Late Morbidity and Mortality Among 2-Year Survivors of Non-Hodgkin Lymphoma (NHL) Diagnosed in the Elderly - a Population-Based Study

Abstract Background Over 55% of all NHL is diagnosed after age 65y. Declining death rates have resulted in a growing population of older NHL survivors. However the long-term morbidity and mortality in this population remains unknown. This study addresses this gap by evaluating post-cancer late morbidity and mortality experienced by 2y NHL survivors diagnosed at age ≥65, using data from SEER linked with Medicare claims, and an age, sex and race frequency-matched comparison group derived from and representing 5% of the Medicare non-cancer population. Methods Individuals ≥67y of age (to allow for identifying pre-cancer conditions) with incident NHL diagnosed between 1/1/2000 and 12/31/2008 and surviving at least 2y (n=10,958) were included in this analysis. Survivors were diagnosed as aggressive NHL (diffuse large B cell, Mantle cell, Burkitt's: n=7,004) or indolent NHL (follicular, marginal zone, chronic lymphocytic and small cell lymphocytic leukemia: n=3,954). New-onset morbidity: Competing risk cumulative incidence functions were used to assess the development of new-onset morbidity (congestive heart failure [CHF], cardiovascular disease [CVD: stroke/ myocardial infarction], and subsequent malignant neoplasms [SMNs]). Cox regression models evaluated predictors associated with new-onset morbidity. Predictors included lymphoma type (aggressive vs. indolent), age at NHL diagnosis, stage, sex, SES, race/ethnicity, radiation site, chemotherapy (none, rituximab only, anthracycline based chemotherapy (ABC), non-ABC chemotherapy), and pre-cancer comorbidity (Charlson Comorbidity Index + hypertension + depression). Late mortality: Kaplan-Meier methods were used to evaluate all-cause late mortality and cumulative incidence to evaluate cause-specific mortality. Results: The median age at NHL diagnosis was 76y (range: 67-103) with a median survival of 7y (2-14y); 55% were male, 90% were Non-Hispanic White and 39% resided in an area where >10% of the population lived below poverty level; 64% were diagnosed with aggressive NHL; 39% received ABC therapy and 20% received radiation (n=2,219). New-onset morbidity: The 10y cumulative incidence of new-onset morbidity was greater among survivors compared to the comparison group: CVD (57.4% vs. 53.8%, p=<0.001), CHF (56.0% vs. 43.1%, p<0.001). Controlling for pre-cancer comorbidities, cancer survivors were at 1.7-fold increased risk of developing new-onset CHF (p<0.001), 1.16-fold increased risk for CVD (p<0.001) compared to non-cancer population. Multivariable analysis among survivors revealed that those who received ABC were at 1.21-fold increased risk of developing CHF (p<0.001) and those treated with non-ABC were at a 1.13-fold increased risk (p=0.01). Survivors who received radiation to the chest/axilla were 1.14-fold more likely to have a CVD compared to those without radiation (p=0.03). The 10y cumulative incidence of SMNs among NHL survivors was 21.6%. The most common SMNs were lung cancer (13.1% of all SMNs) and prostate cancer (11.2%). Survivors who received any radiation were at 1.37-fold (p<0.001) increased hazard of developing an SMN compared to those without radiation. Importantly, the 10y cumulative incidence of one or more of the new-onset morbidities (CHF, CHD or SMNs) was 77.3% among the NHL (Fig 1). Late mortality: Conditional on surviving the first 2y, the overall survival was 61.2% at 5y from diagnosis and 35.8% at 10y, significantly lower than matched controls at equivalent time points (78.7%, 57.5%; p<0.0001) (Fig 2). Controlling for pre-cancer comorbidities, individuals with aggressive NHL were at 2.0-fold (p<0.001) increased risk and those with indolent NHL were at 1.9-fold (p<0.001) increased risk of late death compared with the matched control population. Among survivors, the 10y cumulative incidence of lymphoma-related death was 38.1%, CVD-related death (19.9%) and SMN-related deaths (13.6%). Conclusion The incidence of new-onset morbidity exceeds 75% at 10yfrom diagnosis ofNHL in the elderly. Further, 2y NHL survivors are at a 2-fold increased risk for late mortality when compared with a non-cancer population. These findings provide evidence for the need for close long-term risk-based medical follow-up of elderly with NHL. Figure 1 Figure 1. Disclosures Mehta: Pharmacyclics: Research Funding; Medimmune: Research Funding; Bristol Myers Squibb: Research Funding; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees; Roche Genentech: Research Funding; Incyte: Research Funding; Merck: Research Funding.

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New-onset congestive heart failure (CHF) and cardiovascular disease (CVD) in older colorectal cancer (CRC) survivors: A population-based study.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.10011 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 10011-10011

Author(s):

Kelly Kenzik ◽

Courtney Balentine ◽

Smita Bhatia ◽

Grant Richard Williams

Keyword(s):

