma; the 93% (28/30) cases combined with B-cell lymphoma, 57% (17/28) of them combined with diffuse large B-cell lymphoma. Ann-Arbor stage ≤ IIwas 37% (11/30);10(37%) patient's IPI score was ≤ 2, and 67% (20/30) was scored 3-5; 13(43%) patient's serum LDH level was abnormal. Modified R-CHOP chemotherapy was given individually on the basis of clinical features. The patients achieved complete remission, partial remission, stable disease, or progressive disease accounted for 14 (46.7%), 13 (43.3%), 1 (3.3%), and 2 (6.7%), respectively; the total reaction rate was 90% after 4 cycles of chemotherapy; the overall survival (OS) rate at 1 and 2 years was 73.3% and 43.3%, and progression-free survival (PFS)rate at 0.5 and 1 years was 62.2% and 54.9%; multivariate analysis by COX regression showed that B symptoms and Ann-Arbor stage were independent factors (P = 0.014, 0.039; RR = 6.678, 4.939, respectively) affecting the OS of elderly NHL, and IPI score affected PFS independently. It is concluded that elderly patients with NHL usually are of late stage at newly diagnosis and have suffered from underlaying diseases. Besides strengthening supportive treatment, modified R-CHOP chemotherapy should be given individually according to different prognosis. B symptoms and Ann-Arbor stage >II are indicators for poor prognosis of elderly NHL.

Disparity In Clinical Outcomes Of Elderly Patients With Non-Hodgkin Lymphoma After Autologous Hematopoietic Stem Cell Transplantation According To Area Of Residence

BackgroundOur previous studies have shown little or no difference in the overall survival (OS) of urban over rural cohorts with lymphoma. Autologous hematopoietic stem cell transplantation (Auto-HSCT) is a frequently used treatment for non-Hodgkin lymphoma (NHL), but the elderly tend to tolerate transplant less well than their young counterparts. Increased prevalence of chronic conditions, comorbidity and frailty, serve to further complicate treatment in the elderly. We hypothesize that the same factors that contribute to the complexity of Auto-HSCT in the elderly may also contribute to outcome disparity according to area of residence. AimTo determine if area of residence is an independent risk factor for the following clinical outcomes: relapse, non-relapse mortality (NRM), disease-free survival (DFS) and OS following Auto-HSCT in the elderly with NHL. MethodsThis is a retrospective cohort study of patients (pts) age ≥60y who underwent first Auto-HSCT for NHL between 1985 and 2012. Using pts' residential ZIP codes at the time of transplant, the primary area of residence was categorized as urban or rural according to the Rural-Urban Commuting Area Codes classification system. Multivariate analyses (MVA) were performed using Cox proportional hazards regression analysis to evaluate the association between area of residence and all outcomes while adjusting for significant patient-, disease-, and treatment-related variables. ResultsDuring the study period, 1616 pts underwent Auto-HSCT for NHL; 321 (20%) of whom were elderly. A total of 286 (89%) had classifiable U.S. ZIP codes: urban (n=182, 64%) and rural (n=104, 36%). The median age was 65y (range 60-77), 64% males, and 93% of the NHL types are high-grade. We failed to detect significant differences in all patient-, disease-, and treatment-related factors between the two cohorts except for disease stage at the time of transplant (p=0.03); urban pts tend to be in relapse at the time of transplant (35% vs 25%), while rural pts tend to be in second or more complete remission ( 34% vs 18%). MVA results are summarized in the table below. We failed to detect differences in the risk of relapse and NRM between urban and rural cohorts. Both risk for treatment-failure (inverse of DFS) and mortality were time-dependent such that the association between area of residence and outcome varied before and after 6 months post-transplant. The risk of treatment-failure and mortality was significantly lower in the rural cohort compared to the urban cohort after 6 months; while similar in the first 6 months. Age and year of transplant were significantly associated with DFS and OS; disease stage at the time of transplant was not significant. The probability of OS (see figure) at 5 and 10 years post-transplant in urban and rural cohorts were 44% vs 54% and 26% vs 38%, respectively. The causes of death were not statistically different between the two groups with most dying from relapse, multi-organ failure and second malignancies. [Display omitted] [Display omitted] ConclusionsThe absence of clear differences in characteristics of elderly NHL pts who underwent Auto-HSCT according to area of residence suggests a similar selection process. The better DFS and OS after 6 months that persist over time and is not explainable by marked differences in relapse, NRM or treatment received suggests interplay of other non-biological factors including: attitudes, health seeking behaviors, environment-related factors, or health care follow-up. Further research is needed to determine the underlying cause of the observed outcome disparity among elderly NHL transplant pts. Disclosures:Armitage:Ziopharm: Consultancy; Roche: Consultancy; Genetech : Consultancy; Seattle Genetics: Consultancy; GlaxoSmith Kline : Consultancy; Tesaro bio, Inc. : Membership on an entity's Board of Directors or advisory committees. Vose:Sanofi-Aventis US, Inc.: Research Funding; Pharmacyclics: Research Funding; Onyx Pharmaceuticals: Research Funding; Millennium: Research Funding; Janssen Biotech : Research Funding; Incyte Corp.: Research Funding; GlaxoSmithKLINE: Research Funding; Genentech: Research Funding; Celgene: Research Funding; Bristol-Myers Squibb: Research Funding; Allos Therapeutics/Spectrum: Research Funding; US Biotest, Inc. : Research Funding.

