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

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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Second Malignancies After Autologous Hematopoietic Cell Transplantation (AHCT) for Multiple Myeloma (MM): A Center for International Blood and Marrow Transplant Research (CIBMTR) Analysis

Blood ◽

10.1182/blood.v120.21.591.591 ◽

2012 ◽

Vol 120 (21) ◽

pp. 591-591

Author(s):

Girindra Raval ◽

Anuj Mahindra ◽

Xiaobo Zhong ◽

Ruta Brazauskas ◽

Robert Peter Gale ◽

...

Keyword(s):

Risk Factors ◽

At Risk ◽

Multivariate Analysis ◽

General Population ◽

Cumulative Incidence ◽

Incidence Rates ◽

High Dose ◽

Risk Of Death ◽

Age And Sex

Abstract Abstract 591 Background: Survival of patients with MM has improved over the past two decades, in part due to the use of AHCT. Increasingly, second primary malignancies (SPMs) are observed in MM survivors. Determining the baseline incidence and risk factors associated with SPMs after AHCT is important to assess risk and to evaluate the risk-benefit ratio of newer therapies. Methods: We analyzed the incidence of SPMs in 3784 MM patients receiving (“upfront”) AHCT for MM within 18 months of diagnosis between 1990 and 2010 and reported to the CIBMTR. Cumulative incidence rates of SPMs were estimated taking into account the competing risk of death. For each transplant recipient, the number of person-years at risk was calculated from the date of transplantation until date of last contact, death, or diagnosis of SPM, whichever occurred first. Incidence rates for all invasive cancers in the general population were obtained from the SEER database. Age-, sex-, and race- specific incidence rates for overall SPMs and particular anatomical sites were applied to the appropriate person-years at risk to compute the expected numbers of cancers. Observed–to –expected (O/E) ratios were calculated, and Poisson distribution 99% confidence intervals (CIs) were generated. Poisson regression model was used to analyze risk factors for overall SPMs and AML/MDS. Results: Pre-transplant therapy included novel agents in 56% including thalidomide (35%), lenalidomide (9%), bortezomib (16%) or their combinations (11%). Majority (80%) received high dose melphalan conditioning. Post-transplant maintenance therapy included thalidomide (16%), lenalidomide (8%), bortezomib (9%) and interferon (6%). Median follow-up of survivors was 52 months (range 3 to 192 months).With 12707 person years of follow up, 153 new malignancies were reported with a crude rate of 1.2 SPM per 100 person years of follow up. Observed/Expected [O/E] ratio for all SPMs was 0.99 (99% CI, 0.80–1.22). Cumulative incidence of SPM overall was 2.48% (95% CI, 1.96–3.05) at 3 years and 6.0% (95% CI, 4.96–7.10) at 7 years [Figure 1]. Individual SPMs observed significantly more frequently than expected are summarized in Table 1. The cumulative incidence of MDS/AML was 0.5% (95% CI, 0.28–0.78) at 3 years and 1.3 (95% CI, 0.85– 1.9%) at 7 years. Majority had MM progression prior to diagnosis of SPM (65 of 102 patients overall and 15 of 23 patients for MDS/AML). In multivariate analysis, significant risk factors for development of SPMs included: obesity [Hazard ratio = HR 1.89(95%CI, 1.21–2.93), p=0.0047 for BMI>30 vs. BMI<25], older age: [HR10.53 (95%CI, 1.46–75.82), p=0.0195] for 60–69 year olds and HR14.4 (95%CI, 1.89–109.75), p=0.01 for 70+ year olds compared to the 18–39 year old group. Specific conditioning regimens did not correlate with the risk of SPM. The low number of MDS/AML (33 events out of 3784 cases) limited the power of multivariate analysis. Increasing age was significantly associated with development of MDS (HR10.77, (95%CI,92.09–55.51), p=0.004 for 70+ year old vs. 40–49 year olds). Conclusion: In this large cohort of AHCT recipients for MM, the incidence of MDS/AML, melanoma and other skin cancers was significantly higher compared to age and sex matched general population. However the overall risk of SPM was similar to that expected for age and sex matched population. It was also similar to the placebo arms of recent reports by McCarthy Pl et al and Attal M et al (N Engl J Med. 10; 366(19):1770–91). Lenalidomide (8%) or thalidomide maintenance (16%) used in a small subset of patients with comparatively short follow up, was not associated with risk of SPM in the analysis of the overall cohort. Disclosures: Gale: Celgene: Employment. Brandenburg:Celgene: Employment, Equity Ownership. Lonial:Millennium, Celgene, Novartis, BMS, Onyx, Merck all Consultancy. Krishnan:Celgene and Millennium: Consultancy, Speakers Bureau. Dispenzieri:Celgene and Millennium: Research Funding. Hari:Celgene: Consultancy, Honoraria.