Cumulative Incidence ◽

Cox Regression ◽

The Elderly ◽

Population Based ◽

Diabetic Patients ◽

Cumulative Incidence Functions ◽

Increased Risk ◽

History Of ◽

Incidence Functions ◽

New Onset

10011 Background: CRC is primarily a disease of the elderly. The high burden of pre-existing comorbidities alone or in concert with cancer treatment place the older patients with CRC at increased risk of new-onset morbidities, specifically, CVD and CHF. However, the magnitude of risk of new-onset morbidity, and its association with pre-existing comorbidities or treatment remain unknown. Methods: Using SEER-Medicare data, we evaluated individuals diagnosed with incident stage I-III CRC at age ≥66y between 1/1/2000 and 12/31/2011 who had survived ≥2y after diagnosis (n = 57,256; 77% with colon cancer). We compared these to an age, sex-, and race-frequency matched comparison group of non-cancer Medicare patients (n = 104,731). We evaluated new-onset CHF and CVD using competing risk cumulative incidence functions and multivariable Cox regression models. Results: The median age at diagnosis was 77y (66-106y); 45% males; and 85% non-Hispanic white. Median follow-up was 8y (2-14y) from diagnosis of CRC. Treatment included surgery for 99%, chemotherapy for 31%, and radiation for 12%. New-onset morbidity: The 10y cumulative incidence of new-onset CHF and CVD were 43.6% and 58.9%, respectively. After controlling for pre-cancer comorbidities, CRC survivors were at increased risk of new-onset CHF (HR 1.29) and CVD (HR 1.74) (all p < 0.001) compared to controls. Patients receiving radiation (HR 1.29) or 5-FU+oxaliplatin (HR 1.09) were at increased risk of CVD compared to those without those therapies (p < 0.001). Pre-existing diabetes (HR 1.16) and CHF (HR 1.21) independently increased the risk of CVD (p < 0.001). While 5FU+oxaliplatin did not increase the risk of CHF independently (HR 0.97), diabetic patients treated with 5-FU+oxaliplatin were at 1.71-fold increased risk of developing CHF (p < 0.001) when compared with those without pre-existing diabetes. Conclusions: Older CRC survivors are at increased of developing CHF and CVD. Monitoring survivors with a history of exposure to 5FU+oxaliplatin or radiation, and improving management of pre-existing comorbidities may reduce the burden of long-term morbidity for older CRC survivors.

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Autoimmune Hemolytic Anemia: A Disease of the Elderly and the Very Elderly with Increased Mortality and Increased Rates of Hospitalization for Thrombosis and Infection

Blood ◽

10.1182/blood-2020-137545 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 41-41

Author(s):

Julien Maquet ◽

Margaux Lafaurie ◽

Agnès Sommet ◽

Maryse Lapeyre-Mestre ◽

Guillaume Moulis

Keyword(s):

General Population ◽

Cumulative Incidence ◽

Research Funding ◽

The Elderly ◽

Evans Syndrome ◽

Very Elderly ◽

Risk Of Death ◽

Incidence Of Hospitalization

Introduction Autoimmune hemolytic anemia (AIHA) is a rare disease characterized by the destruction of red blood cells by warm or cold autoantibodies. Epidemiological data are lacking about AIHA incidence, the prevalence of associated disorders and the risk of death, thrombosis and infection as compared with the general population. This study was designed to answer these questions. Methods Patients were selected from the AHEAD cohort. This cohort is built in the French national health database (named Système national des données de santé, SNDS) linking sociodemographics, out-hospital and hospital data for the entire French population (67 million inhabitants). The AHEAD cohort is the cohort of all incident AIHA in France. Patients were selected between 2012-2017. The date of AIHA diagnosis was defined by the first hospital discharge diagnosis or the first long-term disease (recorded by general practitioners) of AIHA occurring after a prior observation period in the SNDS of at least two years. Patients were identified using the D59.1 code of the international classification of diseases, version 10 (positive predictive value: 90.0%). The incidence of AIHA was calculated in the whole French population, by age, sex and calendar months. Causes of secondary AIHA and Evans syndrome were searched in the year before the diagnosis of AIHA using long-term disease and hospital discharge diagnoses. Each patient was matched to five controls on age and sex from the general population. The follow-up ended on December 31, 2018. One- and five-year cumulative incidences of death, hospitalization for thrombosis and for infection were assessed in AIHA patients and in controls, with their 95% confidence intervals (95% CIs). Results During the study period, 9,663 incident AIHA patients were included. The median age was 69 years and 55.6 of the patients were female. The overall incidence of AIHA was 2.4 per 100,000 person-years (95% CI: 2.4 - 2.5). The incidence of AIHA in women during genital activity (15 - 45 years-old, 1.2 per 100,000 person-years, 95% CI: 1.1 - 1.3) was higher than in males of same age (0.7 per 100,000 person-years, 95% CI: 0.6 - 0.7). The incidence of AIHA was dramatically increased in the elderly (>75 years of age: 10.5 per 100,000 person-years; 95% CI: 10.2 - 10.8) and the very elderly (>90 years of age, 12.1 per 100,000 person-years; 95% CI: 11.1 - 13.2), as compared with people <50 year-old (0.9 per 100,000 person-years; 95% CI: 0.9 - 1.0). Incidences were higher in males than in females in people >65 year-old. This pattern was observed for both primary and secondary AIHA. There were no relevant variations of incidence by calendar months for both primary and secondary AIHA. AIHA was primary in 55.2% of cases, associated with hematological malignancy in 30.2% and with lupus in 5.2%. Evans syndrome accounted for 5.8% of AIHAs. The patients were matched with 47,753 controls. The overall follow-up in the cohort was 28,630 person-years. The 1-year cumulative incidence of death was 18.6% (95% CI: 17.8 - 19.4) in AIHA (in primary AIHA: 16.5%, 95% CI: 15.5 - 17.4), versus 3.1% (95% CI: 3.0 - 3.3) in controls. The 5-year cumulative incidence of death was 36.1% (95% CI: 34.9 - 37.2) in AIHA (in primary AIHA: 32.4%, 95% CI: 30.9 - 33.8) and 15.1% (95% CI: 14.7 - 15.5) in controls. The 1-year cumulative incidence of hospitalization for thrombosis was 6.0% (95% CI: 5.6 - 6.5) in AIHA (in primary AIHA: 5.7%, 95% CI: 5.1 - 6.4) versus 1.8% (95% CI: 1.7 - 1.9) in controls. The 5-year cumulative incidence of hospitalizations for thrombosis was 11.1% (95% CI: 10.4 - 11.8) in AIHA (in primary AIHA: 10.9%, 95% CI: 9.9 - 11.9) versus 7.0% (95% CI: 6.7 - 7.3) in controls. The 1-year cumulative incidence of hospitalization for infection was 22.9% (95% CI: 22.1 - 23.8) in AIHA (in primary AIHA: 20.9%, 95% CI: 19.8 - 22.0) versus 3.5% (95% CI: 3.3 - 3.6) in controls. The 5-year cumulative incidence of hospitalization for infection was 37.5% (95% CI: 36.4 - 38.6) in AIHA (in primary AIHA: 33.7%, 95% CI: 32.2 - 35.1) versus 13.5% (95% CI: 13.1 - 13.9) in controls. Conclusion The incidence of AIHA (primary or secondary) was more than ten times higher in the elderly and very elderly as compared with people <50 year-old, suggesting a potential role for immunosenescence. As compared with the general population, AIHA patients had an increased risk of death, hospitalization for infection and thrombosis. It was similar in primary and secondary AIHA. Disclosures Moulis: Grifols: Research Funding; Amgen: Other: meeting attendance grant; Novartis SAS: Membership on an entity's Board of Directors or advisory committees, Other: meeting attendance grant, Research Funding.

