Endocrine Sequelae in 157 Pediatric Survivors of Hematopoietic Stem Cell Transplantation (HSCT)

María Güemes; Álvaro Martín-Rivada; Marta Bascuas Arribas; Eva María Andrés-Esteban; Blanca Molina Angulo; Jesús Pozo Román; Jesús Argente

doi:10.1210/jendso/bvac183

Endocrine Sequelae in 157 Pediatric Survivors of Hematopoietic Stem Cell Transplantation (HSCT)

J Endocr Soc. 2022 Nov 26;7(2):bvac183. doi: 10.1210/jendso/bvac183. eCollection 2022 Dec 15.

Authors

María Güemes^{1

2}, Álvaro Martín-Rivada^{1

2}, Marta Bascuas Arribas¹, Eva María Andrés-Esteban³, Blanca Molina Angulo⁴, Jesús Pozo Román^{1

2

5

6}, Jesús Argente^{1

2

5

6

7}

Affiliations

¹ Departments of Pediatrics & Pediatric Endocrinology, Hospital Infantil Universitario Niño Jesús, 28009 Madrid, Spain.
² Research Institute "La Princesa," 28009 Madrid, Spain.
³ Department of Statistics, Hospital Infantil Universitario Niño Jesús, 28009 Madrid, Spain.
⁴ Department of Hematoncology and Bone Marrow Transplant, Hospital Infantil Universitario Niño Jesús, 28009 Madrid, Spain.
⁵ Department of Pediatrics, Universidad Autónoma de Madrid, 28029 Madrid, Spain.
⁶ Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutriciόn (CIBEROBN), Instituto de Salud Carlos III, 28029 Madrid, Spain.
⁷ IMDEA, Food Institute, CEIUAM + CSI, 28049 Madrid, Spain.

Abstract

Context: Successful rates of hematopoietic stem cell transplantation (HSCT) face paralleled escalation of late endocrine and metabolic effects.

Objective: This work aimed to characterize these sequelae distinguishing between the underlying pathologies and treatments received.

Methods: A retrospective descriptive study was conducted in 157 children post-HSCT (hematopoietic pathology [N = 106], solid tumors [N = 40], and rare entities [N = 11]) followed at a single endocrine department between 2009 and 2019. Regression analysis was used to ascertain association.

Results: Of all patients, 58.7% presented with at least one endocrine abnormality. Endocrinopathies post HSCT were most frequently developed in lymphoblastic leukemia (60.5% of them), whereas myeloid leukemias had the fewest. A total of 64% of patients presented with primary hypogonadism, 52% short stature, and 20% obesity. Endocrinopathy was associated with older age at HSCT (9.78 years [6.25-12.25] vs 6.78 years [4.06-9.75]) (P < .005), pubertal Tanner stage V (P < .001), chronic graft-vs-host disease (GVHD) (P = .022), and direct gonadal therapy (P = .026). The incidence of endocrinopathies was higher in girls (15% more common; P < .02) and in patients who received radiotherapy (18% higher), steroids (17.4% increase), allogenic HSCT (7% higher), thymoglobulin, or cyclophosphamide. Those on busulfan presented with a 27.5% higher rate of primary hypogonadism (P = .003).

Conclusion: More than half of children surviving HSCT will develop endocrinopathies. Strikingly, obesity has risen to the third most frequent endocrine disruption, mainly due to steroids, and partly adhering to the general population tendency. Lymphoblastic leukemia was the condition with a higher rate of endocrine abnormalities. Female sex, older age at HSCT, pubertal stage, allogenic transplant, radiotherapy, alkylating drugs, and GVHD pose risk factors for endocrine disturbances.

Keywords: endocrinopathies; hematopoietic stem cell transplantation; pediatric.