Adverse health events and late mortality after pediatric allogeneic hematopoietic SCT—two decades of longitudinal follow-up

Wilhelmsson, Mari; Vatanen, Anu; Borgström, Birgit; Gustafsson, Britt; Taskinen, Mervi; Saarinen‐Pihkala, Ulla M.; Winiarski, Jacek; Jahnukainen, Kirsi

doi:10.1038/bmt.2015.43

Cited by 42 publications

(31 citation statements)

References 40 publications

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“…In previous studies, either the number of patients included was smaller [45], the follow-up time was shorter [46], the reported prevalence of endocrine disorders was based on the reported use of hormone replacement therapies [47], or on self-report documentation [48]. In one study with a large cohort of HSCT survivors, most of the patients were younger than 18 years old during the evaluation and part of the cohort was examined by hemato-oncologists rather than endocrinologists [49].…”

Section: Discussionmentioning

confidence: 99%

Endocrine and Metabolic Disturbances in Survivors of Hematopoietic Stem Cell Transplantation in Childhood and Adolescence

Shalitin¹,

Pertman

Yackobovitch‐Gavan³

et al. 2018

Horm Res Paediatr

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Background/Aims: The objective was to evaluate endocrine complications in survivors of hematopoietic stem cell transplantation (HSCT) performed during childhood. Methods: Endocrine dysfunction and metabolic syndrome parameters were assessed by chart review of 178 childhood HSCT survivors (median age at evaluation, 15.5 [range: 3.8–29.8] years; median follow-up, 8.5 [range: 2–23.4] years). Results: The following statistically significant associations were identified (p < 0.05 for all): growth hormone deficiency (17.4%) was associated with cranial/craniospinal irradiation, total body irradiation (TBI), allogeneic HSCT, and longer follow-up. Short adult stature (23.3% of patients who had attained adult height) was associated with cranial/craniospinal irradiation and, in females, with younger age at HSCT. Primary gonadal failure was more prevalent in females (52.6 vs. 24.1%), and was associated with TBI in males and with a primary diagnosis of hematological malignancy in females. Hypothyroidism (25.2%) was associated with previous neck/mediastinal irradiation. Metabolic disturbances included obesity (3.9%), type 2 diabetes (2.2%), impaired glucose tolerance (2.8%), and dyslipidemia (18.5%). Dyslipidemia was associated with a primary diagnosis of hematological malignancy, TBI, and a positive family history of dyslipidemia. Endocrine dysfunction was less frequent in patients who had received fludarabine. Conclusions: Patients after HSCT require long-term surveillance for the detection of endocrine and metabolic disorders. Nonmyeloablative conditioning regimens may reduce the incidence of these complications.

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Section: Discussionmentioning

confidence: 99%

Endocrine and Metabolic Disturbances in Survivors of Hematopoietic Stem Cell Transplantation in Childhood and Adolescence

Shalitin¹,

Pertman

Yackobovitch‐Gavan³

et al. 2018

Horm Res Paediatr

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“…The data suggest an interaction with age, with higher risk of SN in younger recipients exposed to TBI compared with older patients. 39,125 However, the role of TBI in SN risk remains unresolved, with six publications providing strong evidence of increased SN risk from TBI exposure, 16,17,32,46,49,60 and eight studies failing to identify an association between TBI and SN. 22,24,33,37,38,41,59,69 …”

Section: Disease- and Transplant-related Risk Factorsmentioning

confidence: 99%

National Institutes of Health Hematopoietic Cell Transplantation Late Effects Initiative: The Subsequent Neoplasms Working Group Report

Morton

Saber

Baker

et al. 2017

Biology of Blood and Marrow Transplantation

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Subsequent neoplasms (SN) following hematopoietic cell transplantation (HCT) cause significant patient morbidity and mortality. Risks for specific SN types vary substantially, with particularly elevated risks for post-transplant lymphoproliferative disorders, myelodysplastic syndrome/acute myeloid leukemia, and squamous cell malignancies. This consensus document provides an overview of the current state of knowledge regarding SN after HCT and recommends priorities and approaches to overcome challenges and gaps in understanding. Numerous factors have been suggested to impact risk, including patient-related (e.g., age), primary disease-related (e.g., disease type, pre-HCT therapies), and HCT-related characteristics (e.g., type and intensity of conditioning regimen, stem cell source, development of graft-versus-host disease). However, gaps in understanding remain for each of these risk factors, particularly for patients receiving HCT in the current era due to substantial advances in clinical transplantation practices. Additionally, the influence of non-transplant-related risk factors (e.g., germline genetic susceptibility, oncogenic viruses, lifestyle factors) is poorly understood. Clarification of the magnitude of SN risks and identification of etiologic factors will require large-scale, long-term, systematic follow-up of HCT survivors with detailed clinical data. Most investigations of the mechanisms of SN pathogenesis after HCT have focused on immune drivers. Expansion of our understanding in this area will require interdisciplinary laboratory collaborations utilizing measures of immune function and availability of archival tissue from SN diagnoses. Consensus-based recommendations for optimal preventative, screening, and therapeutic approaches have been developed for certain SN after HCT, whereas for other SN, general population guidelines are recommended. Further evidence is needed to specifically tailor preventative, screening, and therapeutic guidelines for SN after HCT, particularly for unique patient populations. Accomplishment of this broad research agenda will require increased investment in systematic data collection with engagement from patients, clinicians, and interdisciplinary scientists in order to reduce the burden of SN in the rapidly growing population of HCT survivors.