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Treatment and Lifestyle Risk Factors for Cardiovascular Disease Post Lymphoma Diagnosis: A Prospective Study in the Modern Treatment Era

Blood ◽

10.1182/blood-2019-127203 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 422-422

Author(s):

Nicholas J Boddicker ◽

Matthew J. Maurer ◽

Melissa C Larson ◽

Cristine Allmer ◽

Susan L. Slager ◽

...

Keyword(s):

Risk Factors ◽

Board Of Directors ◽

Cumulative Incidence ◽

Medical Records ◽

Research Funding ◽

Cardiac Risk ◽

Advisory Committees ◽

Increased Risk ◽

Modern Treatment ◽

New Onset

Background With lymphoma survival rates increasing and a growing population of long-term survivors, the development of cardiovascular disease (CVD) in this patient population is of increasing importance. Anthracyclines are critical in the management of many lymphoma subtypes. However, there is a risk of developing anthracycline-induced CVD. Here, we estimate the cumulative incidence of CVD in adult lymphoma survivors and investigate risk factors associated with post diagnosis CVD. Methods Participants were from the Mayo component of the Molecular Epidemiology Resource (MER) of the University of Iowa/Mayo Clinic Lymphoma Specialized Program of Research Excellence (SPORE). From 2002-2015, the MER offered enrollment to all patients with newly diagnosed lymphoma who are US residents and age >18 years. Participants completed a risk factor questionnaire, and clinical and treatment data were abstracted from medical records. Patients were contacted every 6 months for the first 3 years after diagnosis and annually thereafter to assess disease status, re-treatment and new onset morbidity including CVD. CVD events, including congestive heart failure (CHF), coronary artery disease (CAD), valvular heart disease (VHD), and arrhythmia were identified and validated against medical records. CHF was validated with the Cardiovascular Health Study Criteria and/or the Framingham Criteria. CAD, arrhythmia, and VHD were validated using clinical definitions. We calculated the cumulative incidence of CVD, with death modeled as a competing risk. The association of risk factors and treatments with risk of CVD was estimated using hazard ratios (HR) and 95% confidence intervals (CI) from Cox regression with a competing risk of death. Risk factors included age, sex, diabetes, smoking, body mass index (BMI), and treatment with anthracyclines or radiation therapy. Results The study consisted of 3,063 lymphoma patients after excluding those with chronic lymphocytic leukemia and CVD prior to lymphoma diagnosis. The median age at diagnosis was 59 years (range 18-95), and 56% were males. At a median follow-up was 6.9 years (range 0.8-17.1), 640 patients (21%) had died without CVD and 485 patients self-reported CVD post lymphoma diagnosis, of which 280 (57.7%) were validated. Cardiovascular events included 86 CHF, 78 CAD, 40 VHD, and 164 arrhythmias. The cumulative incidence of CVD (Figure 1) at 5 and 10 years was 6.0% (95% 5.2%-7.0%) and 10.7% (95% CI 9.5%-12.1%), respectively. In multivariable analysis, increasing age (HR=3.93 per 5 years, p<0.001), male sex (HR=1.33, p=0.03), former smoker (HR=1.04, p=0.77), current smoker (HR=1.96, p<0.001), BMI>30 kg/m2 (HR=1.50, p=0.01), and anthracycline treatment (HR=1.49. p<0.001) were all significantly associated with risk of overall CVD, while there was no association with diabetes (HR=0.92, p=0.70) or radiation therapy (HR=1.05, p=0.78) in the multivariable model. Anthracycline use was significantly associated with increased risk of CHF (HR=2.64, p<0.001) and arrhythmia (HR=1.51, p<0.01), but not VHD (HR=0.83, p=0.56) or CAD (HR=1.23, p=0.31) after adjustment for the cardiac risk factors. The number of anthracycline cycles ranged from 0 to 12. 63.2% of individuals that received anthracyclines received 6 cycles. The 5-year cumulative incidence of CVD for 0, 1-5, 6, and >6 anthracycline cycles was 5%, 6.9%, 7.4%, and 7.7%, respectively. Adjusting for cardiac risk factors, the number of anthracycline cycles was significantly associated with increased risk of CVD (1-5 cycles HR=1.34, p=0.11; 6 cycles HR=1.51, p<0.01; >6 cycles HR=2.04, p=0.03). Furthermore, the number of anthracycline cycles was associated with CHF (1-5 cycles HR=2.82, p<0.001; 6 cycles HR=2.46, p<0.001; >6 cycles HR=5.33, p<0.001) and arrhythmia (1-5 cycles HR=1.31, p=0.27; 6 cycles HR=1.60, p<0.01; >6 cycles HR=1.65, p=0.27). Conclusions In the modern treatment era, the risk of new onset CVD in patients with lymphoma without a history of CVD is approximately 1% per year after diagnosis. Arrhythmia and CHF were the most commonly occurring CVD events in this cohort. Both traditional CVD risk factors and treatment with anthracyclines was associated with an increased risk of developing CVD, and anthracyclines were a risk factor for arrhythmia and CHF in particular. Prevention of CVD in lymphoma patients will need to address both treatment and traditional lifestyle factors. Figure 1 Disclosures Maurer: Morphosys: Membership on an entity's Board of Directors or advisory committees; Nanostring: Research Funding; Celgene: Research Funding. Nowakowski:Selvita: Membership on an entity's Board of Directors or advisory committees; Genentech, Inc.: Research Funding; F. Hoffmann-La Roche Ltd: Research Funding; Curis: Research Funding; Bayer: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; NanoString: Research Funding; MorphoSys: Consultancy, Research Funding. Cerhan:NanoString: Research Funding; Celgene: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees.

