The Association between Deaths Due to Infection and Mutations of the BRAF, FBXW7, NRAS and XPO1 genes: A Report from the LRF CLL4 Trial

* These authors contributed equally Introduction Causes of death and, in particular, deaths due to infection have not been widely studied in randomised trials in chronic lymphocytic leukaemia (CLL). With long-term follow-up (median 13 years), we were able to examine the cause of death in 600/777 patients in the LRF CLL4 trial. Blood samples taken at randomization from 499 patients were available, allowing us to examine the relationship between deaths due to infection and a large panel of genes which are commonly mutated in CLL. Several gene mutations have been linked to earlier death in the LRF CLL4 trial, including mutations of TP53, NOTCH1, SF3B1, EGR2 and MAPK-ERK (Gonzalez et al, J Clin Oncol 2011; 29:2223-9; Oscier et al, Blood 2013; 121:468-75; Young et al, Leukemia 2017; 31:1547-54; Blakemore et al, Leukemia 2020; 34:1760-4). In this study we aimed to identify gene mutations which were specifically associated with death due to infection. Methods In LRF CLL4 patients were randomized between 1999-2004 to receive chlorambucil or fludarabine, with or without cyclophosphamide. Follow-up continued until September 2016. Causes of death were assessed centrally by the principal investigator. Results In the LRF CLL4 trial 614 of 777 patients (79%) died before the end of follow-up. The cause of death was known in 600 patients. Deaths tended to be multifactorial, but infection was a cause of death in 258 patients (43%). Fatal infections were pneumonia (67%), and/or sepsis (38%) and/or opportunistic infections such as aspergillus (11%). Patients who died of infection were more likely than those who died of other causes to have received more than one line of treatment and to have died in the winter months (Table 1). Mutations of BRAF, FBXW7, NRAS and XPO1 were significantly associated with death due to infection versus other deaths. However, with multiple hypothesis testing, NRAS was the only genetic mutation to survive a false discovery rate (FDR) q-value = 0.05 (odds ratio: 17, P = 0.0004). No other significant differences were found between patients who died of infection versus those whose death did not have an infectious cause. In particular, the rate of deaths due to infection was not influenced by other demographic or laboratory factors, nor by the randomised treatment, the response to treatment, or the size/experience of the CLL treatment centre. In multivariate analysis the factors most significantly associated with death from infection versus all other deaths were mutations of the BRAF, FBXW7, NRAS and XPO1 genes (Table 1). Of the 499 patients in the trial for whom gene mutation data were available, 73 (15%) carried one or more of the four gene mutations BRAF (6%), FBXW7 (2%), NRAS (2%) and XPO1 (6%) (Table 2). Only six of these 73 remained alive. Death was caused by infection in 46/67 assessable patients (69%) who had a mutation of one or more of these four genes versus only 129/333 patients (39%) without any of these mutations (odds ratio: 3.46 [95% C.I. 1.98-6.07] P<0.0001). In order to test the robustness of our results, the same analysis was repeated in the full trial, comparing the patients who died of infection with all the other trial patients, including those who remained alive. The presence of one or more of the four gene mutations BRAF, FBXW7, NRAS and XPO1 was the most significant predictor of death from infection in univariate analysis in this larger dataset (odds ratio: 3.92 [95% C.I. 2.34-6.59] P<0.0001). Patients who died of infection lost on average 2 years 4 months of life compared with the median overall survival of all the other trial patients (6 years 11 months, log-rank P<0.0001). Conclusion Patients in LRF CLL4 were at some risk of death due to infection, irrespective of their demographic characteristics, disease stage and treatment history. Nevertheless, those who had received more lines of treatment were particularly at risk, as were those who carried a BRAF, FBXW7, NRAS or XPO1 mutation. A meta-analysis of datasets from other trials could be important to assess the validity of the link between these gene mutations and deaths from infections in patients with CLL and possibly other leukaemias and lymphomas. Careful management of infection risk, together with prophylaxis against infection, may be important in patients who carry one or more of these mutations. Disclosures No relevant conflicts of interest to declare.

