title: Testicular morphological changes in children with acute lymphoblastic leukemia following chemotherapy.
abstract: Morphological changes in the testis induced by chemotherapy given according to the Tokyo Children's Cancer Study Group (TCCSG) regimens were studied in children with acute lymphoblastic leukemia (ALL). After informed consent, testicular biopsies were performed 14 times in 12 patients at the end of treatment. The testicular morphology in all cases had sustained a degree of damage. The tubular fertility index (TFI), calculated as the percentage of seminiferous tubules containing identifiable spermatogonia, was from 0 to 42.8% (mean 33.4%) below the normal value. Infiltration of leukemic cells was the most significant factor contributing to the decrease in TFI. There were no differences in the TFI among the TCCSG protocols. Formation of sperm was recognized in six cases, whose ages were 7, 8, 9, 10, 15 and 19 years. In two children, testicular biopsy was performed twice. In the second biopsy, TFI was elevated and sperm formation with the maturation of Leydig cells was observed. A number of other pathological changes were observed: modification of spermatogonia, Sertoli cells and inclusion bodies in spermatogonia, abnormal maturation of Leydig cells, evidence of interstitial fibrosis and thickening of the basement membrane. These results suggest that recent strong chemotherapy for the treatment of ALL might cause severe but not fatal damage to children's testicular tissue. As chemotherapy escalates, more investigation of testicular function will be necessary.
authors.affiliation: Department of Pediatrics, Jikei University School of Medicine, Tokyo, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Kobayashi
authors.forename: M
authors.initials: M
authors.lastname: Urashima
authors.forename: Y
authors.initials: Y
authors.lastname: Hoshi
authors.forename: H
authors.initials: H
authors.lastname: Uchiyama
authors.forename: K
authors.initials: K
authors.lastname: Fujisawa
authors.forename: J
authors.initials: J
authors.lastname: Akatsuka
authors.forename: K
authors.initials: K
authors.lastname: Maekawa
authors.forename: M
authors.initials: M
authors.lastname: Hurusato
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001706:Biopsy; D002648:Child; D002675:Child, Preschool; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D006801:Humans; D006854:Hydrocortisone / Q000008:administration & dosage; D007985:Leydig Cells / Q000473:pathology; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000473:pathology*; D011239:Prednisolone / Q000008:administration & dosage; D012708:Sertoli Cells / Q000473:pathology; D013093:Spermatogonia / Q000473:pathology; D013737:Testis / Q000473:pathology*
chemical_list: D005047:Etoposide; D004317:Doxorubicin; D003520:Cyclophosphamide; D011239:Prednisolone; D006854:Hydrocortisone; D008727:Methotrexate