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Risk of New Cancers After Radiotherapy in Long-Term Survivors of Retinoblastoma: An Extended Follow-Up

Journal of Clinical Oncology ◽

10.1200/jco.2005.05.054 ◽

2005 ◽

Vol 23 (10) ◽

pp. 2272-2279 ◽

Cited By ~ 308

Author(s):

Ruth A. Kleinerman ◽

Margaret A. Tucker ◽

Robert E. Tarone ◽

David H. Abramson ◽

Johanna M. Seddon ◽

...

Keyword(s):

Cumulative Incidence ◽

Tumor Registry ◽

Risk Of Death ◽

Medical Centers ◽

New Information ◽

Increased Risk ◽

Long Term Survivors ◽

The Brain

Purpose Many children diagnosed with retinoblastoma (Rb) survive into adulthood and are prone to subsequent cancers, particularly hereditary patients, who have germline Rb-1 mutations. We have extended the follow-up of a large cohort of Rb patients for 7 more years to provide new information on the risk of additional cancers after radiotherapy in long-term survivors. Patients and Methods We analyzed the risk of new cancers through 2000 in 1,601 Rb survivors, diagnosed from 1914 to 1984, at two US medical centers. The standardized incidence ratio (SIR) was calculated as the ratio of the observed number of cancers after hereditary and nonhereditary Rb to the expected number from the Connecticut Tumor Registry. The cumulative incidence of a new cancer after hereditary and nonhereditary Rb and radiotherapy was calculated with adjustment for competing risk of death. Results Subsequent cancer risk in 963 hereditary patients (SIR, 19; 95% CI, 16 to 21) exceeded the risk in 638 nonhereditary Rb patients (SIR, 1.2; 95% CI, 0.7 to 2.0). Radiation further increased the risk of another cancer in hereditary patients by 3.1-fold (95% CI, 2.0 to 5.3). Hereditary patients continued to be at significantly increased risk for sarcomas, melanoma, and cancers of the brain and nasal cavities. The cumulative incidence for developing a new cancer at 50 years after diagnosis of Rb was 36% (95% CI, 31% to 41%) for hereditary and 5.7% (95% CI, 2.4% to 11%) for nonhereditary patients. Conclusion Hereditary Rb predisposes to a variety of new cancers over time, with radiotherapy further enhancing the risk of tumors arising in the radiation field.

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Long-Term Cause-Specific Mortality of Patients Treated for Hodgkin’s Disease

Journal of Clinical Oncology ◽

10.1200/jco.2003.07.131 ◽

2003 ◽

Vol 21 (18) ◽

pp. 3431-3439 ◽

Cited By ~ 488

Author(s):

Berthe M.P. Aleman ◽

Alexandra W. van den Belt-Dusebout ◽

Willem J. Klokman ◽

Mars B. van’t Veer ◽

Harry Bartelink ◽

...