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Mortality rate and causes of death in women with self-reported musculoskeletal pain: Results from a 17-year follow-up study

Scandinavian Journal of Pain ◽

10.1016/j.sjpain.2012.12.002 ◽

2013 ◽

Vol 4 (2) ◽

pp. 86-92 ◽

Cited By ~ 20

Author(s):

Anne K. Nitter ◽

Karin Ø. Forseth

Keyword(s):

Risk Factors ◽

Chronic Pain ◽

Mortality Rate ◽

Musculoskeletal Pain ◽

Cause Of Death ◽

Causes Of Death ◽

Sleep Problems ◽

Whole Body ◽

Risk Of Death

AabstractIntroductionChronic musculoskeletal pain represents a significant health problem among adults in Norway. The prevalence of chronic pain is reported to be 35-53% in cross sectional studies of both genders. For many years, it has been a common opinion among medical doctors that chronic pain may indeed reduce a person’s quality of life, but not affect life expectancy. However, over the previous two decades, reports about mortality and cause of death in individuals with chronic pain have been published. So far, several studies conclude that there is an increased mortality in patients with chronic pain, but it is not clear what causes this. Increased occurrences of cardio-vascular death or cancer death have been reported in some studies, but not verified in other studies.Aims of the studyThe aims of this study were to estimate the mortality rate in females with different extent of pain, to identify potential risk factors for death and to investigate if the causes of death differ according to prior reported pain.MethodsThis is a prospective population-based study of all women between 20 and 50 years registered in Arendal, Norway, in 1989 (N = 2498 individuals). At follow-up in 2007, 2261 living females were retraced, 89 had died.All subjects received a questionnaire containing questions about chronic pain (pain ≥ 3 months duration in muscles, joints, back or the whole body) as well as 13 sub-questions about pain-modulating factors, non-specific health complaints and sleep problems, by mail in 1990, 1995 and 2007. Only subjects who answered the questionnaire in 1990 were included in the analyses. Of the deceased, 71 had answered the questionnaire in 1990.A multivariate model for cox regression analysis was used in order to clarify if chronic pain, sleep problems, feeling anxious, frightened or nervous and number of unspecific health were risk factors for death.The causes of death of 87 of the deceased individuals were obtained by linking the ID-number with the Norwegian Cause of Death Registry.ResultsThe ratio of deceased responders was 2% (14/870) among those with no pain versus 5% (57/1168) among those with chronic pain at baseline. When separating into chronic regional pain and chronic widespread pain, the mortality rate was respectively 4% and 8% in the different groups. Age adjusted hazard ratio for mortality rate in individuals with initially chronic pain was [HR 2.5 (CI 1.4–4.5)] compared to pain free individuals. In the multivariate analysis, having chronic pain [HR 2.1 (1.1–4.2)] and feeling anxious, frightened or nervous [HR 3.2 (1.8–5.6)] were associated with increased risk of death. There was no difference in death from cardiovascular disease or malignancies between the groups of pain free individuals vs. the group of individuals with chronic pain.ConclusionThe mortality rate was significantly higher for individuals with chronic pain compared to pain free individuals, adjusted for age. In addition, feeling anxious, frightened or nervous were risk factors for death. There was an increase in all-cause mortality.

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The association between deaths from infection and mutations of the BRAF, FBXW7, NRAS and XPO1 genes: a report from the LRF CLL4 trial

Leukemia ◽

10.1038/s41375-021-01165-w ◽

2021 ◽

Author(s):

Monica Else ◽

Stuart J. Blakemore ◽

Jonathan C. Strefford ◽

Daniel Catovsky

Keyword(s):

Cause Of Death ◽

Causes Of Death ◽

Lymphocytic Leukaemia ◽

Gene Mutations ◽

Randomised Trials ◽

Long Term Follow Up ◽

11Q Deletion ◽

Careful Management

AbstractCauses of death, in particular deaths due to infection, have not been widely studied in randomised trials in chronic lymphocytic leukaemia. With long-term follow-up (median 13 years) we examined the cause of death in 600/777 patients in the LRF CLL4 trial. Blood samples, taken at randomisation from 499 patients, were available for identifying gene mutations. Infection was a cause of death in 258 patients (43%). Patients dying of infection were more likely than those who died of other causes to have received ≥2 lines of treatment (194/258 [75%] versus 231/342 [68%], P = 0.04) and to have died in the winter months (149/258 [58%] versus 166/342 [49%], P = 0.03), respectively. In patients with mutation data, the factors significantly associated with death from infection versus all other deaths were 11q deletion (47/162 [29%] versus 40/209 [19%], P = 0.03) and mutations of the BRAF, FBXW7, NRAS and XPO1 genes. Death was caused by an infection in 46/67 assessable patients (69%) who had a mutation of one or more of these four genes versus only 129/333 patients (39%) without any of these mutations (odds ratio: 3.46 [95% CI 1.98–6.07] P < 0.0001). Careful management of infection risk, including prophylaxis against infection, may be important in patients who carry these mutations.

