Distress, Health-Related Quality of Life (HQOL) and Confidence in Survivorship Information (CSI) in Older (≥60 Years) Hematopoietic Cell Transplant (HCT) Patients

Abstract Background: The use of HCT to treat older (≥60 years) patients with hematological malignancies has markedly increased in recent years, however, the long-term effects of HCT on distress, psychosocial functioning, and HQOL in older HCT survivors is largely unknown. Though older HCT survivors have a higher risk of disease recurrence, they may have less access to resources and subsequently experience more pronounced late effects of disease and treatment. Confidence in Survivorship Information (CSI) in this specific age group has not been reported. Methods: We conducted a secondary analysis on a subgroup of patients enrolled in INSPIRE (NCT01602211) and PCORI-SCP (NCT02200133) clinical trials. Eligibility criteria for inclusion include HCT patients who were ≥ 60 years at time of transplant performed in 2003-2014, survived ≥ 1 year post-transplant with no evidence of disease relapse or secondary cancers. Patients were eligible for inclusion irrespective of transplant type (autologous or allogeneic), diagnosis, donor source or conditioning regimen. Primary endpoint was distress level in older HCT survivors; secondary endpoints included CSI and HQOL outcomes. We collected baseline distress level as measured by Cancer and Treatment Distress (CTXD) score, HQOL (measured by SF-12 Mental and Physical Component Summaries (PCS/MCS) and CSI (measured by a 15-item CSI questionnaire). Sociodemographic, disease and transplant factors were extracted from medical databases. Nonparametric (Wilcoxon rank sum/Kruskal-Wallis) test was conducted for comparing 2 or 3 groups. Spearman correlation and univariate linear regression model were used to evaluate associations between CTXD/CSI and PCS/MCS. Bonferroni correlation was used to adjust for multiple pairwise comparisons within age group. Results: A total of 567 patients satisfied the eligibility criteria and were included in this analysis. Median age at time of HCT was 69 years with 57% male; two-thirds were autologous HCT recipients. Table 1 details patient characteristics. The median CTXD score for older HCT survivors was 0.7 (range 0-2.7, SD 0.6) indicating low/insignificant level of distress post-HCT. 20-30% of HCT survivors reported moderate distress when asked about concerns regarding relapse risk, loss of energy and functional decline. Type of transplant (auto vs allo), age group (<65 years, 65-70 years, ≥70 years), and time from HCT (≤2 years vs > 2 years) showed no apparent effect on reported distress level. CSI median score was 1.4 (range 0-2) which remains consistent with the score reported previously by the original trial including all age groups, indicating that older HCT survivors may have similar level of confidence in their survivorship information as their younger counterparts. Of note, close to 20% of the older HCT survivors reported poor CSI when asked about strategies for prevention and treatment of long-term effects of HCT and when asked about their confidence in availability of community resources to deal with long-term HCT complications. No statistically significant correlation was identified between CSI in older survivors and transplant type, time from HCT, or age group. HQOL outcomes indicated a median PCS of 48.2 (range 21.1 - 62.9) and a median MCS of 54.7 (range of 14.9 - 67.2). Interestingly, even though not reflected on the overall median CTXD and CSI scores for this cohort, a significant individual association between CTXD/CSI and PCS/MCS measures of HQOL was found (Figure 1). A subgroup analysis conducted on older alloHCT recipients confirmed the same findings of clinically insignificant distress level (mean CTXD ≤1.1) while having a similar level of CSI when compared to all age groups. Interestingly, time from HCT (≤2 years vs > 2 years) showed no significant effect on distress level reported by older alloHCT survivors, and cGVHD status did not correlate with CTXD or CSI scores nor with PCS/MCS in older alloHCT survivors. Conclusion: This is the largest study to date to investigate patient-reported distress, CSI and HQOL in older HCT survivors. Our data indicate that older HCT survivors have low levels of stress after HCT and had confidence in survivorship information in most aspects of their care. However, targeted interventions should focus on improving strategies for prevention, treatment and availability of community resources to deal with late effects of HCT; aspects reported as points of low CSI by older HCT survivors. Figure 1 Figure 1. Disclosures Farhadfar: Incyte: Consultancy. Shaw: Orca bio: Consultancy; mallinkrodt: Other: payments. Devine: Be the Match: Current Employment; Orca Bio: Consultancy, Research Funding; Johnsonand Johnson: Consultancy, Research Funding; Sanofi: Consultancy, Research Funding; Magenta Therapeutics: Current Employment, Research Funding; Tmunity: Current Employment, Research Funding; Vor Bio: Research Funding; Kiadis: Consultancy, Research Funding. Majhail: Anthem, Inc: Consultancy; Incyte Corporation: Consultancy. Wingard: Merck: Consultancy; AlloVir: Consultancy; Celgene: Consultancy; Shire: Consultancy; Janssen: Consultancy; Cidara Therapeutics: Consultancy.

