Adult testicular volume predicts spermatogenetic recovery after allogeneic HSCT in childhood and adolescence

Pediatr Blood Cancer. 2014 Jun;61(6):1094-100. doi: 10.1002/pbc.24970.

Abstract

Background: Testicular dysfunction and infertility are of major concern in long-term survivors after allogeneic hematopoietic stem cell transplantation (HSCT). This study assesses predictive factors for very long-term testicular recovery after allogeneic HSCT in childhood and adolescence.

Procedure: Testicular volume, sperm production and long-term need of testosterone substitution were evaluated among 106 male survivors transplanted at Huddinge and Helsinki University Hospitals from 1978 through 2000, at a mean age of 8 ± 4.6 years (range 1-17). A mean ± SD of 13 ± 4.8 years (range 4-28) had elapsed since their HSCT and the mean age of the participants was 22 ± 6.0 years (range 12-42). An adult testicular volume was recorded in 74 patients at a mean age of 19 ± 3.3 years (range 14-36).

Results: Recipients conditioned with busulfan-based regimens or regimens containing only cyclophosphamide had significantly larger adult testicular volumes (mean volume 18 ml and 16 ml vs. 9 ml, P < 0.00001, respectively) and lower serum levels of FSH (mean 9 IU and 5 IU vs. 19 IU, P < 0.01 and 0.001, respectively) compared to those conditioned with total body irradiation (TBI). Multivariate analysis demonstrated that a non-leukemia diagnosis (P < 0.01) and adult testicular volume ≥ 15 ml (P < 0.03) positively impacted spermatogenetic recovery.

Conclusions: A larger adult testicular volume, normal serum levels of FSH and spermatozoa detected in a majority of seminal fluids after busulfan-based or cyclophosphamide conditionings suggest very long-term recovery of spermatogenesis after chemotherapy-based regimens. A simple measurement of adult testicular volume may help predict spermatogenetic potential among pediatric HSCT survivors.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Allografts
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Busulfan / administration & dosage
  • Busulfan / adverse effects
  • Child
  • Child, Preschool
  • Combined Modality Therapy
  • Cranial Irradiation / adverse effects
  • Cyclophosphamide / administration & dosage
  • Cyclophosphamide / adverse effects
  • Follicle Stimulating Hormone / blood
  • Hematopoietic Stem Cell Transplantation*
  • Hormone Replacement Therapy
  • Humans
  • Infant
  • Infertility, Male / blood
  • Infertility, Male / etiology*
  • Infertility, Male / pathology
  • Infertility, Male / prevention & control
  • Male
  • Myeloablative Agonists / administration & dosage
  • Myeloablative Agonists / adverse effects
  • Neoplasms / complications*
  • Neoplasms / drug therapy
  • Neoplasms / surgery
  • Organ Size
  • Postoperative Complications / blood
  • Postoperative Complications / etiology
  • Postoperative Complications / pathology
  • Puberty
  • Radiation Injuries / blood
  • Radiation Injuries / etiology
  • Radiation Injuries / pathology
  • Semen Analysis
  • Spermatogenesis*
  • Survivors*
  • Testis / drug effects
  • Testis / pathology*
  • Testis / radiation effects
  • Testosterone / therapeutic use
  • Transplantation Conditioning / adverse effects
  • Whole-Body Irradiation / adverse effects

Substances

  • Myeloablative Agonists
  • Testosterone
  • Cyclophosphamide
  • Follicle Stimulating Hormone
  • Busulfan