Disturbances of growth and endocrine function after busulphan-based conditioning for haematopoietic stem cell transplantation during infancy and childhood

Abstract

Summary:It is generally assumed that busulphan/cyclophoshamide (Bu/Cy)-based conditioning regimens for haematopoietic stem cell transplantation (SCT) do not affect growth. We evaluated growth and endocrine function after Bu/Cybased conditioning in 64 children without a history of irradiation. Mean height standard deviation scores remained stable, but unexplained disturbances of growth after SCT were found in 17/48 (35%) of the children without growth-limiting disorders (10/23 in patients treated for haematological malignancies). In 10 patients, growth hormone (GH) secretion status was evaluated, and insufficient GH secretion was diagnosed in four patients. Thyroid function was evaluable in 52 patients. Two developed antibody-mediated thyroid disorders and 10 (19%) compensated primary hypothyroidism. Gonadal function was evaluable in 21 patients and was normal in all seven patients treated with low-dose Bu (8 mg/kg), whereas seven of the 14 children receiving high-dose Bu (16-20 mg/kg) developed gonadal failure; the majority of these patients had not been exposed to gonadotoxic therapy prior to Bu/Cy. Of the 49 evaluable patients, 16 developed subclinical hyperparathyroidism. We conclude that, besides gonadal and thyroid dysfunction, impaired growth and hyperparathyroidism often occur after Bu/Cy conditioning for SCT and that growth impairment may be the result of insufficient GH secretion.

Endocrine dysfunction and parameters of the metabolic syndrome after bone marrow transplantation during childhood and adolescence

“…We also found a significant association between final short stature and allogeneic origin of the transplant, as previously described. 5,15 However, this might be explained by the fact that all our patients with Fanconi anemia underwent allogeneic BMT. …”

“…20,21 However, Bakker et al 15 noted an association of impaired growth with busulfan/cyclophosphamide conditioning. They speculated that the 'toxic' actions of corticosteroids on the epiphyseal growth plate can persist in part even after their administration is ceased.…”

“…5,15,34 The outcome of ovarian function following TBI appears to be determined by the age of the patient at the time of irradiation. Previous data indicate that approximately 50% of prepubertal girls given TBI will enter puberty spontaneously and achieve menarche at a normal age, 35 whereas almost all female patients who are more than 12 years old at the time of TBI have ovarian failure, probably because of the decreased number of primordial follicles.…”

“…Three patients (3.3%) were diagnosed with type II diabetes mellitus and three (3.3%) with IGT at a mean age of 21.576.1 years (range, [15][16][17][18][19][20][21][22][23][24][25][26][27][28]. A BMI-SDS of o2 was noted in all three patients with diabetes and in two of the three patients with IGT.…”

Growth and endocrine function in patients with Hurler syndrome after hematopoietic stem cell transplantation

“…[16][17][18][19][20] HSCT as an intervention, however, compounds the problem of short stature. HSCT has been associated with growth suppression, growth hormone (GH) deficiency, abnormal gonadal and thyroid function, and damage to the epiphyseal growth plate and pituitary gland, [21][22][23][24][25][26][27][28][29] all potential causes of short stature.…”