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Empowerment among adult patients with type 2 diabetes: age differentials in relation to person-centred primary care, community resources, social support and other life-contextual circumstances

BMC Public Health ◽

10.1186/s12889-021-10855-0 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Nina Simonsen ◽

Anne M. Koponen ◽

Sakari Suominen

Keyword(s):

Social Support ◽

Community Health ◽

Age Groups ◽

Community Support ◽

Community Resources ◽

Age Group ◽

Health Issues ◽

Younger Adults

Abstract Background Rising prevalence of type 2 diabetes (T2D), also among younger adults, constitutes a growing public health challenge. According to the person-centred Chronic Care Model, proactive care and self-management support in combination with community resources enhance quality of healthcare and health outcomes for patients with T2D. However, research is scarce concerning the importance of person-centred care and community resources for such outcomes as empowerment, and the relative impact of various patient support sources for empowerment is not known. Moreover, little is known about the association of age with these variables in this patient-group. This study, carried out among patients with T2D, examined in three age-groups (27–54, 55–64 and 65–75 years) whether person-centred care and diabetes-related social support, including community support and possibilities to influence community health issues, are associated with patient empowerment, when considering possible confounding factors, such as other quality of care indicators and psychosocial wellbeing. We also explored age differentials in empowerment and in the proposed correlates of empowerment. Method Individuals from a register-based sample with T2D participated in a cross-sectional survey (participation 56%, n = 2866). Data were analysed by descriptive statistics and multivariate logistic regression analyses. Results Respondents in the youngest age-group were more likely to have low empowerment scores, less continuity of care, and lower wellbeing than the other age-groups, and to perceive less social support, but a higher level of person-centred care than the oldest group. Community support, including possibilities to influence community health issues, was independently and consistently associated with high empowerment in all three age-groups, as was person-centred care in the two older age-groups. Community support was the social support variable with the strongest association with empowerment across age-groups. Moreover, vitality was positively and diabetes-related distress negatively associated with high empowerment in all age-groups, whereas continuity of care, i.e. having a family/regular nurse, was independently associated in the youngest age-group only. Conclusion Person-centred care and community support, including possibilities to influence community health issues, supports empowerment among adults with T2D. Findings suggest that age is related to most correlates of empowerment, and that younger adults with T2D have specific healthcare needs.

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Treatment Patterns and Outcomes in Elderly Patients with Newly Diagnosed Multiple Myeloma: Results from the Connect® MM Registry

Blood ◽

10.1182/blood-2019-126205 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 3129-3129

Author(s):

Hans C. Lee ◽

Sikander Ailawadhi ◽

Cristina Gasparetto ◽

Sundar Jagannath ◽

Robert M. Rifkin ◽

...