Keyword(s):

General Population ◽

Hodgkin's Disease ◽

Hodgkin’S Disease ◽

Initial Therapy ◽

Second Primary ◽

Risk Of Death ◽

Increased Risk ◽

Specific Mortality

Purpose: To assess long-term cause-specific mortality of young Hodgkin’s disease (HD) patients. Patients and Methods: The study population consisted of 1,261 patients treated for HD before age 41 between 1965 and 1987. Follow-up was complete until October 2000. For 95% of deaths, the cause was known. Long-term cause-specific mortality was compared with general population rates to assess relative risk (RR) and absolute excess risk (AER) of death. Results: After a median follow-up of 17.8 years, 534 patients had died (55% of HD). The RR of death from all causes other than HD was 6.8 times that of the general population, and still amounted to 5.1 after more than 30 years. RRs of death resulting from solid tumors (STs) and cardiovascular disease (CVD) were increased overall (RR = 6.6 and 6.3, respectively), but especially in patients treated before age 21 (RR = 14.8 and 13.6, respectively). When these patients grew older, this elevated mortality decreased. The overall AER of death from causes other than HD increased throughout follow-up. Patients receiving salvage chemotherapy had a significantly increased RR of death from STs, compared to patients receiving initial therapy only. Conclusion: The main cause of death among HD patients was lymphoma, but after 20 years, HD mortality was negligible. The RRs and AERs of death from second primary cancers (SCs) and CVDs continued to increase after 10 years. Even more than 30 years after diagnosis, HD patients experienced elevated risk of death from all causes other than HD. Increased risk of death from SCs and CVDs was found especially in patients treated before age 21, but these risks seemed to abate with age.

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Impact of Chronic Graft-Versus-Host Disease on Long-Term Outcomes of Reduced-Intensity Conditioning Allogeneic Hematopoietic Cell Transplantation for Adults with High-Risk Acute Lymphoblastic Leukemia in First Remission

Blood ◽

10.1182/blood.v128.22.3980.3980 ◽

2016 ◽

Vol 128 (22) ◽

pp. 3980-3980

Author(s):

Jae-Ho Yoon ◽

Sung-Soo Park ◽

Young-Woo Jeon ◽

Sung-Eun Lee ◽

Byung-Sik Cho ◽

...

Keyword(s):

