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Late endocrine effects after hematopoietic stem cell transplantation in children with nonmalignant diseases

Bone Marrow Transplantation volume 57, pages 1564–1572 (2022)Cite this article

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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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Fig. 1: Flow chart showing inclusion and exclusion of patients.
Fig. 2: Gonadal dysfunction by gender.
Fig. 3: Growth outcomes by underlying condition.
Fig. 4: Frequency of multiple complications.

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Data availability

The data that support the findings of this study are available from the corresponding author, [APJdP], upon reasonable request.

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Author notes

  1. S. E. Hannema

    Present address: Department of Pediatric Endocrinology, Amsterdam UMC Location Vrije Universiteit Amsterdam, Amsterdam, The Netherlands

  2. These authors contributed equally: L. C. de Kloet, J. E. Bense.

Authors and Affiliations

  1. Willem-Alexander Children’s Hospital, Department of Pediatrics, Division of Endocrinology, Leiden University Medical Center, Leiden, The Netherlands

    L. C. de Kloet & S. E. Hannema

  2. Willem-Alexander Children’s Hospital, Department of Pediatrics, Division of Pediatric Stem Cell Transplantation Program, Leiden University Medical Center, Leiden, The Netherlands

    J. E. Bense, E. G. J. von Asmuth, A. C. Lankester & A. P. J. de Pagter

  3. Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden, The Netherlands

    M. Y. E. C. van der Stoep

  4. Department of Internal Medicine, Leiden University Medical Center, Leiden, The Netherlands

    M. Louwerens

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Contributions

JEB and LCdK collected data, analyzed results and drafted the manuscript. MYECvdS collected data. EGJvA, JEB and LCdK performed the statistical analyses. JEB, LCdK, ML, EGJvA, ACL, APJdP and SEH interpreted the data. SEH designed the study, analyzed results, drafted the manuscript and supervised the project. All authors critically revised the manuscript, approved the final version to be published and agreed to accountability of the work.

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Correspondence to A. P. J. de Pagter.

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de Kloet, L.C., Bense, J.E., van der Stoep, M.Y.E.C. et al. Late endocrine effects after hematopoietic stem cell transplantation in children with nonmalignant diseases. Bone Marrow Transplant 57, 1564–1572 (2022). https://doi.org/10.1038/s41409-022-01755-x

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