Keyword(s):

Board Of Directors ◽

Research Funding ◽

Causes Of Death ◽

Age Groups ◽

Treatment Patterns ◽

Age Group ◽

Newly Diagnosed ◽

Employment Equity ◽

Advisory Committees ◽

Equity Ownership

Background: Multiple myeloma (MM) is common among the elderly, with 35% of patients (pts) diagnosed being aged ≥75 years (y). With increasing overall life expectancy, the incidence and prevalence of newly diagnosed and previously treated MM patients ≥80 y is expected to increase over time. Because elderly pts are often excluded from clinical trials, data focused on their treatment patterns and clinical outcomes are lacking. The Connect® MM Registry (NCT01081028) is a large, US, multicenter, prospective observational cohort study of pts with newly diagnosed MM (NDMM) designed to examine real-world diagnostic patterns, treatment patterns, clinical outcomes, and health-related quality of life patient-reported outcomes. This analysis reviews treatment patterns and outcomes in elderly pts from the Connect MM Registry. Methods: Pts enrolled in the Connect MM registry at 250 community, academic, and government sites were included in this analysis. Eligible pts were adults aged ≥18 y with symptomatic MM diagnosed ≤2 months before enrollment, as defined by International Myeloma Working Group criteria; no exclusion criteria were applied. For this analysis, pts were categorized into 4 age groups: <65, 65 to 74, 75 to 84, and ≥85 y. Pts were followed from time of enrollment to the earliest of disease progression (or death), loss to follow-up, or data cutoff date of February 7, 2019. Descriptive statistics were used for baseline characteristics and treatment regimens. Survival outcomes were analyzed using Cox regression. Time to progression (TTP) analysis excluded causes of death not related to MM. Results: Of 3011 pts enrolled (median age 67 y), 132 (4%) were aged ≥85 y, and 615 (20%) were aged 75-84 y at baseline. More pts aged ≥85 y had poor prognostic factors such as ISS stage III disease and reduced hemoglobin (<10 g/dL or >2 g/dL <LLN) compared with other age groups, although no notable differences between creatinine and calcium levels were observed across age groups (Table). A lower proportion of elderly pts (75-84 and ≥85 y) received triplet regimens as frontline therapy. More elderly pts received a single novel agent, whereas use of 2 novel agents was more common in younger pts (Table). The most common frontline regimens among elderly pts were bortezomib (V) + dexamethasone (D), followed by lenalidomide (R) + D, whereas those among younger pts included RVD, followed by VD and CyBorD (Table). No pt aged ≥85 y, and 4% of pts aged 75-84 y received high-dose chemotherapy and autologous stem cell transplant (vs 61% in the <65 y and 37% in the 65-74 y age group). The most common maintenance therapy was RD in pts ≥85 y (although the use was low) and R alone in other age groups (Table). In the ≥85 y group, 27%, 10%, and 4% of pts entered 2L, 3L, and 4L treatments respectively, vs 43%, 23%, and 13% in the <65 y group. Progression-free survival was significantly shorter in the ≥85 y age group vs the 75-84 y age group (P=0.003), 65-74 y age group (P<0.001), and <65 y age group (P<0.001; Fig.1). TTP was significantly shorter in the ≥85 y group vs the <65 y group (P=0.020); however, TTP was similar among the 65-74 y, 75-84 y, and ≥85 y cohorts (Fig. 2). Overall survival was significantly shorter in the ≥85 y group vs the 75-84 y, 65-74 y, and <65 y groups (all P<0.001; Fig. 3). The mortality rate was lowest (46%) during first-line treatment (1L) in pts aged ≥85 y (mainly attributed to MM progression) and increased in 2L and 3L (47% and 54%, respectively); a similar trend was observed in the younger age groups. The main cause of death was MM progression (29% in the ≥85 y vs 16% in the <65 y group). Other notable causes of death in the ≥85 y group included cardiac failure (5% vs 2% in <65 y group) and pneumonia (5% vs 1% in <65 y group). Conclusions: In this analysis, elderly pts received similar types of frontline and maintenance regimens as younger pts, although proportions varied with decreased use of triplet regimens with age. Considering similarities in TTP across the 65-74 y, 75-84 y, and ≥85 y cohorts, these real-world data support active treatment and aggressive supportive care of elderly symptomatic pts, including with novel agents. Additionally, further clinical studies specific to elderly patients with MM should be explored. Disclosures Lee: Amgen: Consultancy, Research Funding; GlaxoSmithKline plc: Research Funding; Sanofi: Consultancy; Daiichi Sankyo: Research Funding; Celgene: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Janssen: Consultancy, Research Funding. Ailawadhi:Janssen: Consultancy, Research Funding; Takeda: Consultancy; Pharmacyclics: Research Funding; Amgen: Consultancy, Research Funding; Celgene: Consultancy; Cellectar: Research Funding. Gasparetto:Celgene: Consultancy, Honoraria, Other: Travel, accommodations, or other expenses paid or reimbursed ; Janssen: Consultancy, Honoraria, Other: Travel, accommodations, or other expenses paid or reimbursed ; BMS: Consultancy, Honoraria, Other: Travel, accommodations, or other expenses paid or reimbursed . Jagannath:AbbVie: Consultancy; Merck & Co.: Consultancy; Bristol-Myers Squibb: Consultancy; Karyopharm Therapeutics: Consultancy; Celgene Corporation: Consultancy; Janssen Pharmaceuticals: Consultancy. Rifkin:Celgene: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees. Durie:Amgen, Celgene, Johnson & Johnson, and Takeda: Consultancy. Narang:Celgene: Speakers Bureau. Terebelo:Celgene: Honoraria; Jannsen: Speakers Bureau; Newland Medical Asociates: Employment. Toomey:Celgene: Consultancy. Hardin:Celgene: Membership on an entity's Board of Directors or advisory committees. Wagner:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; American Cancer Society: Other: Section editor, Cancer journal. Omel:Celgene, Takeda, Janssen: Other: Patient Advisory Committees. Srinivasan:Celgene: Employment, Equity Ownership. Liu:TechData: Consultancy. Dhalla:Celgene: Employment. Agarwal:Celgene Corporation: Employment, Equity Ownership. Abonour:BMS: Consultancy; Celgene: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Janssen: Consultancy, Research Funding.