Multicenter Analysis of Very Elderly Indolent and Aggressive Non-Hodgkin Lymphoma (NHL): Impact of Functional Status on Outcome,

Abstract 3668 Background:The prevalence of NHL in patients (pts) ≥ 80 years has recently tripled; however, data on prognostic factors and treatment for this very elderly population is sparse. Methods:A multicenter retrospective analysis of NHL pts ≥80 years diagnosed between (1999–2009) was completed. Detailed characteristics obtained include geriatric syndromes (GS), activities of daily living (ADLs), and co-morbidities using the Cumulative Illness Rating Scale-Geriatrics (CIRS-G). Further, univariate associations with survival were determined, while a multivariate Cox regression proportional hazards model was performed. Results:We identified 303 pts: 170 aggressive NHL (84% B-cell and 16% T-cell) and 133 indolent NHL (82% B-cell and 18% T-cell). Median age was 84 years (range 80–95). Poor performance status (PS), high LDH, and extranodal disease were more common in aggressive vs. indolent NHLs (P=0.004, 0.005, and 0.002, respectively). Furthermore, aggressive NHL pts presented more frequently with advanced stage and higher relative prognostic scores (P=0.0002 and 0.003 respectively). Loss of any ADL was more frequent in aggressive histology (P=0.002). Diffuse large B-cell NHL was the most common histology overall, while follicular lymphoma was the most diagnosed indolent NHL. At least one GS was present in 80 pts (26%) with dementia being most common (26%). Loss of at least one ADL was seen in 14%, while 30% of pts were considered “non-fit” at diagnosis. Of available treatment data in aggressive B-NHL, 62% received rituximab (R)-containing regimen and 18% received chemotherapy without R. Those with aggressive T-cell NHL were treated with systemic therapy in 74%, topical in 15%, radiation in 4%, and no therapy in 7%. Indolent B-cell NHL had observation in 38% for a median of 26 months, R alone in 21%, R plus chemotherapy in 15%, radiation alone in 7%, and chemotherapy alone in 9%. Cutaneous T-cell pts received topical therapies in 42%, systemic therapy in 29%, and radiation alone in 17%. At 49-month median follow-up, 4-year progression-free (PFS) and overall survival (OS) for aggressive NHL were 31% and 44%, respectively (stage I/II: PFS 53% and OS 66%; stage III/IV: PFS 20% and OS 32%; p<0.0001 and 0.0002, respectively). Four-year PFS and OS for indolent NHL were 44% and 66%, respectively, regardless of stage. Prognostic factors predicting OS and PFS on univariate are detailed in Table 1. Cox multivariate regression analysis identified two factors predicting inferior outcome for both NHL groups: lack of complete response (CR) (indolent: PFS, P=0.03; OS, P=0.01; aggressive: PFS, P<0.0001; OS, P<0.0002) and loss of ADLs (indolent: PFS, P=0.003; OS, P=0.0004; aggressive: PFS, P=0.002; OS, P<0.0001).Table 1Prognostic factors associated with survival (univariate analysis)Aggressive NHLPFSOSHR95% CIPHR*95% CIPECOG PS 2-41.69(1.12, 2.56)0.012.35(1.48, 3.73)0.0003Any CIRS score 41.42(0.91, 2.22)0.121.99(1.24, 3.19)0.004Loss of any ADL2.89(1.86, 4.50)<0.00013.57(2.53, 5.66)<0.0001Any geriatric syndrome1.31(0.88, 1.96)0.181.77(1.17, 2.69)0.007Elevated creatinine1.51(0.99, 2.30)0.0531.67(1.08, 2.58)0.02Elevated LDH1.55(1.05, 2.27)0.031.68(1.10, 2.57)0.02Hypoalbuminemia1.15(0.99, 1.34)0.071.35(1.15, 1.58)0.0003Stage III/IV2.40(1.54, 3.74)0.00012.49(1.52, 4.08)0.0003Marrow involvement1.93(1.22, 3.06)0.0051.60(0.98, 2.61)0.06↑ IPI or FLIPI1.91(1.26, 2.90)0.0022.26(1.43, 3.57)0.0005Response: no CR2.88(1.91, 4.32)<0.00012.35(1.51, 3.67)0.0002Indolent NHLPFSOSHR*95% CIPHR*95% CIPLoss of any ADL3.58(1.61, 7.96)0.0025.56(2.27, 13.61)0.0002Any geriatric syndrome1.86(1.13, 3.05)0.011.69(0.97, 2.94)0.06B symptoms1.34(0.64, 2.81)0.452.11(0.98, 4.54)0.055Weight loss >10%1.28(0.67, 2.48)0.452.81(1.43, 5.52)0.003ECOG PS 2-41.14(0.84, 1.54)0.401.36(1.01, 1.83)0.045Response: no CR2.19(1.18, 4.05)0.012.91(1.37, 6.20)0.006 Conclusion:To our knowledge, this represents the largest analysis of very elderly NHL reported to date. We identified that loss of ADL's and lack of CR to initial treatment were robust predictors of survival in very elderly NHL, irrespective of histology, and they superseded the prognostic value of either PS or age. Geriatric assessments, including ADLs, are powerful predictors of outcome in very elderly NHL and should be prospectively studied. Disclosures:No relevant conflicts of interest to declare.