High Risk ◽

Board Of Directors ◽

Median Time ◽

Cumulative Incidence ◽

Research Funding ◽

Chronic Gvhd ◽

Unrelated Donor ◽

Advisory Committees

Abstract Background : The role of reduced-intensity conditioning allogeneic hematopoietic cell transplantation (RIC-HCT) in adult acute lymphoblastic leukemia (ALL) remains unclear because the interpretation of transplantation outcome is mainly limited by the small sample size, short follow-up duration, various regimens for conditioning and graft-versus-host disease (GVHD) prophylaxis, and the heterogeneity of the criteria used to select patients for RIC-HCT. Previously, we conducted a phase 2 trial of RIC-HCT in adults with high-risk ALL who were ineligible for myeloablative conditioning and showed the potential role of this strategy, especially in patients in first complete remission (CR1). Here, we report the long-term outcomes of RIC-HCT by analyzing 122 consecutive adults with high-risk ALL in CR1, particularly focusing on the prognostic relevance of chronic GVHD. Methods: During the period between 2000 and 2014, 122 patients in CR1 (median age, 52 years [range, 15-65 years]; 54 Ph-negative ALL and 68 Ph-positive ALL) were given an identical RIC regimen consisting of fludarabine (150 mg/m2 in total) and melphalan (140 mg/m2in total). The indications for RIC-HCT were advanced age (≥50 years; n=79; 64.8%) and comorbid conditions (n=43; 35.2%). Graft sources were peripheral blood stem cells (n=118; 66 matched sibling donor, 23 matched unrelated donor, 29 mismatched unrelated donor) and bone marrow (n=4; 1 matched sibling donor, 1 matched unrelated donor, 2 mismatched unrelated donor). The median time to transplantation was 155.5 days (range, 103-291 days). GVHD prophylaxis was attempted by administering calcineurin inhibitors (cyclosporine for sibling donor transplants, tacrolimus for unrelated donor transplants) plus methotrexate. Antithymocyte globulin was administered to the patients who received mismatched unrelated donor grafts. If residual leukemia was detected in the absence of GVHD at 3 months after transplantation, calcineurin inhibitors were rapidly discontinued. Results: The median time for neutrophil and platelet recovery was 12 days (range, 8-30 days) and 13 days (range, 5-60 days) after RIC-HCT. Sixty-two patients developed acute GVHD (53 grade II, 5 grade III, 4 grade IV). The cumulative incidence of acute GVHD at 1 year was 50.8% (42.6% for Ph-negative and 57.4% for Ph-positive, P=0.152). Except for 11 patients with early deaths within 100 days, 77 developed chronic GVHD (30 mild, 29 moderate, 18 severe), resulting in a 5-year cumulative incidence of 63.6% (69.1% for Ph-negative ALL and 58.8% for Ph-positive ALL, P=0.319). The median time to onset of chronic GVHD was 140 days (range, 37-843 days) after transplantation. Cytomegalovirus reactivation >10,000 copies/mL was observed in 40.2% (44.4% for Ph-negative ALL and 36.8% for Ph-positive ALL, P=0.447). After a median follow-up duration of 57.9 months (range, 17.7-206.8 months), the 5-year cumulative incidence of relapse (CIR) and non-relapse mortality (NRM) were 27.5% (23.9% for Ph-negative ALL and 30.2% for Ph-positive ALL) and 19.0% (17.4% for Ph-negative ALL and 20.3% for Ph-positive ALL), respectively, and the 5-year disease-free survival (DFS) and overall survival (OS) rates were 53.5% (58.4% for Ph-negative ALL and 49.7% for Ph-positive ALL) and 59.8% (60.2% for Ph-negative ALL and 59.3% for Ph-positive ALL). In multivariate analysis, the presence of chronic GVHD lowered CIR (HR, 0.23; 95% CI, 0.10-0.48; P<0.001), but severe chronic GVHD increased NRM (HR, 8.76; 95% CI, 3.39-22.6; P<0.001). Thus, the presence of mild to moderate chronic GVHD was closely related to better outcomes in terms of DFS (HR, 0.45; 95% CI, 0.32-0.64; P<0.001) and OS (HR, 0.44; 95% CI, 0.30-0.64; P<0.001) in all patients as well as in both subgroups of patients. In Ph-positive ALL subgroup of patients, patients without achievement of major molecular response until the time of transplantation had also significantly higher CIR (HR, 7.42; 95% CI, 3.04-18.10; P<0.001) and poorer DFS (HR, 3.47; 95% CI, 1.48-8.14; P=0.004) and OS (HR, 2.58; 95% CI, 1.03-6.47; P=0.043). Conclusion: Our long-term follow-up data with a uniform treatment strategy suggest that RIC-HCT is a valid alternative choice for providing a long-term disease control for adult high-risk ALL patients in CR1. Minimal residual disease-based treatment strategies to reduce leukemia cell burden before HCT and to enhance the graft-versus-leukemia effect are needed in the future. Disclosures Kim: ILYANG: Consultancy, Honoraria, Research Funding; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Lee:Alexion Pharmaceuticals, Inc.: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

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Secondary Malignancies in CML Patients – Data From the German CML Study IV

Blood ◽

10.1182/blood.v120.21.3746.3746 ◽

2012 ◽

Vol 120 (21) ◽

pp. 3746-3746 ◽

Cited By ~ 2

Author(s):

Manuel Barreto Miranda ◽

Michael Lauseker ◽

Ulrike Proetel ◽

Annette Schreiber ◽

Benjamin Hanfstein ◽

...

Keyword(s):