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Predictive Value of Technical Throwing Skills on Nomination Status in Youth and Long-Term Career Attainment in Handball

Sports Medicine - Open ◽

10.1186/s40798-021-00397-5 ◽

2022 ◽

Vol 8 (1) ◽

Author(s):

Till Koopmann ◽

Franziska Lath ◽

Dirk Büsch ◽

Jörg Schorer

Keyword(s):

Logistic Regression ◽

National Level ◽

Age Groups ◽

Age Group ◽

Regression Analyses ◽

Chi Square ◽

Career Attainment ◽

Future Performance ◽

Younger Age

Abstract Background Research on talent in sports aims to identify predictors of future performance. This study retrospectively investigated 1) relationships between young handball field players’ technical throwing skills and (a) their potential nomination to youth national teams and (b) their long-term career attainment 10 years later, and 2) associations between nomination status and career attainment. Results Results from retrospectively predicting nomination status and career attainment using logistic regression analyses show that technical throwing skills were partly able to explain players’ nomination status (Nagelkerke R2: females 9.2%, males 13.1%) and career attainment (Nagelkerke R2: 9.8% for female players). Here, variables throwing velocity and time on exercise showed statistically significant effects. In addition, nomination status and career attainment were shown to be associated using chi-square tests (w of .37 and .23 for female and male players, respectively) and nomination status as a predictor increased the prediction of career attainment remarkably (Nagelkerke R2: females 20.3%, males 12.7%). Conclusions Given these results, basic technical throwing skills may serve rather as a prerequisite in this age group on national level, emphasizing its importance already on lower levels and in younger age groups. Furthermore, advantages from entering the national TID system early especially for females are discussed.