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“…1-3 Long-term survivors, however, remain at increased risk for treatment-related morbidity, 4-6 including multiple cardiovascular risk factors (CVRF), such as obesity, elevated blood pressure, glucose intolerance, and dyslipidemia. 7-10 Taken together, these factors constitute the so-called metabolic syndrome, a constellation of abnormalities associated with increased all-cause and cardiovascular mortality. 11, 12 …”

Section: Introductionmentioning

confidence: 99%

Cardiovascular Risk Factors in Survivors of Childhood Hematopoietic Cell Transplantation Treated with Total Body Irradiation: A Longitudinal Analysis

Friedman

Hilden

Moskowitz

et al. 2017

Biology of Blood and Marrow Transplantation

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Hematopoietic cell transplantation (HCT) survivors treated with total body irradiation (TBI) are known to be at increased risk for the development of cardiovascular risk factors (CVRF). We sought to characterize the incidence of CVRF in a TBI-exposed survivor cohort and describe prognostic indicators of their development. Retrospective analysis of CVRF in 1-year survivors of leukemia or lymphoma treated with TBI at Memorial Sloan Kettering from April 1987–May 2011. Eligible participants were≤ 21 years of age at TBI and were not on glucocorticoids at the time of entry to Long-Term Follow-Up. Survivors were assessed for obesity (body mass index [BMI]≥ 95th% for ages≤ 20; ≥30 kg/m2 for ages >20 years), elevated blood pressure, dyslipidemia (elevated triglycerides [TG], low high-density lipoprotein [HDL]), and glucose intolerance (fasting glucose ≥100 mg/dl); those with ≥3 risk factors were deemed to have a CVRF cluster, a surrogate for metabolic syndrome. Cox regression models were used to estimate hazard ratios (HRs) evaluating factors associated with each CVRF. In order to compare prevalence of CVRF in HCT survivors and the general population, survivors were compared to age-, sex-, and race-matched controls from the National Health and Nutrition Examination Survey (NHANES). 123 survivors were evaluated (62.6% male). Median age at TBI was 11.8 years (range 1.6–21.9); median followup was 8.0 years (1.01–24.6); median age at last followup 20.1 years (4.0–41.3). Five-year cumulative incidence of elevated blood pressure, elevated glucose, low HDL, hypertriglyceridemia, and obesity was 14.7%, 10.5%, 26.8%, 39.2%, and 16.0%, respectively, while 10-year cumulative incidence was 28.8%, 33.1%, 52.0%, 65.0%, and 18.6%, respectively. The cumulative incidence of CVRF cluster rose from 10.6% (5.6–17.5) at 5 years to 28.4% (18.8–38.7) at 10 years. In multivariate analysis, growth hormone (GH) deficiency (HR 8.6; 95% CI, 2.1–34.4, p=0.002), history of cranial radiation (HR 4.0; 95% CI, 1.7–9.6, p=0.002), and grade II-IV acute GVHD (HR 4.2; 95% CI, 1.5–12.2, p=0.008) were associated with risk of developing CVRF cluster. HCT survivors had an increased prevalence of hypertriglyceridemia and low HDL, but not glucose intolerance, elevated blood pressure, or CVRF cluster, when compared to a random sample of matched population controls. Given the young age of this HCT survivor cohort, these data highlight the importance of routine screening for CVRF starting in childhood among those exposed to TBI.

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Adverse health events and late mortality after pediatric allogeneic hematopoietic SCT—two decades of longitudinal follow-up

Cited by 42 publications

References 40 publications

Endocrine and Metabolic Disturbances in Survivors of Hematopoietic Stem Cell Transplantation in Childhood and Adolescence

Endocrine and Metabolic Disturbances in Survivors of Hematopoietic Stem Cell Transplantation in Childhood and Adolescence

National Institutes of Health Hematopoietic Cell Transplantation Late Effects Initiative: The Subsequent Neoplasms Working Group Report

Cardiovascular Risk Factors in Survivors of Childhood Hematopoietic Cell Transplantation Treated with Total Body Irradiation: A Longitudinal Analysis

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