Hypogonadotrophism fails to prevent severe testicular damage induced by total body irradiation in a patient with beta-thalassaemia major and acute lymphoblastic leukaemia

Abstract

Summary:Radiation and chemotherapeutic drugs for cancer produce prolonged and often irreversible gonadal damage. To determine whether total body irradiation (TBI)-induced gonadal damage can be prevented by suppression of pituitary gonadotrophin levels, we studied a patient with transfusion dependent homozygous betathalassaemia and acute lymphoblastic leukaemia (ALL) who underwent one-antigen mismatched related bone marrow transplantation (BMT). Our data showed that despite having hypogonadotrophic hypogonadism (HH) prior to BMT, the patient developed primary testicular failure following the procedure, indicating that hypogonadotrophism failed to offer protection against TBIinduced testicular damage in this patient. Although this is an interesting case report, no firm conclusions can be drawn from a single patient. Bone Marrow Transplantation (2001) 28, 989-991. Keywords: hypogonadotrophic hypogonadism; acute lymphoblastic leukaemia; thalassaemia; bone marrow transplantation As the number of recipients of high-dose chemoradiotherapy for haematological and other malignancies making a full recovery continues to rise, there is growing concern about the impact of the sterilising effects of such treatment, especially in young adult survivors. 1 The concept of protection of spermatogenic function from cytotoxic damage stems from the original study of Glode et al, 2 who showed gonadal protection in a prepubertal mouse model by administering gonadotrophin-releasing hormone (GnRH)-agonist during and after cyclophosphamide treatment which is presumed to result in a resting testicular state, thereby rendering spermatogonia quiescent and resistant to chemotherapy. There is no human study to determine the effect of GnRHagonist towards preventing gonadal damage following radiotherapy, and only conflicting results 3,4 are available from animal studies. Recently we have shown in a patient with CLL that GnRH administration can protect against fludarabine-induced testicular damage. 5 As there are interspecies differences in the patterns of recovery of spermatogenesis after cytotoxic drugs, 4 animal data cannot be extrapolated to humans. Also the exact dose, timing and frequency of administration of GnRH for induction of medical hypogonadotrophism in the BMT setting is not fully established. Thus, it is impossible to have an ideal model to study the protective effect of GnRH on spermatogenesis in recipients of chemotherapy or radiotherapy. Case reportTo determine whether high-dose chemo-radiotherapy induced testicular failure can be prevented by hypogonadotrophism, we studied a 34-year-old patient with beta-thalassaemia major and ALL, who underwent a one-antigen mismatched related donor bone marrow transplant. The haematological data have been published before. 6 In summary, he received induction chemotherapy according the MRC ALLX protocol (vincristine, prednisolone, asparaginase, etoposide, cytarabine, thioguanine, daunorubicine), and subsequently a one-antigen mismatched related donor bone marrow transplant. Conditioning consist...

Endocrinopathies after Allogeneic and Autologous Transplantation of Hematopoietic Stem Cells

“…There is one case report describing the failure of preventing TBI-induced testicular germinal cell damage by aGnRH administration. Currently, the higher chance to achieve a conceivement after HSCT, especially after allo-HSCT, is through sperm cryopreservation [55]. …”