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A milk-borne outbreak of Campylobacter infection

Journal of Hygiene ◽

10.1017/s0022172400026942 ◽

1980 ◽

Vol 84 (3) ◽

pp. 415-419 ◽

Cited By ~ 39

Author(s):

Ian A. Porter ◽

Thomas M. S. Reid

Keyword(s):

Campylobacter Jejuni ◽

Attack Rate ◽

Age Groups ◽

Age Group ◽

Sex Distribution ◽

Unpasteurized Milk ◽

Group Recovery ◽

Campylobacter Infection ◽

Culture Positive

SUMMARYCampylobacter jejuni was isolated from the stools of 148 patients with symptoms and 57 symptomless subjects, and from a milk sock filter, following an outbreak of enteritis associated with consumption of unpasteurized milk. The incubation period rantged from 2–11 days with a peak at 5 days. There were no secondary cases. The attack rate was around 50% Cases occured in all age groups but were maximal in the 1–10 age group. Recovery from symptoms was complete in the majority in less than 1 week. No long term excretors were indentified. There were no differences between culture positive individuals, with or without symptoms, in age or sex distribution or duration of excretion.

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Effect of the COVID-19 lockdown on disease recognition and utilisation of healthcare services in the older population in German: a cross-sectional study

Age and Ageing ◽

10.1093/ageing/afaa260 ◽

2020 ◽

Author(s):

Bernhard Michalowsky ◽

Wolfgang Hoffmann ◽

Jens Bohlken ◽

Karel Kostev

Keyword(s):

Hospital Admissions ◽

Healthcare Services ◽

Routine Care ◽

Cross Sectional Study ◽

Age Group ◽

Sectional Study ◽

Long Term Effects ◽

Older Population ◽

Cross Sectional

Abstract Background There is little evidence about the utilisation of healthcare services and disease recognition in the older population, which was urged to self-isolate during the COVID-19 lockdown. Objectives We aimed to describe the utilisation of physician consultations, specialist referrals, hospital admissions and the recognition of incident diseases in Germany for this age group during the COVID-19 lockdown. Design Cross-sectional observational study. Setting 1,095 general practitioners (GPs) and 960 specialist practices in Germany. Subjects 2.45 million older patients aged 65 or older. Methods The number of documented physician consultations, specialist referrals, hospital admissions and incident diagnoses during the imposed lockdown in 2020 was descriptively analysed and compared to 2019. Results Physician consultations decrease slightly in February (−2%), increase before the imposed lockdown in March (+9%) and decline in April (−18%) and May (−14%) 2020 compared to the same periods in 2019. Volumes of hospital admissions decrease earlier and more intensely than physician consultations (−39 versus −6%, respectively). Overall, 15, 16 and 18% fewer incident diagnoses were documented by GPs, neurologists and diabetologists, respectively, in 2020. Diabetes, dementia, depression, cancer and stroke were diagnosed less frequently during the lockdown (−17 to −26%), meaning that the decrease in the recognition of diseases was greater than the decrease in physician consultations. Conclusion The data suggest that organisational changes were adopted quickly by practice management but also raise concerns about the maintenance of routine care. Prospective studies should evaluate the long-term effects of lockdowns on patient-related outcomes.

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Perceived Exertion in Isometric Muscular Contractions Related to Age, Muscle, Force Level and Duration

Proceedings of the Human Factors Society Annual Meeting ◽

10.1177/154193129203601015 ◽

1992 ◽

Vol 36 (10) ◽

pp. 712-716 ◽

Cited By ~ 2

Author(s):

Joseph M. Deeb ◽

Colin G. Drury

Keyword(s):

Perceived Exertion ◽

Muscle Force ◽

Age Groups ◽

Muscle Group ◽

Isometric Contractions ◽

Age Group ◽

Perceived Effort ◽

Muscle Groups ◽

Different Levels

This research was concerned with studying the development and growth of perceived effort of long-term isometric contractions as a function of muscle group (biceps vs quadriceps), of subjects with different age groups (20–29 vs. 50–59 years old) on long-term muscular isometric contractions (5 minutes) at different levels of %MVC (20, 40, 60, 80 and 100 %MVC). An experiment testing 20 subjects each performing 10 conditions (two muscle groups × five levels of %MVC) showed that the older age group reported Significantly higher perceived exertion at higher levels of %MVC and across time. Furthermore, subjects experienced a higher and faster increase in their perceived exertion when the level of %MVC and time increased.