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Cumulative incidence and risk factors for radiation induced leukoencephalopathy in high grade glioma long term survivors

Scientific Reports ◽

10.1038/s41598-021-89216-1 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Robert Terziev ◽

Dimitri Psimaras ◽

Yannick Marie ◽

Loic Feuvret ◽

Giulia Berzero ◽

...

Keyword(s):

Risk Factors ◽

Cumulative Incidence ◽

High Grade Glioma ◽

High Grade ◽

Nucleotide Polymorphisms ◽

Increased Risk ◽

Radiation Induced ◽

Long Term Survivors

AbstractThe incidence and risk factors associated with radiation-induced leukoencephalopathy (RIL) in long-term survivors of high-grade glioma (HGG) are still poorly investigated. We performed a retrospective research in our institutional database for patients with supratentorial HGG treated with focal radiotherapy, having a progression-free overall survival > 30 months and available germline DNA. We reviewed MRI scans for signs of leukoencephalopathy on T2/FLAIR sequences, and medical records for information on cerebrovascular risk factors and neurological symptoms. We investigated a panel of candidate single nucleotide polymorphisms (SNPs) to assess genetic risk. Eighty-one HGG patients (18 grade IV and 63 grade III, 50M/31F) were included in the study. The median age at the time of radiotherapy was 48 years old (range 18–69). The median follow-up after the completion of radiotherapy was 79 months. A total of 44 patients (44/81, 54.3%) developed RIL during follow-up. Twenty-nine of the 44 patients developed consistent symptoms such as subcortical dementia (n = 28), gait disturbances (n = 12), and urinary incontinence (n = 9). The cumulative incidence of RIL was 21% at 12 months, 42% at 36 months, and 48% at 60 months. Age > 60 years, smoking, and the germline SNP rs2120825 (PPARg locus) were associated with an increased risk of RIL. Our study identified potential risk factors for the development of RIL (age, smoking, and the germline SNP rs2120825) and established the rationale for testing PPARg agonists in the prevention and management of late-delayed radiation-induced neurotoxicity.

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Abstract 13315: Long-term Risk of Cardiovascular Events Following Hospitalization for Sepsis: A Systematic Review and Meta-analysis

Circulation ◽

10.1161/circ.142.suppl_3.13315 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Leah B Kosyakovsky ◽

Federico Angriman ◽

Emma Katz ◽

Neill Adhikari ◽

Lucas C Godoy ◽

...

Keyword(s):

Systematic Review ◽

Cumulative Incidence ◽

Meta Analysis ◽

Hazard Ratios ◽

Increased Risk ◽

Significant Difference ◽

Sepsis Survivors ◽

Risk Ratios

Introduction: Sepsis results in dysregulated inflammation, coagulation, and metabolism, which may contribute to increased cardiovascular disease (CVD) risk. We conducted a systematic review and meta-analysis to determine the association between sepsis and subsequent long-term CVD events. Methods: MEDLINE, Embase, and the Cochrane Controlled Trials Register and Database of Systematic Reviews were searched from inception to May 2020 to identify observational studies of adult sepsis survivors (defined by diagnostic codes or consensus definitions) measuring long-term CV outcomes. The primary outcome was a composite of myocardial infarction, CV death, and stroke. Random-effects models estimated the pooled cumulative incidence and adjusted hazard ratios of CV events relative to hospital or population controls. Odds ratios were included as risk ratios assuming <10% incidence in non-septic controls, and risk ratios were taken as hazard ratios (HR) assuming no censoring. Outcomes were analyzed at maximum follow-up (primary analysis) and stratified by time (<1 year, 1-2 years, and >2 years) since sepsis. Results: Of 11,235 abstracts screened, 25 studies (22 cohort studies, 2 case-crossover studies, and 1 case-control) involving 1,949,793 sepsis survivors were included. The pooled cumulative incidence of CVD events was 9% (95% CI; 5-14%). Sepsis was associated with an increased risk (HR 1.59, 95% CI 1.37-1.86) of CVD events at maximum follow-up ( Figure ); between-study heterogeneity was substantial (I 2 =97.3%). There was no significant difference when comparing studies using population and hospital controls. Significantly elevated risk was observed up to 5 years following sepsis. Conclusions: Sepsis survivors experience an approximately 50% increased risk of CVD events, which may persist for years following the index episode. These results highlight a potential unmet need for early cardiac risk stratification and optimization in sepsis survivors.

