Late endocrine effects after hematopoietic stem cell transplantation in children with 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.

Long-term endocrine sequelae after hematopoietic stem cell transplantation in children and adolescents

“…However, those study populations differed considerably in their demographic characteristics, underlying diseases, method of HSCT, preconditioning regimens, and presence or severity of GVHD. The overall prevalence of late endocrine effects from HSCT in those studies ranged from 35.7% to 65.2% [ 8 , 9 , 12 ]. Our group previously reported that endocrine complications occurred in 30% of children with noncentral nervous system solid tumors; among them, 63.3% had undergone HSCT [ 21 ].…”

“…Although demographic factors, chemotherapy, radiation, GVHD, and glucocorticoid use all affect the development of endocrine complications, previous studies reported that the age at HSCT significantly influences clinical outcomes and chronic health issues in childhood cancer survivors [ 8 , 9 ]. Several comparative studies have assessed endocrine outcomes in childhood cancer survivors according to age or pubertal stage at HSCT [ 10 - 12 ]. They reported that age at HSCT affects growth and gonadal function.…”

Thyroid function disorders and secondary cancer following haematopoietic stem cell transplantation in pediatrics: State of the art and practical recommendations for a risk-based follow-up

“…The potentially lower occurrence of endocrine late effects following treosulfan versus busulfan has been extensively investigated in the last decade, but with a specific focus on gonadal function ( 57 ). Only recently, two retrospective studies have highlighted that treosulfan seems to show a trend towards a safer toxicity profile on thyroid health, though longer-lasting additional analyses are warranted before this conclusion can be systematically drawn ( 18 , 58 ).…”

The value of using patient‐reported outcomes for health screening during long‐term follow‐up after paediatric stem cell transplantation for nonmalignant diseases

“…7,8 Due to the HSCT procedure, consisting of chemotherapy and immunosuppressants, or due to the underlying disease, potential late effects can arise, such as gonadal dysfunction, renal insufficiency and cognitive problems, which consequently impair health-related quality of life. [9][10][11][12][13][14] Proper screening for these late effects requires a dedicated long-term follow-up programme, which has been implemented at the Leiden University Medical Center (LUMC) in the Netherlands, providing comprehensive care from 2 years after HSCT onwards. 9,10 The programme includes annual monitoring of both physical and mental health (Supporting Information S1: Figure 1), and continues throughout adulthood due to the potential for late effects to occur even many years after paediatric HSCT.…”

“…HSCT has proven to be an intensive, curative treatment option for various severe paediatric diseases, including nonmalignant disorders such as inborn errors of immunity, hemoglobinopathies and bone marrow failure syndromes 7,8 . Due to the HSCT procedure, consisting of chemotherapy and immunosuppressants, or due to the underlying disease, potential late effects can arise, such as gonadal dysfunction, renal insufficiency and cognitive problems, which consequently impair health‐related quality of life 9–14 . Proper screening for these late effects requires a dedicated long‐term follow‐up programme, which has been implemented at the Leiden University Medical Center (LUMC) in the Netherlands, providing comprehensive care from 2 years after HSCT onwards 9,10 .…”