General Population ◽

Confidence Interval ◽

Incidence Rate ◽

Interferon Alpha ◽

Research Funding ◽

Incidence Rates ◽

Primary Cancer ◽

Secondary Malignancies

Abstract Abstract 3746 Introduction: The increase of overall survival in chronic myeloid leukemia (CML) requires closer long-term observation in the face of a potential carcinogenicity of tyrosine kinase inhibitors (TKIs). Preclinical studies with imatinib in rats showed neoplastic changes in kidneys, urinary bladder, urethra, preputial and clitoral glands, small intestine, parathyroid glands, adrenal glands, and nonglandular stomach. Two epidemiologic studies on patients with chronic myeloproliferative neoplasms (CMPN) and CML (Frederiksen H et al., Blood 2011; Rebora P et al., Am J Epidemiol 2010) found an increased risk of secondary malignancies compared with the general population independent of treatment. In contrast, in a recent analysis of patients with CML and CMPN treated with TKI (Verma D et al., Blood 2011) a decreased risk of secondary malignancies was reported. Aims: To further elucidate the risk of TKI treated CML patients for the development of secondary malignancies we analysed data of the CML study IV, a randomized 5-arm trial (imatinib 400 mg vs. imatinib 800 mg vs. imatinib 400 mg in combination with interferon alpha vs. imatinib 400 mg in combination with AraC vs. imatinib 400 mg after interferon failure). Patients and methods: From February 2002 to April 2012, 1551 CML patients in chronic phase were randomized, 1525 were evaluable. Inclusion criteria allowed the history of primary cancer if the disease was in stable remission. Forty-nine malignancies were reported in 43 patients before the diagnosis of CML. If relapses occurred within 5 years after diagnosis of primary cancer they were not considered for further analysis. Median follow-up was 67.5 months. Age-standardized incidence rates were calculated from the age-specific rates using the European standard population (1976). Results: In total, 67 secondary malignancies in 64 patients were found in CML patients treated with TKI (n=61) and interferon alpha only (n=3). Twelve of these patients developed neoplasms after diagnosis of a primary cancer before diagnosis of CML, 5 patients with metastases or recurrence of the first malignancy (range of diagnosis 5–19 years after primary cancer). Median time to secondary malignancy was 2.5 years (range 0.1–8.3 years). The types of neoplasms were: prostate (n=9), colorectal (n=6), lung (n=6), non Hodgkin's lymphoma (NHL; n=7), malignant melanoma (n=5), skin tumors (basalioma n=4 and squamous cell carcinoma n=1), breast (n=5), pancreas (n=4), kidney (n=4), chronic lymphocytic leukemia (n=3), head and neck (n=2), biliary (n=2), sarcoma (n=2), and esophagus, stomach, liver, vulva, uterus, brain, cancer of unknown origin (each n=1). With these numbers the age-standardized incidence rates of secondary malignancies in CML patients were calculated: 534 cases per 100,000 for men (confidence interval [350;718]), and 582 for women (confidence interval [349;817]). The incidence rates of the general population in Germany were 450 and 350 cases, respectively (“Krebs in Deutschland 2007/2008”, 8th ed., Robert Koch Institute, 2012). The incidence rate of NHLs was higher for CML patients than for the general population but this is not significant. Conclusions: In our cohort, the incidence rate of secondary neoplasms in CML patients was slightly increased compared to the general population. The most common secondary malignancies in CML patients under treatment were cancers of the skin, prostate, colon, lung and NHL. Since the occurrence of secondary neoplasia increases over time, long-term follow-up of CML patients is warranted. Disclosures: Müller: Novartis, BMS: Consultancy, Honoraria, Research Funding. Hochhaus:Novartis, BMS, MSD, Ariad, Pfizer: Consultancy Other, Honoraria, Research Funding. Hehlmann:Novartis: Research Funding.

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

Blood ◽

10.1182/blood.v128.22.539.539 ◽

2016 ◽

Vol 128 (22) ◽

pp. 539-539

Author(s):

Kelly Kenzik ◽

Amitkumar Mehta ◽

Joshua Richman ◽

Meredith Kilgore ◽

Smita Bhatia

Keyword(s):

Cumulative Incidence ◽

Research Funding ◽

Comparison Group ◽

The Elderly ◽

Morbidity And Mortality ◽

Late Mortality ◽

Increased Risk ◽

Late Morbidity ◽

New Onset

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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The Long-Term Incidence of Hospitalization for Ketoacidosis in Adults with Established T1D—A Prospective Cohort Study

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgz003 ◽

2019 ◽

Vol 105 (1) ◽

pp. 231-241 ◽

Cited By ~ 1

Author(s):

Merlin Thomas ◽

Valma Harjutsalo ◽

Maija Feodoroff ◽

Carol Forsblom ◽

Daniel Gordin ◽

...