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Acute paediatric pain management

10.1093/med/9780199642045.003.0073 ◽

2017 ◽

Author(s):

Tom G. Hansen

Keyword(s):

Pain Management ◽

Postoperative Pain ◽

Acute Pain ◽

Regional Anaesthesia ◽

Pain Threshold ◽

Age Groups ◽

Postoperative Pain Management ◽

Psychological Needs ◽

Long Term Effects

Paediatric pain management has made great strides in the past few decades in the understanding of developmental neurobiology, developmental pharmacology, the use of analgesics in children, the use of regional techniques in children, and of the psychological needs of children in pain. The consequences of a painful experience on the young nervous system are so significant that long-term effects can occur, resulting in behavioural changes and a lowered pain threshold for months after a painful event. Accurate assessment of pain in different age groups and the effective treatment of postoperative pain are constantly being refined, with newer drugs being used alone and in combination with other drugs, and continue to be explored. Systemic opioids, paracetamol, non-steroidal anti-inflammatories, and regional anaesthesia alone or combined with additives are currently used to provide effective postoperative analgesia. These modalities are often best utilized when combined as a multimodal approach to treat acute pain in the perioperative setting. The safe and effective management of pain in children includes the prevention, recognition, and assessment of pain; early and individualized treatment; and evaluation of the efficacy of treatment. This chapter discusses selected topics in paediatric acute pain management, with more specific emphasis placed on pharmacology and regional anaesthesia in the treatment of acute postoperative pain management.

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Long-Term Complications of Lymphoma and Its Treatment

Journal of Clinical Oncology ◽

10.1200/jco.2010.32.8427 ◽

2011 ◽

Vol 29 (14) ◽

pp. 1885-1892 ◽

Cited By ~ 57

Author(s):

Andrea K. Ng ◽

Ann LaCasce ◽

Lois B. Travis

Keyword(s):

Late Effects ◽

Hodgkin’S Lymphoma ◽

Early Stage ◽

Large Body ◽

Hodgkin's Lymphoma ◽

Long Term Effects ◽

Early Stage Disease ◽

Long Term Follow Up

As a result of therapeutic advances, there is a growing population of survivors of both Hodgkin's lymphoma (HL) and non-Hodgkin's lymphoma (NHL). A thorough understanding of the late effects of cancer and its treatment, including the risk of developing a second malignancy and non-neoplastic complications, most notably cardiac disease, is essential for the proper long-term follow-up care of these patients. For HL survivors cured in the past 5 decades, a large body of literature describes a range of long-term effects, many of which are related to extent of treatment. These studies form the basis for many of the follow-up recommendations developed for HL survivors. As HL therapy continues to evolve, however, with an emphasis toward treatment reduction, in particular for early-stage disease, it will be important to rigorously observe this new generation of patients long term to document and quantify late effects associated with modern treatments. Although data on late effects after NHL therapy have recently emerged, the formulation of structured follow-up plans for this heterogeneous group of survivors is challenging, given the highly variable natural history, treatments, and overall prognosis. However, the chemotherapy and radiation therapy approaches for some types of NHL are similar to that for HL; thus, some of the follow-up guidelines for patients with HL may also be transferrable to selected survivors of NHL. Additional work focused on treatment-related complications after NHL will facilitate the development of follow-up programs, as well as treatment refinements to minimize late effects in patients with various types of NHL.

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Risks in the built environment

Proceedings of the Royal Society of London Series A - Mathematical and Physical Sciences ◽

10.1098/rspa.1981.0082 ◽

1981 ◽

Vol 376 (1764) ◽

pp. 151-165 ◽

Cited By ~ 3

Keyword(s):

Control Systems ◽

Perceived Risk ◽

Age Groups ◽

Long Term Effects ◽

Accidental Injury ◽

Perceptions Of Risk ◽

Comprehensive Information ◽

And Control ◽

Transport Accidents

There are good statistics for deaths in transport accidents, fires, and from accidents in the home in Great Britain, and considerable (but less comprehensive) information about injuries and material damage. Information about the causes of these events is much more scanty, and little is known about the long-term effects of accidental injury. The available data are reviewed and the nature, magnitude and frequency of various kinds of risks are analysed for different age groups and in relation to environmental and other factors. The contribution of ‘voluntary’ actions (notably alcohol and smoking) is assessed. Finally, the extent to which both actual and perceived risk can be modified by education, engineering (modifying the design of roads, vehicles, aircraft, homes and fittings), and the enforcement of regulations and control systems is evaluated. While costs cannot easily be measured, false perceptions of risk can lead to wasteful investment, and education and information are essential if resources are to be deployed where they will do most good.