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Analysis of competing risks of causes of death and their variation over different time periods in Hodgkin disease

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.18528 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 18528-18528

Author(s):

P. España ◽

A. Sanchez ◽

P. Espinosa ◽

V. Massip ◽

R. Perez-Maestu ◽

...

Keyword(s):

Cause Of Death ◽

Competing Risks ◽

Hodgkin's Disease ◽

Causes Of Death ◽

Hodgkin’S Disease ◽

The Other ◽

University Hospital ◽

Time Periods

18528 Background: Hodgkin’s disease is put forward as a model of curable illness. However, long-term studies show an excessive mortality in relation to the general population. The only way for detecting these causes are the long-term follow-up clinical studies, even these long-term follow-ups may not be fully representative of current causes of death. Methods: All patients diagnosed with HD at the University Hospital “Clínica Puerta de Hierro” between 1967 and 2003 were included. The competing risks of causes of death and the vital situation were examined in three time periods. Three cohorts were compared: cohort A with patients treated before 1980, B with those treated 1981–1986 and C from 1986 on. Results: We studied 534 patients, with a median follow-up time of 9.1 years for the whole cohort. The 5, 15 and 20-year Kaplan-Meier survival estimates for all patients were 81%, 72% and 65%, respectively. At the close of the study, 337 (63.1%) were alive and 170 (31.8%) had died. In general, the most common cause was the progress of Hodgkin’s disease, followed by deaths due to a second tumor. By time periods, we found statistically significant differences between cohort A and the other two cohorts, with less LD and MC histology, fewer advanced stages and fewer combined treatments in the latter. Between cohorts B and C there were only differences in the histological results, with less LD and MC and increased NS in the latter. Survival was significantly worse in the first period than in the other two (p<0.001) and in the three periods the main cause of death was tumor progression. Conclusions: The progression of Hodgkin’s disease is the main cause of death in all the periods studied. Over time a clear reduction in death related to the toxicity of treatments was seen. In the light of our results, the question is posed as to whether the survival and causes of death series for those patients treated since the 1970s are telling us about a real situation. Patients die now for reasons that are different from in the 1970s and this is important when planning preventive and clinical research activity. No significant financial relationships to disclose.

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Inhibitors and mortality in persons with nonsevere hemophilia A in the United States

Blood Advances ◽

10.1182/bloodadvances.2020002626 ◽

2020 ◽

Vol 4 (19) ◽

pp. 4739-4747

Author(s):

Ming Y. Lim ◽

Dunlei Cheng ◽

Michael Recht ◽

Christine L. Kempton ◽

Nigel S. Key

Keyword(s):

United States ◽

Cause Of Death ◽

Causes Of Death ◽

Hemophilia A ◽

Epidemiological Data ◽

The United States ◽

Early Age ◽

Risk Of Death ◽

Increased Risk

Abstract Although persons with nonsevere hemophilia A (NSHA) account for about one-half of the hemophilia A population, epidemiological data in this subset of individuals are scarce. We set out to describe the clinical characteristics of persons with NSHA with inhibitors, and to determine mortality rates, predictors of mortality, and primary causes of death in persons with NSHA in the United States over a 9-year period (2010-2018). We queried the American Thrombosis and Hemostasis Network dataset (ATHNdataset) for information on demographics, inhibitor status, and date and cause of death. A total of 6624 persons with NSHA (86.0% men; 14.0% women) were observed for an average of 8.5 years; total 56 119 person-years . The prevalence of inhibitors was 2.6% (n = 171), occurring at a median age of 13 years. At the end of follow-up, 136 persons died at a median age of 63 years; an age-adjusted mortality rate of 3.3 deaths per 1000 person-years. Three deaths occurred in inhibitor participants. Presence of inhibitors was not associated with increased mortality risk (hazard ratio [HR], 0.7, 95% confidence interval [CI], 0.2-2.3). Factors independently associated with increased risk of death (HR, 95% CI) were the following: age (10-year increase) (2.1, 2.0-2.4); male (2.6, 1.0-6.4); hepatitis C (2.2, 1.5-3.1); and HIV (3.6, 2.2-6.0). The most common primary cause of death was malignancy (n = 27, 20.0%). In persons with NSHA, the development of inhibitors occurred at an early age and was not associated with increased mortality.

