Abstract

Background

Preparative regimen consisting of high dose chemotherapy HDC/T and/or cranial irradiation (CI) in combination with prolonged steroid therapy may cause abnormal gonadal function.

Objective

Evaluate puberty disorders in children occurring after HSCT as single center experience.

Material and methods

The study group consisting of 21 patients (13 girls and 8 boys) age 10–20 years at grafting (median 14 years) was prospectively evaluated post grafting. The indications for HSCT were: ALL (5), AML (4), CML (5), MDS (2) and NHL, JMML, SAA, Blackfan Diamond anemia, RMS. According to donor availability 11 children had mached sib donors (MSD), 7 matched unrelated donors (MUD) and 3 patients HLA-mismatched related donors. The preparative regimens consisted of HDC/T usually BU/MEL (2pts); BU/CY/VP (5pts); BU/CY/ATG (4pts) and total body irradiation (TBI) received 3 patients with 12 Gy. CI prior to grafting was delivered to 5 children: 18 Gy (4) and 24 Gy (1). Prolonged high doses steroids (beyond day +28) received 7 children prior to- and 10 children after grafting. Endocrine function after allo-HSCT was evaluated from 10 to 42 (median 26 months). Analysis of LH, FSH, PRL, oestradiol and testosterone levels, fT3, fT4, aTPO, TRH test and LHRH test was performed in all study patients. Bone age according to Pyle-Grulich method was estimated.

Results:

  1. Abnormal gonadal function was present in 12/21 children (9 girls, 3 boys) in average 28 months after HSCT

  2. Primary amenorrhea occurred in 3, secondary amenorrhea in 6 girls.

  3. Delayed bone age was documented in 2 children in average 30 mths post grafting.

  4. No significant correlation was found between children’s age during allo-HSCT and occurrence of puberty disorders.

  5. Gender of children had no effect on evalated variables.

  6. Time elapsing from HSCT did not influence the occurrence of abnormal gonadal function.

  7. No association was found between abnormal gonadal function and TBI, prolonged high doses steroids prior to- and after HSCT.

  8. Occurrence of puberty disorders was statistically significantly blunted by conditioning regimen containing Cyclophosphamide (p=0,019) and Busulfan (p=0,0179) while Melfalan did not turn out such a risk factor.

  9. PRL levels and thyroid function do not have any determination on occurrence of abnormal gonadal function after HSCT.

Conclusion:

  1. Abnormal gonadal function as late effect frequently occure after HSCT.

  2. High-dose Cyclophoshamide and Busulphan tretaed children often had blunted puberty. Melfalan and TBI, however, did not cause such an effect reported by others.

  3. Endocrinological care for patients after HSCT is necessary in order to:

    • - Discover the impaired endocrine function

    • - Initiate correct hormonal substitution therapy

    • - Significantly improve the quality of life after allo- HSCT and

    • - Secondary prevent treatment related complications.

Disclosure: No relevant conflicts of interest to declare.

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