Keyword(s):

Diabetic Nephropathy ◽

General Population ◽

Density Lipoprotein ◽

Albumin Excretion Rate ◽

History Of ◽

Stage Renal Disease ◽

End Stage ◽

Incidence Of Hospitalization

Abstract Context The long-term natural history of diabetic ketoacidosis (DKA) and its risk factors are poorly understood. Objective To determine the long-term incidence and predictors of DKA in adults with longstanding type 1 diabetes (T1D). Design All hospitalizations and deaths due to DKA between 1996 and 2016 were identified in 4758 adults with T1D from the Finnish Diabetic Nephropathy Study (FinnDiane), and a cohort of 16 224 adults with T1D from the Finnish general population. Results Between 1996 and 2015, there were 1228 DKA events in the FinnDiane participants (1.4/100 person-years) and 4914 DKA events (1.8/100 person-years) in adults with T1D from the general population. The majority were hospitalized only once. There was a modest increase in the frequency of DKA in the FinnDiane over the follow-up (~2.4%/year [95% CI, 0.3–4.5%]; P = 0.03). Predictors of DKA were glucose control, CSII, smoking and alcohol consumption, and raised high-density lipoprotein cholesterol and triacylglycerides. Diabetic nephropathy and renal impairment were associated with DKA; patients with end-stage renal disease, macroalbuminuria, and microalbuminuria had 2.09-fol (95% CI, 1.40–3.12), 1.65-fold (95% CI, 1.23–2.19), and 0.87-fold (95% CI, 0.61–1.24) risk of DKA compared with patients with normal albumin excretion rate, respectively. Patients with an estimated glomerular filtration rate <60 mL/min/1.73 m2 were also more likely to be hospitalized for DKA (HR 1.71 [95% CI, 1.26–2.67]). Conclusions DKA remains a common cause of hospitalization in individuals with longstanding T1D. These data suggest that the goal to use SGLT2 inhibitors for their vasculo- and renoprotective actions may be problematic, as those most likely to benefit may also have the highest risk for DKA.

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P4147Declining risk of heart failure hospitalisation following first acute myocardial infarction in Scotland between 1990 and 2015

European Heart Journal ◽

10.1093/eurheartj/ehz745.0719 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

K F Docherty ◽

A M Jackson ◽

R T Campbell ◽

R L Godeseth ◽

M C Petrie ◽

...

Keyword(s):

Myocardial Infarction ◽

Heart Failure ◽

Acute Myocardial Infarction ◽

Sensitivity Analysis ◽

Secondary Prevention ◽

Cumulative Incidence ◽

Adjusted Risk ◽

Risk Of Death

Abstract Background Mortality from acute myocardial infarction (AMI) has declined, increasing the pool of survivors at risk of later development of heart failure (HF). However, coronary reperfusion limits infarct size and secondary prevention therapy has improved. In light of these competing influences on risk of HF, we have examined long-term trends in incident HF hospitalisation (HFH) after AMI in a long-term, nationwide study with a single healthcare provider. Purpose To describe temporal trends in the risk of HFH following first AMI occurring in Scotland over a 26 year period. Methods All patients in Scotland discharged alive after a first AMI between 1990 and 2015 were followed until a first HFH or death until the end of 2016 (minimum follow-up 1 year, maximum 27 years). The cumulative incidence of HF was estimated at 1, 5 and 10 years following MI, accounting for the competing risk of death, with adjustment for comorbidities, age, sex and socioeconomic deprivation. In a sensitivity analysis, rates of HFH by AMI type (ST elevation MI [STEMI], non-STEMI and unknown ST type) were calculated for the period 2012 to 2015. Results A total of 184,826 people with no prior history of HF were discharged alive after a first AMI during the period of study. 23,414 (12.7%) had a first HFH during a median follow-up time of 6.8 years. Accounting for the competing risk of death, the cumulative incidence of first HFH, at 1 year, fell between 1990 and 2015 from 5.0% to 2.9%; the 5 year risk fell from 10.4% to 5.8%; 10 year risk from 14.8% to 9.0% (Figure). The adjusted risk of HFH at 1 year after discharge fell by 55% (95% CI 49–60%). The adjusted 5 year risk of HFH fell by 57% (95% CI 53–60%) and 10 year risk fell by 53% (95% CI 50–57%). The adjusted risk of death after first MI fell at 1 year (44%; 95% CI 39–48%), 5 years (37%; 34–39%) and 10 years (34%; 31–36%). The 10 year risk of HF following AMI was higher in older individuals (<55 years vs. ≥85 years HR 3.31; 95% CI 3.08–3.55), if there was HF complicating the index admission (HR 2.14; 95% CI 2.07–2.22), in patients with diabetes (HR 1.77; 95% CI 1.70–1.84), renal disease (HR 1.40; 95% CI 1.32–1.49), atrial fibrillation (HR 1.37; 95% CI 1.31–1.43), and in those not undergoing coronary revascularisation within 30 days of AMI (HR 1.36; 95% CI 1.29–1.43). Similar results were seen at 1 and 5 years. In the sensitivity analysis 2012–2015, the overall rate of HF following STEMI, non-STEMI, and unknown MI type was similar (4.0%, 6.5% and 6.7% respectively). Figure 1 Conclusion Despite an increasing pool of survivors of AMI at risk of HF, the incidence of HF hospitalisation following AMI in Scotland has consistently decreased since 1990. This is despite changes in the treatment and definition of AMI. These trends suggest that better treatment of MI and secondary prevention are having an impact on the risk of HF at a population level. Acknowledgement/Funding This study was funded by an NHS Greater Glasgow and Clyde endowment fund award (GN17CA406)