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Non-Myeloablative Conditioning Regimen before T-Cell Replete Haploidentical Transplantation with Post-Transplant Cyclophosphamide for Advanced Lymphoma

Blood ◽

10.1182/blood-2019-128004 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 4614-4614

Author(s):

Catalina Montes De Oca ◽

Thomas Pagliardini ◽

Stefania Bramanti ◽

Sabine Furst ◽

Jean Marc Schiano de Collela ◽

...

Keyword(s):

Research Funding ◽

Chronic Gvhd ◽

Disease Status ◽

Research Support ◽

Myeloablative Conditioning ◽

Term Survival ◽

Gvhd Prophylaxis ◽

Increased Risk ◽

Low Incidence

Introduction: allogeneic transplantation (allo-HSCT) is a curative treatment for patients with advanced lymphoma. Haploidentical (haplo-SCT) transplantation extended the accessibility to allo-HSCT, overcoming the issue of donor availability. However, alternative donor allo-HSCT is still considered at higher risk of non-relapse mortality due to the HLA disparity and thus an anticipated higher incidence of GVHD. In this context, the use of a non myeloablative conditioning (NMAC) regimen combined with post transplantation cyclophosphamide (PT-Cy) based GVHD prophylaxis may reduce procedure related toxicity. The aim was to evaluate the toxicity and efficacy of haplo-SCT using NMAC with PT-Cy in advanced lymphoma patients. Methods: We here report the retrospective experience of a bicentric transplantation program. We analyzed a cohort of lymphoma patients undergoing Haplo-SCT and homogeneously receiving NMAC and PT-Cy. Inclusion criteria were: 1) first allo-HSCT for advanced lymphoma between 2009 and 2018; 2) haploidentical donor; 3) NMAC (fludarabine cyclophosphamide and 2 gray TBI GVHD prophylaxis consisted of PT-Cy day+3 and +4 , cyclosporine A and MMF starting from day +5. Multivariate analyses included age, disease type (NHL vs HL), HCT-CI (< vs ≥ 3), graft source (PBSC vs BM), disease status at haplo-SCT (CR vs other). Results: One hundred forty seven patients (73 NHL; 74 HL) with a median age of 46 years (range: 19-71) were included. PBSC (peripheral blood stem cell) was used as graft source in 96 patients (65%). Patients received a median number of 3 conventional chemotherapy lines before haplo-SCT (1-8). Sixty-five (44%) had relapse after Auto-HCT. At the time of haplo-SCT, 96 patients (66%) were in complete remission. The cumulative incidences of day+100 grade 2-4 and 3-4 acute GVHD were 30% and 3%, respectively. The cumulative incidences of 2-year chronic and moderate or severe chronic GVHD were 13% and 8%, respectively. With a median follow up of 39 months (6-114), 2-year NRM was 14%, with a trend for higher risk in patients with HCT-CI ≥ 3 (HR 0.39, 95CI [0.15-1.04] p = 0.061) while age was not associated with an increased risk of NRM (HR 1.01, 95CI [0.98-1.05], p = 0.450). Two-year cumulative incidence of relapse (CIR) was 21% and 18% in HL and NHL patients, respectively. Disease status at the time of haplo-SCT was strongly associated with relapse (HR 2.99, 95CI [1.41-6.35], p = 0.004) In HL patients, 2-year PFS, OS and GRFS were 65%, 77% and 57%, respectively, while corresponding values in NHL patients were 65%, 69% and 55%, respectively. Two-year PFS and GRFS were significantly higher in patients who underwent haplo-SCT in CR (PFS: CR vs. no CR: 72% vs. 55%, p=0.045; GRFS: CR vs. no CR: 63% vs. 42%, p=0.010). There was a trend for better 2-year OS in CR (OS: CR vs. no CR: 78% vs. 63%, p=0.063. Conclusion: We confirm the feasibility of haplo-SCT using NMAC and PT-Cy with low incidence of GVHD (notably severe forms) and NRM. In addition, we observed a relatively low incidence of relapse (19%) in this cohort of heavily pretreated patients, underlining a potent graft-versus-lymphoma effect after haplo-SCT, leading to promising survivals, including high rate of GRFS (>50%), suggesting a preserved long term quality of life in survivors. We conclude that NMAC haplo-SCT with PT-Cy should be considered as a valuable curative option for advanced lymphoma patients, with a favorable toxicity profile and promising long term survival. Figure Disclosures Stoppa: celgene: Other: travel fees, lecture fees; takeda: Other: travel fees. Carlo-Stella:MSD: Honoraria; BMS: Honoraria; Janssen: Other: Travel, accommodations; Boehringer Ingelheim: Consultancy; Genenta Science sr: Consultancy; Sanofi: Consultancy, Research Funding; ADC Therapeutics: Consultancy, Other: Travel, accommodations, Research Funding; Novartis: Consultancy, Research Funding; Servier: Consultancy, Honoraria, Other: Travel, accommodations; F. Hoffmann-La Roche Ltd: Honoraria, Other: Travel, accommodations, Research Funding; Rhizen Pharmaceuticals: Research Funding; Celgene: Research Funding; Amgen: Honoraria; Takeda: Other: Travel, accommodations; Janssen Oncology: Honoraria; AstraZeneca: Honoraria. Chabannon:EBMT: Other: Working Party Chair, Board member; Fresenius Kabi: Other: research support; Miltenyi Biotech: Other: research support; Terumo BCT: Other: speaker's fees; Celgene: Other: speaker's fees; Novartis: Other: speaker's fees; Gilead: Other: speaker's fees, hospitalities; Sanofi SA: Other: research support, speaker's fees, hospitalities. Santoro:Takeda: Speakers Bureau; BMS: Speakers Bureau; Roche: Speakers Bureau; Abb-Vie: Speakers Bureau; Amgen: Speakers Bureau; Celgene: Speakers Bureau; Servier: Consultancy, Speakers Bureau; Gilead: Consultancy, Speakers Bureau; AstraZeneca: Speakers Bureau; Pfizer: Consultancy, Speakers Bureau; Arqule: Consultancy, Speakers Bureau; Lilly: Speakers Bureau; Sandoz: Speakers Bureau; Eisai: Consultancy, Speakers Bureau; Novartis: Speakers Bureau; Bayer: Consultancy, Speakers Bureau; MSD: Speakers Bureau; BMS: Consultancy. Blaise:Sanofi: Honoraria; Jazz Pharmaceuticals: Honoraria; Molmed: Consultancy, Honoraria; Pierre Fabre medicaments: Honoraria.

