Single Centre Evaluation of Endocrine Complications in Children Treated with Auto- and Allo-Haematopoietic Stem Cell Transplantation (HSCT).
Authors: Wojcik Dorota M. , Niedzielska Ewa , Barg Ewa , Kalwak Krzysztof , Gorczynska Ewa , Doroszko Adrian , Chybicka Alicja 
Published: October 2019

Background The increased number of successfully treated pts with HSCT necessitates continuous observation focused on endocrinological complications.

Significant risk factors for endocrine dysfunctions are age and nutrition state before HSCT, high dose chemotherapy HDC/T, total body irradiation (TBI), prolonged steroid therapy for GvHD and cranial irradiation (CI) given prior to the transplant maneuver.

Objective The aim of this study was to evaluate the occurrence of endocrine complications, in particular disorders of growth and thyroid function, abnormal gonadal function and dysfunction in glucose metabolism in children treated with allo-, and auto-HSCT.

Material and methods The investigated group consisted of :

- 16 patients after auto-HSCT (7 girls, 9 boys) age at transplant maneuver 3–20 years (average 9,56±) transplanted for AML (5), NHL (3), NBL (3), embryonal cancer (2), medulloblastoma, Ewing sarcoma/PNET, HES. High dose chemotherapy (HDC/T) included: BU/MEL (7), BEAM (3). - 30 patients after allo-HSCT (20 girls, 10 boys) age at transplant manoveur 3–17 years (average 9,56±). Indications were ALL (11), AML (5), CML (6), MDS (2), NHL, JMML, SAA, Blackfan-Diamonds anaemia, SCID, RMS. According to donor availability there were MSD (13) patients, MUD (11) and HLA-mismatched related (6). The preparative regimen consisted of HDC/T usually BU/MEL (3); BU/CY/VP (6); BU/CY/ATG (5), VP/ATG/TBI (3).

CI prior to grafting received 19 children: auto-HSCT (6), allo-HSCT (13) and TBI 6 patients.

Prolonged high steroid doses (beyond 28 days) received 18 children: auto-HSCT (4) and allo-HSCT (14) before, and 20 after HSCT.

Endocrine function was evaluated in average after 24 months in auto-setting and after 26 months in allo-setting. TSH, fT3, fT4, IGF-1, IGFBP-3, HbA1c, FSH, LH, PRL, estradiol and testosterone levels, oral glucose tolerance test, GH test, TRH test, LHRH test (LH, FSH) was performed in each patient. The University Research Committee for Bioethics did consent to this investigation protocol.

Results

16 children (11girls and 5 boys) presented with abnormal puberty: 43,75% after auto- and 34,61% after allo-HSCT. Hypothyroidism occurred in 5 patients necessitating thyroid hormone substitution. Hyperthyroidism was not diagnosed. Elevated level of aTPO was noted in one child only. Impaired GH-excretion after stimulation was documented in 14 pts. Growth and maturation stature is still an ongoing observational study in this subgroup. Growth impairment was documented in 8 patients (6 girls, 2 boys) 13 to 70 months after allo- transplantation (average 36 months). Three children from above group received CI. Growth hormone substitution was instituted in 1 girl (ALL, HLA MM REL, CI). (SDS<−2,0). An impaired glucose-curve with increased excretion of insulin was documented in 12 children. Glucose intolerance was found in 7 patients: 4 treated with auto- and 3 with allo-HSCT. No diabetes mellitus occurred so far.

Conclusions

Early endocrinological care of children treated with both auto-, as well as allo-HSCT is necessary due to a significant risk for hormonal disorders. Early diagnosis of impaired endocrine function together with early substitution therapy will significantly improve the quality of life after HSCT.