Growth and Endocrinological Outcomes in Patients Who Underwent or Did Not Undergo Haematopoietic Stem Cell Transplantation in Prepubertal Age

Hematopoietic stem cell transplantation (HSCT) is a key treatment for pediatric oncology patients but may lead to long-term endocrine and growth complications, including thyroid dysfunction, adrenal insufficiency, impaired bone mineral density, growth deficits, and gonadal dysfunction. This observational cohort study aims to describe growth and endocrine outcomes at specific pubertal stages in pediatric oncology patients who underwent prepubertal HSCT, compared to those who did not receive HSCT in the same age period. Primary objectives include assessing attainment of final height relative to target height, evaluating pubertal growth spurt contribution, and quantifying pubertal sex hormone production (testosterone in males, estradiol in females). Secondary objectives include comparing auxological and endocrine parameters between subgroups that did or did not reach target height, and evaluating the impact of prepubertal exposure to gonadotoxic chemotherapy on growth outcomes. Data will be collected retrospectively and prospectively at key developmental time points according to standard clinical follow-up, without study-specific interventions.

Inclusion criteria

Prepubertal HSCT Group - Pediatric Oncology Patients

• HSCT performed for pediatric oncology between January 2005 and December 2020;
• Pubertal development not yet initiated at the time of HSCT (testicular volume < 4 ml bilaterally, uterine volume < 2.5 ml).

Non-HSCT Group - Pediatric Oncology Patients

• Diagnosis of pediatric oncology between January 2005 and December 2020;
• No HSCT performed before the onset of pubertal development (testicular volume < 4 ml bilaterally, uterine volume < 2.5 ml) during the same period.

For Both Groups

• Received prepubertal chemotherapy including at least one of the following agents: cyclophosphamide, ifosfamide, procarbazine, cisplatin, carboplatin, melphalan, thiotepa, busulfan, treosulfan;
• Spontaneous pubertal development with autonomous progression, without the need for exogenous hormone therapy (testosterone or estradiol);
• Endocrinological follow-up to assess growth progression conducted until the end of pubertal development at the Endocrine-Metabolic Diseases Program, UOC Pediatrics, IRCCS AOUBo;
• Obtain Informed consent.

Exclusion criteria

• Delayed puberty (testicular volume < 4 ml at age > 14 years or Tanner stage 2 breast development at age > 13 years) requiring exogenous hormone therapy with testosterone or estradiol;
• For pediatric oncology patients not undergoing prepubertal HSCT, having received HSCT during pubertal development.