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Causes of Mortality in Older People With Intellectual Disability: Results From the HA-ID Study

American Journal on Intellectual and Developmental Disabilities ◽

10.1352/1944-7558-123.1.61 ◽

2018 ◽

Vol 123 (1) ◽

pp. 61-71 ◽

Cited By ~ 11

Author(s):

Alyt Oppewal ◽

Josje D. Schoufour ◽

Hanne J.K. van der Maarl ◽

Heleen M. Evenhuis ◽

Thessa I.M. Hilgenkamp ◽

...

Keyword(s):

Older Adults ◽

Intellectual Disability ◽

Cause Of Death ◽

Causes Of Death ◽

Circulatory System ◽

Bacterial Diseases ◽

Specific Mortality ◽

Causes Of Mortality ◽

Insight Into

Abstract We aim to provide insight into the cause-specific mortality of older adults with intellectual disability (ID), with and without Down syndrome (DS), and compare this to the general population. Immediate and primary cause of death were collected through medical files of 1,050 older adults with ID, 5 years after the start of the Healthy Ageing and Intellectual Disabilities (HA-ID) study. During the follow-up period, 207 (19.7%) participants died, of whom 54 (26.1%) had DS. Respiratory failure was the most common immediate cause of death (43.4%), followed by dehydration/malnutrition (20.8%), and cardiovascular diseases (9.4%). In adults with DS, the most common cause was respiratory disease (73.3%), infectious and bacterial diseases (4.4%), and diseases of the digestive system (4.4%). Diseases of the respiratory system also formed the largest group of primary causes of death (32.1%; 80.4% was due to pneumonia), followed by neoplasms (17.6%), and diseases of the circulatory system (8.2%). In adults with DS, the main primary cause was also respiratory diseases (51.1%), followed by dementia (22.2%).

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Postmortem examination protocol and systematic re-evaluation reduce the proportion of unexplained stillbirths

Journal of Perinatal Medicine ◽

10.1515/jpm-2019-0426 ◽

2020 ◽

Vol 48 (8) ◽

pp. 771-777

Author(s):

Maria Pekkola ◽

Minna Tikkanen ◽

Mikko Loukovaara ◽

Jouko Lohi ◽

Jorma Paavonen ◽

...

Keyword(s):

Cause Of Death ◽

Medical Records ◽

Retrospective Cohort ◽

Causes Of Death ◽

Postmortem Examination ◽

University Hospital ◽

Obstetrics And Gynecology ◽

Common Cause ◽

Examination Protocol

AbstractBackgroundStillbirth often remains unexplained, mostly due to a lack of any postmortem examination or one that is incomplete and misinterpreted.MethodsThis retrospective cohort study was conducted at the Department of Obstetrics and Gynecology, Helsinki University Hospital, Finland, and comprised 214 antepartum singleton stillbirths from 2003 to 2015. Maternal and fetal characteristics and the results of the systematic postmortem examination protocol were collected from medical records. Causes of death were divided into 10 specific categories. Re-evaluation of the postmortem examination results followed.ResultsBased on our systematic protocol, the cause of death was originally defined and reported as such to parents in 133 (62.1%) cases. Re-evaluation of the postmortem examination results revealed the cause of death in an additional 43 (20.1%) cases, with only 23 (10.7%) cases remaining truly unexplained. The most common cause of stillbirth was placental insufficiency in 56 (26.2%) cases. A higher proportion of stillbirths that occurred at ≥39 gestational weeks remained unexplained compared to those that occurred earlier (24.1% vs. 8.6%) (P = 0.02).ConclusionA standardized postmortem examination and a re-evaluation of the results reduced the rate of unexplained stillbirth. Better knowledge of causes of death may have a major impact on the follow-up and outcome of subsequent pregnancies. Also, closer examination and better interpretation of postmortem findings is time-consuming but well worth the effort in order to provide better counseling for the grieving parents.

