Accelerated aging after hematopoietic stem cell transplantation in childhood, early menopause, premature cardiovascular aging and frailty

Anu Vatanen

Research output: ThesisDoctoral ThesisCollection of Articles

Abstract

Long-term ovarian function was retrospectively evaluated after allogeneic hematopoietic stem cell transplantation (HSCT) in childhood and adolescence. Cardiovascular risk factors, arterial morphology and stiffness, left ventricular (LV) mass and function, physical fitness and frailty were investigated in adult and adolescent survivors of high-risk neuroblastoma (HR NBL) after autologous HSCT in childhood. The first study population included a cohort of 92 female long-term survivors who were less than 20 years of age when treated at the Children s Hospital, Helsinki University Hospital, or Karolinska University Hospital, Huddinge, between 1978 and 2000. The follow-up data included signs of spontaneous puberty, age at menarche, the use of hormone replacement therapy, pregnancies, and information about pubertal or postpubertal serum FSH levels. The second study population included the Finnish national cohort of 19 long-term HR NBL survivors treated between 1980 and 2000, and 20 age- and sex-matched controls. Clinical examinations included 24h ambulatory blood pressure (BP), very-high-resolution vascular ultrasound, 3D echocardiography and Tissue Doppler Imaging ultrasounds, body composition, physical performance tests and interview. Older age at HSCT and total body irradiation and busulfan-based conditionings were risk factors for early ovarian aging. Leukemia survivors with previous cranial radiotherapy or transplanted after disease relapse were at high risk of premature ovarian failure. The HR NBL survivors showed increased carotid intima-media thickness, plaque formation and stiffness, increased radial artery intima thickness, and increased cardiovascular risk profile when compared to the controls. They had increased LV mass, decreased systolic and diastolic LV function when compared to the controls. Poor LV function associated with cardiac biomarkers, poor physical performance and increased BP. The survivors showed shorter telomere length and increased frequency of frailty phenotype when compared to the controls. The frailty phenotype associated with cardiovascular health and chronic inflammation. In conclusion, our study shows that the adult survivors after HSCT in young age are at risk of early reproductive and vascular aging and frailty. The survivors of pediatric HSCT require regular follow-up in adulthood and interventions for declining ovarian function, cardiovascular risk factors, high BP, subclinical signs of atherosclerosis and decreased cardiac function. Since lifestyle choices can influence cardiovascular health and frailty status, a healthy non-smoking lifestyle and physical activity should be advocated among all survivors who have received HSCT in childhood.
Original languageEnglish
Place of PublicationHelsinki
Publisher
Print ISBNs978-951-51-2065-6
Electronic ISBNs978-951-51-2066-3
Publication statusPublished - 2016
MoE publication typeG5 Doctoral dissertation (article)