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Chronic Health Conditions and Late Mortality Among Survivors of Childhood Acute Myeloid Leukemia: A Report from the Childhood Cancer Survivor Study (CCSS)

Blood ◽

10.1182/blood-2019-123477 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 1315-1315

Author(s):

Lucie M Turcotte ◽

John A Whitton ◽

Wendy M. Leisenring ◽

Todd Gibson ◽

Rebecca M Howell ◽

...

Keyword(s):

Cumulative Incidence ◽

Myeloid Leukemia ◽

Health Conditions ◽

Late Mortality ◽

Treatment Groups ◽

Childhood Acute Myeloid Leukemia ◽

Health Related ◽

Related Mortality

Introduction: Five-year survival following childhood acute myeloid leukemia (AML) has doubled over the last 4 decades due to advances in treatment and supportive care, including more widespread use of hematopoietic cell transplantation (HCT). The impact on long-term morbidity and mortality among survivors is unknown. Methods: Cumulative incidence and 95% confidence intervals (CI) for overall and cause-specific late (>5 years from diagnosis) mortality and CTCAE grades 3-5 chronic health conditions (CHC) were estimated among 5-year survivors of AML diagnosed <21 years of age between1970-99 in the CCSS. Comparisons were made by decade of diagnosis (1970s, 1980s, 1990s) and treatment (HCT vs. chemotherapy only [chemo-only]). Cox regression models estimated hazard ratios (HR) for health-related deaths and CHC based on treatment decade and HCT status. Results: Among 927 AML survivors (median age at diagnosis 7.1 years [range 1-21 years]; median age at last follow-up 29.4 years [range 8-60 years]; 16,069 person-years of follow-up; 37% treated with HCT [15% of 1970s survivors, 36% of 1980s survivors, 44% of 1990s survivors), the 20-year cumulative incidence of all-cause mortality was 6.7% (CI 4.2-9.2%) for chemo-only survivors and 13.5% (CI 9.2-17.8%) for HCT survivors. For chemo-only survivors, the highest incidence of health-related mortality were attributable to cardiac causes (1.5%, CI 0.5-2.6), relapse (0.9%, CI 0.1-1.8), and SMN (0.6%, CI 0.0-1.2), whereas for HCT survivors the highest health-related causes of death were relapse (6.5%, CI 3.7-9.2%), SMN (1.3%, CI 0-2.5%), and pulmonary causes (0.6%, CI 0-1.5%). When treatment groups were considered in multivariable Cox models, risk for late mortality was similar for chemo-only survivors from the 1990s compared to the 1970s (HR 0.4, CI 0.1-1.4), but risk was reduced for HCT survivors from the 1990s compared to the 1970s (HR 0.2, CI 0.1-0.4). The 20-year cumulative incidence of grade 3-5 CHCs among chemo-only survivors was 26.9% (CI 23.0-30.7%) compared to 46.8% (CI 40.9-52.7%) among HCT survivors, with the highest incidence occurring for cardiovascular CHC (chemo-only, 9.7%, CI 7.1-12.2%; HCT, 10.6%, CI 7.0-14.2%), pulmonary CHC (chemo-only, 1.0%, CI 0.1-1.9%; HCT, 2.9%, CI 1.0-4.8%) and SMN (chemo-only, 0.8%, CI 0.0-1.7%; HCT, 5.7%, CI 2.9-8.6%). Incidence of overall CHC decreased in more recent decades among HCT survivors (p=0.03, Figure); however, among chemo-only survivors, CHC incidence did not significantly change by decade (p=0.12). When treatment groups were considered in adjusted models, risk for CHC was similar for those treated in the 1990s compared to the 1970s among chemo-only survivors (HR 1.5, CI 1.0-2.3) and risk estimates among HCT survivors decreased over time but did not achieve statistical significance (HR 0.6, CI 0.3-1.1). Conclusions: AML survivors treated with HCT had a reduced risk of late mortality and serious CHC in more recent treatment eras. In contrast, treatment with chemo-only was not associated with differences in mortality and serious CHC risk over time. Five-year survivors treated with chemo-only had a significantly reduced risk of health-related mortality compared with HCT survivors across all treatment eras. While treatment intensification with HCT has improved the cure rates for AML in recent decades, there remains disparity in long-term outcomes among AML survivors treated with HCT vs. chemo-only. Disclosures No relevant conflicts of interest to declare.