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Laparoscopic Incisional and Ventral Hernia Repair with Absorbable Tacks in a Long Term Follow-up: A Retrospective Control Study

Reviews on Recent Clinical Trials ◽

10.2174/1574887114666190201111332 ◽

2019 ◽

Vol 14 (2) ◽

pp. 141-146

Author(s):

Simone Zanella ◽

Enrico Lauro ◽

Francesco Franceschi ◽

Francesco Buccelletti ◽

Annalisa Potenza ◽

...

Keyword(s):

Hernia Repair ◽

Ventral Hernia ◽

Ventral Hernia Repair ◽

The Elderly ◽

Long Term Follow Up ◽

Group A ◽

Group B ◽

Absorbable Tacks

Background: Laparoscopic Incisional and Ventral Hernia Repair (LIVHR) is a safe and worldwide accepted procedure performed using absorbable tacks. The aim of the study was to evaluate recurrence rate in a long term follow-up and whether the results of laparoscopic IVH repair in the elderly (≥65 years old) are different with respect to results obtained in younger patients. Methods: One hundred and twenty-nine consecutive patients (74 women and 55 men, median age 67 years, range = 30-87 years) with ventral (N = 42, 32.5%) or post incisional (N = 87, 67.5%) hernia were enrolled in the study. Patients were divided into two groups according to their age: group A (N = 55, 42.6%) aged <65 years and group B (N = 74, 57.4%) aged ≥65 years. Results: The mean operative time was not significantly different between groups (66.7 ± 37 vs. 74 ± 48.4 min, p = 0.4). To the end of 2016, seven recurrences had occurred (group A = 3, group B = 4, p = 1). Complications occurred in 8 (16%) patients in group A and 21 (28.3%) patients in group B. Conclusion: In conclusion, our results confirm that the use of absorbable tacks does not increase recurrence frequency and laparoscopic incisional and ventral repair is a safety procedure also in elderly patients.

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10-Year Follow-Up of a Patient with Cerebral Amyloid Angiopathy

Case Reports in Neurology ◽

10.1159/000501199 ◽

2020 ◽

Vol 12 (Suppl. 1) ◽

pp. 202-206

Author(s):

Min Kyoung Kang ◽

Byung-Woo Yoon

Keyword(s):

Cerebral Amyloid Angiopathy ◽

The Elderly ◽

Amyloid Angiopathy ◽

Spontaneous Intracerebral Hemorrhage ◽

Radiological Features ◽

Magnetic Imaging ◽

Long Term Follow Up ◽

Cerebral Amyloid

We report the case of long-term follow-up of brain magnetic imaging of cerebral amyloid angiopathy. Cerebral amyloid angiopathy is often considered a major cause of spontaneous intracerebral hemorrhage in the elderly. This case illustrates the markedly progressive clinical and radiological features of the vasculopathic process in 10 years.

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