Fields of Science

  • 3122 Cancers
  • 3123 Gynaecology and paediatrics

Cite this

@phdthesis{fa3f46c71bb44f3f874898a26e593e99,
title = "Accelerated aging after hematopoietic stem cell transplantation in childhood, early menopause, premature cardiovascular aging and frailty",
abstract = "Long-term ovarian function was retrospectively evaluated after allogeneic hematopoietic stem cell transplantation (HSCT) in childhood and adolescence. Cardiovascular risk factors, arterial morphology and stiffness, left ventricular (LV) mass and function, physical fitness and frailty were investigated in adult and adolescent survivors of high-risk neuroblastoma (HR NBL) after autologous HSCT in childhood. The first study population included a cohort of 92 female long-term survivors who were less than 20 years of age when treated at the Children s Hospital, Helsinki University Hospital, or Karolinska University Hospital, Huddinge, between 1978 and 2000. The follow-up data included signs of spontaneous puberty, age at menarche, the use of hormone replacement therapy, pregnancies, and information about pubertal or postpubertal serum FSH levels. The second study population included the Finnish national cohort of 19 long-term HR NBL survivors treated between 1980 and 2000, and 20 age- and sex-matched controls. Clinical examinations included 24h ambulatory blood pressure (BP), very-high-resolution vascular ultrasound, 3D echocardiography and Tissue Doppler Imaging ultrasounds, body composition, physical performance tests and interview. Older age at HSCT and total body irradiation and busulfan-based conditionings were risk factors for early ovarian aging. Leukemia survivors with previous cranial radiotherapy or transplanted after disease relapse were at high risk of premature ovarian failure. The HR NBL survivors showed increased carotid intima-media thickness, plaque formation and stiffness, increased radial artery intima thickness, and increased cardiovascular risk profile when compared to the controls. They had increased LV mass, decreased systolic and diastolic LV function when compared to the controls. Poor LV function associated with cardiac biomarkers, poor physical performance and increased BP. The survivors showed shorter telomere length and increased frequency of frailty phenotype when compared to the controls. The frailty phenotype associated with cardiovascular health and chronic inflammation. In conclusion, our study shows that the adult survivors after HSCT in young age are at risk of early reproductive and vascular aging and frailty. The survivors of pediatric HSCT require regular follow-up in adulthood and interventions for declining ovarian function, cardiovascular risk factors, high BP, subclinical signs of atherosclerosis and decreased cardiac function. Since lifestyle choices can influence cardiovascular health and frailty status, a healthy non-smoking lifestyle and physical activity should be advocated among all survivors who have received HSCT in childhood.",
keywords = "Aging, Premature, +etiology, Antineoplastic Agents, +adverse effects, Carotid Intima-Media Thickness, Hematopoietic Stem Cell Transplantation, Hypertrophy, Left Ventricular, Menopause, Premature, Neuroblastoma, +therapy, Physical Fitness, Plaque, Atherosclerotic, Primary Ovarian Insufficiency, +chemically induced, Telomere Shortening, Tunica Intima, +ultrasonography, Vascular Stiffness, Whole-Body Irradiation, 3122 Cancers, 3123 Gynaecology and paediatrics",
author = "Anu Vatanen",
note = "M1 - 88 s. + liitteet Helsingin yliopisto Volume: Proceeding volume:",
year = "2016",
language = "English",
isbn = "978-951-51-2065-6",
publisher = "[A. Vatanen]",
address = "Finland",

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Accelerated aging after hematopoietic stem cell transplantation in childhood, early menopause, premature cardiovascular aging and frailty. / Vatanen, Anu.

Helsinki : [A. Vatanen], 2016. 88 p.

Research output: ThesisDoctoral ThesisCollection of Articles

TY - THES

T1 - Accelerated aging after hematopoietic stem cell transplantation in childhood, early menopause, premature cardiovascular aging and frailty

AU - Vatanen, Anu

N1 - M1 - 88 s. + liitteet Helsingin yliopisto Volume: Proceeding volume:

PY - 2016

Y1 - 2016

N2 - Long-term ovarian function was retrospectively evaluated after allogeneic hematopoietic stem cell transplantation (HSCT) in childhood and adolescence. Cardiovascular risk factors, arterial morphology and stiffness, left ventricular (LV) mass and function, physical fitness and frailty were investigated in adult and adolescent survivors of high-risk neuroblastoma (HR NBL) after autologous HSCT in childhood. The first study population included a cohort of 92 female long-term survivors who were less than 20 years of age when treated at the Children s Hospital, Helsinki University Hospital, or Karolinska University Hospital, Huddinge, between 1978 and 2000. The follow-up data included signs of spontaneous puberty, age at menarche, the use of hormone replacement therapy, pregnancies, and information about pubertal or postpubertal serum FSH levels. The second study population included the Finnish national cohort of 19 long-term HR NBL survivors treated between 1980 and 2000, and 20 age- and sex-matched controls. Clinical examinations included 24h ambulatory blood pressure (BP), very-high-resolution vascular ultrasound, 3D echocardiography and Tissue Doppler Imaging ultrasounds, body composition, physical performance tests and interview. Older age at HSCT and total body irradiation and busulfan-based conditionings were risk factors for early ovarian aging. Leukemia survivors with previous cranial radiotherapy or transplanted after disease relapse were at high risk of premature ovarian failure. The HR NBL survivors showed increased carotid intima-media thickness, plaque formation and stiffness, increased radial artery intima thickness, and increased cardiovascular risk profile when compared to the controls. They had increased LV mass, decreased systolic and diastolic LV function when compared to the controls. Poor LV function associated with cardiac biomarkers, poor physical performance and increased BP. The survivors showed shorter telomere length and increased frequency of frailty phenotype when compared to the controls. The frailty phenotype associated with cardiovascular health and chronic inflammation. In conclusion, our study shows that the adult survivors after HSCT in young age are at risk of early reproductive and vascular aging and frailty. The survivors of pediatric HSCT require regular follow-up in adulthood and interventions for declining ovarian function, cardiovascular risk factors, high BP, subclinical signs of atherosclerosis and decreased cardiac function. Since lifestyle choices can influence cardiovascular health and frailty status, a healthy non-smoking lifestyle and physical activity should be advocated among all survivors who have received HSCT in childhood.