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P099: Extending the trimodal distribution of death; trauma patients die at increased rates after discharge. Linking trauma registry data to vital statistics and hospital datasets identifies opportunities to save life

CJEM ◽

10.1017/cem.2020.305 ◽

2020 ◽

Vol 22 (S1) ◽

pp. S100-S100

Author(s):

J. French ◽

C. Somayaji ◽

D. Dutton ◽

S. Benjamin ◽

P. Atkinson

Keyword(s):

Mortality Rate ◽

Cause Of Death ◽

Causes Of Death ◽

Trauma Registry ◽

Vital Statistics ◽

Trauma Patients ◽

Age Group ◽

Post Discharge ◽

One Year

Introduction: The New Brunswick Trauma Registry is a database of injury admissions from eight hospitals throughout the province. Data tracks individuals in-hospital. By linking this information with vital statistics, we are able to observe outcomes post-discharge and can model health outcomes for participants. We want to know how outcomes for trauma patients compare with the general population post discharge. Methods: Using data from 2014-15, we followed over 2100 trauma registry observations for one year and tracked mortality rate per 1,000 people by age-group. We also compared the outcomes of this group to all Discharge Abstract Database (DAD) entries in the province (circa. 7500 total). We tracked mortality in-hospital, at six months, and one year after discharge. We truncated age into groups aged 40-64, 65-84, and 85 or older. Results: In-hospital mortality among those in the trauma registry is approximately 20 per 1,000 people for those age 40-64, 50 per 1,000 people for those aged 65-84, and 150 per 1,000 people aged 85 or older. For the oldest age group this is in line with the expected population mortality rate, for the younger two groups these estimates are approximately 2-4 times higher than expected mortality. The mortality at six-month follow-up for both of the younger groups remains higher than expected. At one-year follow-up, the mortality for the 65-84 age group returns to the expected population baseline, but is higher for those age 40-64. Causes of death for those who die in hospital are injury for nearly 50% of observations. After discharge, neoplasms and heart disease are the most common causes of death. Trends from the DAD are similar, with lower mortality overall. Of note, cardiac causes of death account for nearly as many deaths in the 6 months after the injury in the 40 -64 age group as the injury itself. Conclusion: Mortality rates remain high upon discharge for up to a year later for some age groups. Causes of death are not injury-related. Some evidence suggests that the injury could have been related to the eventual cause of death (e.g., dementia), but questions remain about the possibility for trauma-mitigating care increasing the risk of mortality from comorbidities. For example, cardiac death, which is largely preventable, is a significant cause of death in the 40-64 age group after discharge. Including an assessment of Framingham risk factors as part of the patients rehabilitation prescription may reduce mortality.

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Association between the Use of Backpack and Static Foot Posture in Schoolchildren with Static Pronated Foot Posture: A 36-Month Cohort Study

Children ◽

10.3390/children8090800 ◽

2021 ◽

Vol 8 (9) ◽

pp. 800

Author(s):

Pilar Alfageme-García ◽

Julián Fernando Calderón-García ◽

Alfonso Martínez-Nova ◽

Sonia Hidalgo-Ruiz ◽

Belinda Basilio-Fernández ◽

...

Keyword(s):

Body Mass Index ◽

Multivariate Analysis ◽

Cohort Study ◽

Prospective Study ◽

Odds Ratio ◽

Univariate Analysis ◽

Foot Posture ◽

The Mean ◽

The Impact

Background: Schoolchildren often spend a lot of time carrying a backpack with school equipment, which can be very heavy. The impact a backpack may have on the pronated feet of schoolchildren is unknown. Aims: The objective of this study was to evaluate the association of the backpack use on static foot posture in schoolchildren with a pronated foot posture over 36 months of follow-up. Methods: This observational longitudinal prospective study was based on a cohort of consecutive healthy schoolchildren with pronated feet from fifteen different schools in Plasencia (Spain). The following parameters were collected and measured in all children included in the study: sex, age, height, weight, body mass index, metatarsal formula, foot shape, type of shoes, and type of schoolbag (non-backpack and backpack). Static foot posture was determined by the mean of the foot posture index (FPI). The FPI was assessed again after 36 months. Results: A total of 112 participants used a backpack when going to school. Over the 36-month follow-up period, 76 schoolchildren who had a static pronated foot posture evolve a neutral foot posture. Univariate analysis showed that the schoolchildren using backpacks were at a greater risk of not developing neutral foot (odds ratio [OR]: 2.09; 95% CI: 1.08–4.09). The multivariate analysis provided similar results, where the schoolchildren using a backpack (adjusted OR [aOR]: 1.94; 95% CI: 1.02–3.82) had a significantly greater risk of not developing a neutral foot posture. Conclusions: A weak relationship was found between backpack use and schoolchildren aged from five to eleven years with static pronated feet not developing a neutral foot posture over a follow-up period of 36 months.

