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Effect of Childhood Acute Lymphoblastic Leukemia Therapy on Spermatogonia Populations and Future Fertility

Departments of Physiology (M.N.), of Pathology (M.K.), and of Pediatrics (M.N., P.L., T.S.), University of Turku, FIN-20520 Turku, Finland; Department of Woman and Child Health (K.J.) and Division of Obstetrics and Gynecology (V.K.), Karolinska Institute, SE-14186 Stockholm, Sweden; and Division of Hematology-Oncology and Stem Cell Transplantation (K.J.), Hospital for Children and Adolescents, FIN-00029 Helsinki, Finland

Address all correspondence and requests for reprints to: Mirja Nurmio, Department of Physiology, University of Turku, FIN-20520 Turku, Finland. E-mail: mirja.nurmio{at}utu.fi.

Context: Isolation of spermatogonial stem cells before potentially sterilizing cancer therapy, followed by transplantation of these cells into the testis after such treatment, may be an effective approach to prevent infertility among prepubertal boys suffering from acute lymphoblastic leukemia (ALL). A key clinical consideration in this context is the timing of biopsy, if collection of spermatogonia could be delayed from diagnosis to the later phase of leukemia treatment, better patient selection could be offered.

Objective: The objective of the study was to examine the routine testicular biopsy material collected to detect testicular leukemia to evaluate if treatment for leukemia affects numbers and maturation of the spermatogonia during the prepubertal period.

Design and Participants: The study involved 28 testicular biopsies from 23 prepubertal boys treated for ALL.

Outcome Measure: Samples were stained immunohistochemically to evaluate the expression of the spermatogonial markers MAGE 4A, OCT4, CD9, and AP2, and of the Sertoli cell marker WT-1. To relate these findings to gonadal function after sexual maturation, the surviving patients were evaluated as adults.

Results: Several MAGE 4A-, CD9-, or OCT4-positive spermatogonia were detected in testicular biopsies after standard risk therapy without cyclophosphamide, whereas their numbers were significantly reduced in six patients receiving high-risk ALL therapy involving cyclophosphamide. No significant alteration in spermatogonial numbers was associated with testicular leukemia. All patients not treated with cyclophosphamide recovered normal testicular function, with normal sperm quality and endocrine function.

Conclusion: Treatment for childhood leukemia without high-dose cyclophosphamide seldom depletes the spermatogonial stem cell pool totally.