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Author Spotlight: Exploring the Lifespan Dynamics of Healthy Human Hematopoiesis
Published on: December 8, 2023
Late endocrine effects after hematopoietic stem cell transplantation in children with nonmalignant diseases
L C de Kloet1, J E Bense2, M Y E C van der Stoep3
1Willem-Alexander Children's Hospital, Department of Pediatrics, Division of Endocrinology, Leiden University Medical Center, Leiden, The Netherlands.
Insights
Pediatric hematopoietic stem cell transplantation (HSCT) for nonmalignant conditions frequently causes endocrine issues, particularly gonadal dysfunction in females. Treosulfan conditioning may be less harmful than busulfan for female gonadal health.
Area of Science:
- Pediatric Endocrinology
- Hematology
- Oncology
Background:
- Hematopoietic stem cell transplantation (HSCT) is increasingly used for pediatric nonmalignant diseases.
- Long-term endocrine complications after HSCT for malignant conditions are known, but data for nonmalignant indications are limited.
- Understanding these complications is crucial for improving long-term outcomes in pediatric HSCT survivors.
Purpose of the Study:
- To evaluate the prevalence and risk factors of long-term endocrine complications after pediatric HSCT for nonmalignant diseases.
- Specifically assess gonadal function, near adult height, and thyroid function in survivors.
- Identify potential differences in complication rates based on conditioning agents and patient characteristics.
Main Methods:
- Retrospective evaluation of 197 pediatric HSCT survivors for nonmalignant diseases (hemoglobinopathies, inborn errors of immunity/metabolism, bone marrow failure disorders).
- Median follow-up of 6.2 years.
- Assessment of gonadal function, near adult height (SDS), and thyroid function, with analysis of conditioning agents (busulfan vs. treosulfan) and pubertal status at HSCT.
Main Results:
- High prevalence of gonadal dysfunction: 55% in postpubertal females (43% persistent) and 39% in postpubertal males (32% persistent).
- Female gonadal dysfunction was more frequent with busulfan-based conditioning (HR 10.6).
- Prepubertal males had significantly lower risk of gonadal dysfunction (HR 0.11).
- Impaired near adult height (>2 SDS below parental height) observed in 21% of males and 8% of females.
- Hypothyroidism occurred in 16% of patients, with 4% requiring thyroxine treatment.
Conclusions:
- Endocrine complications, especially gonadal dysfunction, are common in children undergoing HSCT for nonmalignant conditions.
- Treosulfan appears less gonadotoxic than busulfan in females.
- Long-term endocrine surveillance is essential for pediatric HSCT survivors treated for nonmalignant diseases.
Abstract:
The number of children undergoing hematopoietic stem cell transplantation (HSCT) for nonmalignant diseases has increased in recent years. Endocrine complications are common after HSCT for malignant diseases, while little is known about long-term prevalence and risk factors in children transplanted for nonmalignant diseases. We retrospectively evaluated gonadal function, near adult height and thyroid function in 197 survivors of pediatric HSCT for hemoglobinopathies (n = 66), inborn errors of immunity/metabolism (n = 74) and bone marrow failure disorders (n = 57); median follow-up was 6.2 years (range 3.0-10.5). Gonadal dysfunction occurred in 55% of (post)pubertal females, was still present at last assessment in 43% and was more common after busulfan- than treosulfan-based conditioning (HR 10.6, CI 2.2-52.7; adjusted for HSCT indication). Gonadal dysfunction occurred in 39% of (post)pubertal males, was still present at last assessment in 32% and was less common in those who were prepubertal compared to (post)pubertal at HSCT (HR 0.11; CI 0.05-0.21). Near adult height was more than 2 SDS below mean parental height in 21% of males and 8% of females. Hypothyroidism occurred in 16% of patients; 4% received thyroxin treatment. In conclusion, endocrine complications, especially gonadal dysfunction, are common after pediatric HSCT for nonmalignant conditions. In females, treosulfan seems less gonadotoxic than busulfan. Careful long-term endocrine follow-up is indicated.
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