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Cardiac Morbidity in Adolescents and Young Adult Survivors of Hodgkin Lymphoma

Blood ◽

10.1182/blood-2020-136454 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 18-19

Author(s):

Kristin C. Marr ◽

Jonathan Simkin ◽

Andrea C. Lo ◽

Joseph M. Connors ◽

Alina S. Gerrie ◽

...

Keyword(s):

Cumulative Incidence ◽

Research Funding ◽

Index Date ◽

Population Based ◽

Stage Disease ◽

Increased Risk ◽

Matched Case ◽

Cv Disease ◽

Relapsed Disease

INTRODUCTION Adolescents and young adult (AYA) survivors of Hodgkin lymphoma (HL) are potentially at increased risk of cardiovascular (CV) disease due to anthracycline exposure, in addition to use of mediastinal radiotherapy (RT). Although the risk has been well described in the pediatric age-group, the impact in the AYA population has been less well characterized. Capturing the incidence of these late effects is challenging given that events can occur more than a decade after therapy completion. Using population-based administrative data, we evaluated the incidence of CV disease (combined heart failure (HF) and ischemic heart disease (IHD)) in a cohort of AYA survivors treated for classical HL (cHL) using ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) or equivalent chemotherapy. METHODS Patients with cHL aged 16-39 years (y), diagnosed between 1992-2013 and treated with an ABVD or equivalent therapy, were identified in the BC Cancer Lymphoid Cancer Database. Patients must have survived to an Index Date defined as 2 y from most recent HL event (primary diagnosis or if applicable, most recent relapse) and have had a minimum follow-up of 1 y beyond their Index Date. Patients were excluded if they had history of prior malignancy or HIV positivity. Limited stage disease was defined as stage IA, IB or IIA and absence of bulky disease (≥10cm); all others had advanced stage disease. Cases were linked with population-based databases of BC Cancer Registry; BC Radiation Oncology Database; and BC Ministry of Health (MOH) Chronic Disease Registry (CDR) that captures all BC residents registered with medical service plan coverage during the study period. The outcome variables, including HF and IHD, were defined by the BC MOH CDR using Standardized Case Definitions. To focus on late onset CV complications, only events that occurred after the Index Date were included in the analysis. A 10:1 individually-matched control population was identified from the CDR based on age, sex, and health authority region on the Index Date of the matched case. Controls were excluded if they had a pre-existing malignancy, HF, or IHD prior to the study window. Individual outcomes were collected from the Index Date of the matched case until December 31, 2015 or until an individual was censored due to loss to follow-up or death. Kaplan Meier (K-M) methodology and log-rank test was used to estimate cumulative incidence. A competing risk regression analysis was used to evaluate relative risk (RR) and p-values less than 0.05 were considered significant. RESULTS With a median follow-up time of 11 y (range 3-24 y) from most recent HL event, 764 AYA 2-y survivors were identified, aged 20 to 61 y (median 38 y) at the end of study period. The proportion of limited and advanced stage disease was 34.2% and 65.6%, respectively; and 49.9% were male. Eighty-eight patients (11.5%) had relapsed disease; eighty-six (11.3%) underwent high dose chemotherapy and autologous stem cell transplantation as part of their salvage therapy. In total, 268 patients (36.4%) were treated with mediastinal RT for primary therapy or for relapsed disease. Fifty-three percent received cumulative anthracycline dose ≥300 mg/m2. Survivors had a 3-fold increased risk of CV disease relative to controls (p<0.0001). The onset of CV disease in survivors occurred at median of 11.7 y after most recent treatment (range 2.2-19.2 y), and at a median age of 44.3 y (range 21 - 58 y). At 15 y, the estimated cumulative incidence of CV disease was 6.3% in survivors compared to 2.3% in controls (Figure A). In the 496 survivors that received chemotherapy only, the incidence of CV disease at 15 y was 4.6% vs 2.3% in controls, and those that received anthracyclines and mediastinal RT had significantly higher incidence at 8.6% (Figure B). The increase in risk was greatest for a diagnosis of HF (RR 6.92, p<0.0001): at 15 y, the cumulative incidence of HF was 2.2% vs 0.6% in controls. The RR of IHD was 2.63 (p<0.0001) with incidence of 5.1% in cases compared to 1.8% in controls. CONCLUSION Similar to the pediatric population, AYA cHL survivors are at increased risk of both HF and IHD after completion of treatment. The majority of patients had received ABVD alone and had a lower incidence of CV disease at 15 y when compared to those that received treatment that included mediastinal RT. These results will inform counseling regarding risk factor modification and aid in the development of surveillance guidelines for AYA survivors. Disclosures Gerrie: Sandoz: Consultancy; Roche: Research Funding; Janssen: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Research Funding; Astrazeneca: Consultancy, Research Funding. Villa:Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Roche: Consultancy, Honoraria, Research Funding; AZ: Consultancy, Honoraria, Research Funding; Kite/Gilead: Consultancy, Honoraria; Nano String: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; Sandoz Canada: Consultancy, Honoraria; Immunovaccine: Consultancy, Honoraria; Purdue Pharma: Consultancy, Honoraria. Scott:NIH: Consultancy, Other: Co-inventor on a patent related to the MCL35 assay filed at the National Institutes of Health, United States of America.; Roche/Genentech: Research Funding; Celgene: Consultancy; NanoString: Patents & Royalties: Named inventor on a patent licensed to NanoString, Research Funding; Abbvie: Consultancy; AstraZeneca: Consultancy; Janssen: Consultancy, Research Funding. Sehn:AstraZeneca: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Kite: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Genentech, Inc.: Consultancy, Honoraria, Research Funding; Acerta: Consultancy, Honoraria; F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Research Funding; MorphoSys: Consultancy, Honoraria; Merck: Consultancy, Honoraria; Lundbeck: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; Teva: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria; Servier: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria; Apobiologix: Consultancy, Honoraria; Verastem Oncology: Consultancy, Honoraria; TG therapeutics: Consultancy, Honoraria; Chugai: Consultancy, Honoraria. Savage:BeiGene: Other: Steering Committee; Roche (institutional): Research Funding; Merck, BMS, Seattle Genetics, Gilead, AstraZeneca, AbbVie, Servier: Consultancy; Merck, BMS, Seattle Genetics, Gilead, AstraZeneca, AbbVie: Honoraria.