Multicenter analysis of more than 300 very elderly non-Hodgkin lymphoma (NHL) patients (pts): Impact of comorbidities and functional status on outcome.

8042 Background: Ages > 80 represent the most rapidly growing segment of society. Incidence of NHL rises exponentially with age; however, sparse data exist among the > 80 pt group. Methods: We completed a multicenter retrospective study with initial NHL diagnosis = > age 80 (1999 – 2009). Comorbidities were scored with the Cumulative Illness Rating Scale/Geriatrics (CIRS-G). Geriatric syndromes and activity of daily livings (ADLs) were recorded. Results: 303 pts: 170 aggressive (Agg) (143 B-cell) and 133 indolent (Ind) (109 B-cell). Median age was 83 (80-95), 52% stage III/IV, and PS 2-4 in 27%. A geriatric syndrome was present in 26%, 30% were non-fit, 18% had 1 CIRS-G grade 4, while 14% had loss of ADLs. 66% of Agg B-cell received rituximab (R) based therapy (Tx). For Ind NHL, 39% were observed for median of 26 months; when Tx, R-based programs was used in 44%. Overall response (OR) was 65% (44% CR) in Agg and 60% (32% CR) in Tx Ind pts. At 49-month median F/U (6-149), 4-year PFS and OS for Agg were 31% and 44%, respectively (stage I/II: PFS 53%/OS 66%; stage III/IV: PFS 20%/OS 32%; p=<.0001 and .0002, respectively). 4-year PFS and OS for Ind were 44% and 66%, respectively, with no differences between stages. See below table for univariate prognostic factors. Multivariate cox regression for Agg NHL showed that stage III/IV, ADL loss, and < CR correlated with inferior PFS/OS. The latter 2 were significant for Ind NHL. Conclusions: Geriatric assessment tools are powerful predictors of outcome complementing standard prognostic features. Incorporation of geriatric prognostic models should be prospectively studied. Factors PFS (p/HR) OS (p/HR) Agg NHL (n=162). PS 2-4 .01/1.69 .0003/2.35 ↑LDH .03/1.5 .02/1.68 ↓ Albumin NS .0003/1.35 ↓ ADLs <.0001/2.89 <.0001/3.87 ↑ Creatinine NS .02/1.67 ↓ Platelets NS .02/1.73 Stage III/IV .0001/2.4 .0003/2.49 BM + .005/1.93 NS No CR to 1st Tx <.0001/2.88 .0002/2.35 Any CIRS 4 NS .004/1.99 Any geriatric syndrome NS .007/1.77 IPI 3-5 .002/1.91 .005/2.26 Ind NHL (n=126). Weight loss > 10% NS .003/2.81 PS 2-4 NS .045/1.39 No CR to 1st Tx .01/2.19 .006/2.91 ↓ ADLs .002/3.58 .0002/5.56 Any geriatric syndrome .01/1.86 NS Abbreviations: NS, not significant; BM, bone marrow; HR, hazard ratio.

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.