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Imatinib Long Term Effects (ILTE) Study: An Independent, International Study in CML Patients.

Blood ◽

10.1182/blood.v112.11.1099.1099 ◽

2008 ◽

Vol 112 (11) ◽

pp. 1099-1099

Author(s):

Carlo Gambacorti-Passerini ◽

Dong-Wook Kim ◽

François-Xavier Mahon ◽

Giuseppe Saglio ◽

Fabrizio Pane ◽

...

Keyword(s):

Adverse Events ◽

International Study ◽

Imatinib Treatment ◽

Long Term Effects ◽

First Line ◽

Eligibility Criteria ◽

Serious Adverse Events ◽

Second Cancers

Abstract Imatinib is an effective first line therapy for chronic myeloid leukemia (CML) and has substantially changed its biological and clinical behavior. Durable complete cytogenetic responses (CCyR) were reported in the majority of patients, with a rather benign side effect profile, despite the ‘off target’ inhibition of several other kinases, including Kit, PDGFR and Lck. Since available information is largely based on industry-sponsored trials and long-term field studies are lacking, the ILTE study was conceived as an industryindependent, academic, multicenter trial supported by the Italian Drug Safety Agency (AIFA). ILTE is an international study on a retrospective cohort and includes 31 centers in Europe, North/South America, Africa and Asia; therefore it is uniquely positioned to present a global picture of imatinib long-term effects. Consecutive patients with Ph+ CML who started imatinib between 01 September 1999 and 31 December 2004 were eligible if they were in Complete Cytogenetic Response (CCyR) after two years of imatinib treatment. Study endpoints were survival, serious adverse events (SAE, including second cancers), toxicities not qualifying as SAE (NSAE) but judged by the referring physician as substantially impacting quality of life, loss of CCyR, and development of PCR negativity. A total of 957 patients were enrolled, 92% of which met eligibility criteria. The median age of eligible patients was 50 (range 15–92) years; 59% of patients were males and the median follow-up was 3.1 years (excluding the first 2 years of treatment). As of Dec. 31 2007, 2564 person years were available for analysis. Eleven deaths were observed (only 3 of them caused by relapsed CML), with a standardized rate of 0.4/100 person years and an observed/expected ratio of 0.48 (95% CI = 0.24–0.85). One-hundred SAE were recorded (rate 3.9/100 person years, most frequent type “heart failure”), with 21% being considered related to imatinib. Second cancers were documented in 28 patients (rate 1.1/100 person years), with an observed/expected ratio of 1.27 (95% CI = 0.84–1.84). Among the 576 NSAE recorded (0.65/patient) the most frequent types were “edema, cramps, skin fragility, diarrhea”; 71% of them were related to imatinib. A total of 12 patients (1.4 %) discontinued imatinib because of toxicities during the period of observation. Thirty-four patients lost CCyR, corresponding to a rate of 1.4/100 person years (1.0 in patients with imatinib as first-line treatment, 1.5 in patients who were treated with imatinib >6 months after diagnosis), with stable or increasing rates over time. Finally, 214 patients (24.5%) developed durable (> 1 year) PCR negativity. In conclusion, the first report from ILTE shows that CML patients on imatinib die unfrequently of CML related causes, do not appear to have substantially higher second cancer rates than the general population, have mortality rates lower than expected in an age/sex matched population and do not show new types of imatinib-related adverse events. They also experience a low but steady rate of loss of CCyR and develop PCR negativity in approximately ¼ of cases. Follow-up and further analysis are ongoing. (Presented on behalf of the ILTE Investigators group)

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