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Occurrence of Multiple Subsequent Neoplasms in Long-Term Survivors of Childhood Cancer: A Report From the Childhood Cancer Survivor Study

Journal of Clinical Oncology ◽

10.1200/jco.2011.34.6585 ◽

2011 ◽

Vol 29 (22) ◽

pp. 3056-3064 ◽

Cited By ~ 102

Author(s):

Gregory T. Armstrong ◽

Wei Liu ◽

Wendy Leisenring ◽

Yutaka Yasui ◽

Sue Hammond ◽

...

Keyword(s):

Childhood Cancer ◽

Cumulative Incidence ◽

Malignant Neoplasm ◽

Childhood Cancer Survivors ◽

Late Morbidity ◽

Childhood Cancer Survivor Study ◽

Survivors Of Childhood Cancer ◽

Long Term Survivors

Purpose Childhood cancer survivors experience an increased incidence of subsequent neoplasms (SNs). Those surviving the first SN (SN1) remain at risk to develop multiple SNs. Because SNs are a common cause of late morbidity and mortality, characterization of rates of multiple SNs is needed. Patients and Methods In a total of 14,358 5-year survivors of childhood cancer diagnosed between 1970 and 1986, analyses were carried out among 1,382 survivors with an SN1. Cumulative incidence of second subsequent neoplasm (SN2), either malignant or benign, was calculated. Results A total of 1,382 survivors (9.6%) developed SN1, of whom 386 (27.9%) developed SN2. Of those with SN2, 153 (39.6%) developed more than two SNs. Cumulative incidence of SN2 was 46.9% (95% CI, 41.6% to 52.2%) at 20 years after SN1. The cumulative incidence of SN2 among radiation-exposed survivors was 41.3% (95% CI, 37.2% to 45.4%) at 15 years compared with 25.7% (95% CI, 16.5% to 34.9%) for those not treated with radiation. Radiation-exposed survivors who developed an SN1 of nonmelanoma skin cancer (NMSC) had a cumulative incidence of subsequent malignant neoplasm (SMN; ie, malignancies excluding NMSC) of 20.3% (95% CI, 13.0% to 27.6%) at 15 years compared with only 10.7% (95% CI, 7.2% to 14.2%) for those who were exposed to radiation and whose SN1 was an invasive SMN (excluding NMSC). Conclusion Multiple SNs are common among aging survivors of childhood cancer. SN1 of NMSC identifies a population at high risk for invasive SMN. Survivors not exposed to radiation who develop multiple SNs represent a population of interest for studying genetic susceptibility to neoplasia.

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Examining the relationship between sepsis and oropharyngeal dysphagia in hospitalised elderly patients: a retrospective cohort study

Frontline Gastroenterology ◽

10.1136/flgastro-2018-100994 ◽

2018 ◽

Vol 9 (4) ◽

pp. 256-261 ◽

Cited By ~ 1

Author(s):

Ayodele Sasegbon ◽

Laura O’Shea ◽

Shaheen Hamdy

Keyword(s):

Risk Factors ◽

Elderly Patients ◽

Elderly Person ◽

Oropharyngeal Dysphagia ◽

The Elderly ◽

Common Source ◽

Increased Risk ◽

The Mean ◽

The Relationship ◽

New Onset

IntroductionElderly people are recognised to be at increased risk of oropharyngeal dysphagia (OPD), the causes of which are multifactorial. Our aim was to identify if sepsis is associated with OPD in the elderly during hospitalisation in the absence of known other risk factors for OPD.MethodsA hospital electronic database was searched for elderly patients (≥65 years) referred for assessment for suspected dysphagia between March 2013 and 2014. Exclusion criteria were age <65 years, pre-existing OPD or acute OPD secondary to acute intracranial event, space-occupying lesion or trauma. Data were collected on factors including age, sex, comorbidities, existing OPD, sepsis, microbiology, recovery of OPD and medication. Sepsis was defined as evidence of a systemic inflammatory response syndrome with a clinical suspicion of infection.ResultsA total of 301 of 1761 screened patients referred for dysphagia assessment met the inclusion criteria. The prevalence of sepsis and subsequent OPD was 16% (51/301). The mean age was 83 years (median 81 years). The most common comorbidity was dementia (31%). The majority (84%) failed to recover swallowing during their hospital stay, 12% had complications of aspiration and 35% died. The most common source of sepsis was from the chest (55%). Other factors contributing to the risk for dysphagia included delirium (22%) and neuroactive medication (41%). However, 10% of patients had sepsis and subsequent OPD without other identified risk factors.ConclusionThe prevalence of sepsis and subsequent dysphagia is significant and should be taken into account in any elderly person in hospital with new-onset OPD without other predisposing risk factors.

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