AB - Long-term ovarian function was retrospectively evaluated after allogeneic hematopoietic stem cell transplantation (HSCT) in childhood and adolescence. Cardiovascular risk factors, arterial morphology and stiffness, left ventricular (LV) mass and function, physical fitness and frailty were investigated in adult and adolescent survivors of high-risk neuroblastoma (HR NBL) after autologous HSCT in childhood. The first study population included a cohort of 92 female long-term survivors who were less than 20 years of age when treated at the Children s Hospital, Helsinki University Hospital, or Karolinska University Hospital, Huddinge, between 1978 and 2000. The follow-up data included signs of spontaneous puberty, age at menarche, the use of hormone replacement therapy, pregnancies, and information about pubertal or postpubertal serum FSH levels. The second study population included the Finnish national cohort of 19 long-term HR NBL survivors treated between 1980 and 2000, and 20 age- and sex-matched controls. Clinical examinations included 24h ambulatory blood pressure (BP), very-high-resolution vascular ultrasound, 3D echocardiography and Tissue Doppler Imaging ultrasounds, body composition, physical performance tests and interview. Older age at HSCT and total body irradiation and busulfan-based conditionings were risk factors for early ovarian aging. Leukemia survivors with previous cranial radiotherapy or transplanted after disease relapse were at high risk of premature ovarian failure. The HR NBL survivors showed increased carotid intima-media thickness, plaque formation and stiffness, increased radial artery intima thickness, and increased cardiovascular risk profile when compared to the controls. They had increased LV mass, decreased systolic and diastolic LV function when compared to the controls. Poor LV function associated with cardiac biomarkers, poor physical performance and increased BP. The survivors showed shorter telomere length and increased frequency of frailty phenotype when compared to the controls. The frailty phenotype associated with cardiovascular health and chronic inflammation. In conclusion, our study shows that the adult survivors after HSCT in young age are at risk of early reproductive and vascular aging and frailty. The survivors of pediatric HSCT require regular follow-up in adulthood and interventions for declining ovarian function, cardiovascular risk factors, high BP, subclinical signs of atherosclerosis and decreased cardiac function. Since lifestyle choices can influence cardiovascular health and frailty status, a healthy non-smoking lifestyle and physical activity should be advocated among all survivors who have received HSCT in childhood.

KW - Aging, Premature

KW - +etiology

KW - Antineoplastic Agents

KW - +adverse effects

KW - Carotid Intima-Media Thickness

KW - Hematopoietic Stem Cell Transplantation

KW - Hypertrophy, Left Ventricular

KW - Menopause, Premature

KW - Neuroblastoma

KW - +therapy

KW - Physical Fitness

KW - Plaque, Atherosclerotic

KW - Primary Ovarian Insufficiency

KW - +chemically induced

KW - Telomere Shortening

KW - Tunica Intima

KW - +ultrasonography

KW - Vascular Stiffness

KW - Whole-Body Irradiation

KW - 3122 Cancers

KW - 3123 Gynaecology and paediatrics

M3 - Doctoral Thesis

SN - 978-951-51-2065-6

PB - [A. Vatanen]

CY - Helsinki

ER -