Children with sickle cell disease: growth and gonadal function after hematopoietic stem cell transplantation

Area of Science:

• Pediatric Hematology
• Endocrinology
• Transplantation Medicine

Background:

• Sickle cell disease (SCD) is a genetic blood disorder requiring intensive treatments like bone marrow transplantation (BMT).
• BMT conditioning regimens, including busulfan and cyclophosphamide, can affect long-term health outcomes, particularly reproductive function.
• Assessing the impact of BMT on growth, puberty, and gonadal function in pediatric SCD patients is crucial for comprehensive care.

Purpose of the Study:

• To evaluate the long-term effects of BMT on growth, pubertal development, and gonadal function in children with sickle cell disease.
• To identify factors influencing gonadal recovery and function post-transplant.
• To characterize the specific patterns of endocrine dysfunction in boys and girls following BMT for SCD.

Main Methods:

• A cohort of 30 children with sickle cell disease who underwent BMT was studied.
• Patients received a conditioning regimen of busulfan (14 or 16 mg/kg) and cyclophosphamide (200 mg/kg).
• Growth parameters, pubertal development, and gonadal hormone levels (FSH, LH, testosterone) were monitored post-transplant.

Main Results:

• Overall growth was normal post-BMT.
• Seven out of ten girls experienced severe ovarian failure requiring estrogen replacement; three showed partial recovery with spontaneous puberty and one successful pregnancy.
• All boys achieved spontaneous puberty, but most had small testes and elevated FSH, indicating germinal epithelium damage; Leydig cell insufficiency was also noted.

Conclusions:

• A significant proportion of girls (7/10) undergoing BMT for SCD experience complete gonadal failure.
• Most boys achieve puberty but suffer from impaired germinal function.
• Lower busulfan doses (14 mg/kg) may be associated with better ovarian function recovery in girls.