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Mortality among seafarers: a register-based follow-up study

Occupational Medicine ◽

10.1093/occmed/kqaa002 ◽

2020 ◽

Vol 70 (2) ◽

pp. 119-122 ◽

Cited By ~ 1

Author(s):

H Rinne ◽

M Laaksonen ◽

V Notkola ◽

R Shemeikka

Keyword(s):

Causes Of Death ◽

Sociodemographic Factors ◽

Proportional Hazard ◽

Proportional Hazard Model ◽

Occupational Risk Factors ◽

Risk Of Death ◽

Cox Proportional Hazard ◽

Changing Practices ◽

Healthy Behaviour

Abstract Background Seafarers are exposed to many occupational risk factors. Aims To study whether there are differences in mortality between seafarers and other employees, whether there are variations in seafarers’ mortality between different seafaring occupations and whether these differences can be explained by sociodemographic factors. Methods A register-based study of all seafarers aged 25–64 years, resident in Finland in 2000 with minimum 5 years of cumulative seafaring experience on Finnish vessels and other employees, followed for mortality 2001–13. Analysis methods included age standardized death rates, mortality ratios (SMR) and Cox proportional hazard model. Results During the follow-up period 2001–13, there were 81,035 person years and 382 deaths in the cohort of seafarers. Seafarers had 1.3 times higher risk of death (men SMR 132, 95% confidence intervals [CI] 118–147, women SMR 125, 95% CI 99–157) than other employees. Mortality was especially high in alcohol-related causes (men SMR 172, 95% CI 126–233, women SMR 262, 95% CI 131–525) and causes related to smoking. Controlling for sociodemographic characters strengthened the risk compared to other occupations. Mortality was high among male deck and engine crew and among male and female galley personnel. The mortality differences between different seafaring occupations were partly explained by adjustments of sociodemographic characters. Conclusions Seafarers still have increased mortality among men after adjustment of sociodemographic characters. Results by causes of death suggest that changing practices to enable healthy behaviour are important.

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Long-term outcomes of survivors of autologous hematopoietic-cell transplantation for refractory and relapsed Hodgkin’s Disease

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.6554 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 6554-6554

Author(s):

K. A. Goodman ◽

V. Serrano ◽

E. R. Riedel ◽

S. Gulati ◽

C. H. Moskowitz ◽

...

Keyword(s):

Hematopoietic Cell Transplantation ◽

Univariate Analysis ◽

Conditioning Regimen ◽

Hematopoietic Cell ◽

High Dose ◽

Cell Transplant ◽

Hematopoietic Cell Transplant ◽

Risk Of Death ◽

Increased Risk

6554 Background: With improvements in survival among refractory/relapsed Hodgkin’s Lymphoma (HL) patients after high-dose chemo-radiotherapy and autologous hematopoietic-cell transplant (AHCT), it is important to evaluate risk of late complications in this heavily treated population. Methods: From 1985–1998, 218 refractory/relapsed HL patients were treated on high dose chemo-radiotherapy and AHCT salvage protocols. 153 (70%) surviving ≥2 years after AHCT were analyzed. All received either radiotherapy with initial therapy or total lymphoid irradiation and involved field boost with the conditioning regimen (43%). Information from surviving patients was obtained through a self-administered questionnaire. The NDI was queried to determine vital status and cause of death. Primary endpoint was non-HL mortality, defined as mortality due to cardiac causes, infection or second malignancy (SM). Competing risk methods were used to calculate cause-specific mortality rates and examine its predictors. All events were calculated from 2 years post-AHCT to date of death/last follow-up. Results: Median follow-up time was 11 years. There have been 51 deaths, 32 due to HL and 19 due to other causes. Eleven deaths were due to SM: AML (3), MDS (2), NHL (2), NSCLC (2), gastric and colon cancer. There were 8 non-SM deaths: cardiac toxicity (4), infection, aplastic anemia, suicide, unknown causes (1 each). The 10 and 15-year overall survival (OS) rates are 64% and 57%, respectively. The 10-year cumulative incidence of death from HL and from non-HL causes were 22% and 13.5% ( table ). By univariate analysis, increased risk of death due to SM was associated only with higher age at AHCT (p=0.02). Conclusions: While HL initially accounts for the majority of deaths among patients surviving high-dose therapy, the HL mortality rate plateaus and risk of death from non-HL mortality increases after 5 years. Yet, even at 15-years, SM risk does not exceed that observed in patients treated with standard regimens. [Table: see text] No significant financial relationships to disclose.

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