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

Wilhelmsson, Mari; Vatanen, Anu; Borgström, Birgit; Gustafsson, Britt; Taskinen, Mervi; Saarinen‐Pihkala, Ulla M.; Winiarski, Jacek; Jahnukainen, Kirsi

doi:10.1002/pbc.24970

Cited by 35 publications

(40 citation statements)

References 35 publications

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“…The bootstrap sampling used to provide the optimal threshold (necessarily) allows calculation of confidence intervals for sensitivities and specificities for all potential thresholds, and from these we observe that a diagnostic threshold of 17 IU/L for FSH has a 94% probability of avoiding this misdiagnosis, with 95% confidence interval of 90%–97% (Table 2). Our specificity results are in quantitative agreement with a study that reported mean FSH of 22 IU/L in 21 azoospermic CSS compared to 9 IU/L in 10 controls with 81% specificity at a 10 IU/L cutoff [39] compared to our value of 78%. However our calculated sensitivity at this cutoff is higher: 56% [39] compared to 83%.…”

Section: Discussionsupporting

confidence: 92%

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Follicle Stimulating Hormone is an accurate predictor of azoospermia in childhood cancer survivors

et al. 2017

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The accuracy of Follicle Stimulating Hormone as a predictor of azoospermia in adult survivors of childhood cancer is unclear, with conflicting results in the published literature. A systematic review and post hoc analysis of combined data (n = 367) were performed on all published studies containing extractable data on both serum Follicle Stimulating Hormone concentration and semen concentration in survivors of childhood cancer. PubMed and Medline databases were searched up to March 2017 by two blind investigators. Articles were included if they contained both serum FSH concentration and semen concentration, used World Health Organisation certified methods for semen analysis, and the study participants were all childhood cancer survivors. There was no evidence for either publication bias or heterogeneity for the five studies. For the combined data (n = 367) the optimal Follicle Stimulating Hormone threshold was 10.4 IU/L with specificity 81% (95% CI 76%–86%) and sensitivity 83% (95% CI 76%–89%). The AUC was 0.89 (95%CI 0.86–0.93). A range of threshold FSH values for the diagnosis of azoospermia with their associated sensitivities and specificities were calculated. This study provides strong supporting evidence for the use of serum Follicle Stimulating Hormone as a surrogate biomarker for azoospermia in adult males who have been treated for childhood cancer.

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Section: Discussionsupporting

confidence: 92%

“…Our specificity results are in quantitative agreement with a study that reported mean FSH of 22 IU/L in 21 azoospermic CSS compared to 9 IU/L in 10 controls with 81% specificity at a 10 IU/L cutoff [39] compared to our value of 78%. However our calculated sensitivity at this cutoff is higher: 56% [39] compared to 83%.…”

Section: Discussionsupporting

confidence: 92%

Follicle Stimulating Hormone is an accurate predictor of azoospermia in childhood cancer survivors

et al. 2017

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“…Moreover, BU may preserve a higher chance of spermatogenetic recovery, as reported earlier. 20 After extended follow-up, BU seems to be the less toxic myeloablative alternative to TBI and this is supported by other reports. 3,6,21,22 Health conditions that are known to predispose to other, more disabling or life-threatening events were common among the HSCT survivors.…”

Section: Discussionsupporting

confidence: 76%

Adverse health events and late mortality after pediatric allogeneic hematopoietic SCT—two decades of longitudinal follow-up

Wilhelmsson

Vatanen

Borgström

et al. 2015

Bone Marrow Transplant

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Treatment-related late toxicities after pediatric allogeneic hematopoietic SCT (allo-HSCT) are increasingly important as long-term survival has become an expected outcome for many transplanted children and adolescents. In a retrospective cohort study, we assessed long-term health outcomes in 204 allo-HSCT survivors transplanted in childhood or adolescence (o 20 years) between 1978 through 2000 after a median follow-up time of 12 (range 4-28) years. Data on conditioning regimen, adverse health events (AE) and growth and hormonal substitutions (hormone replacement therapies (HRTs)) were obtained from medical records. AEs were graded retrospectively according to Common Terminology Criteria for Adverse Events v3.0. Late deaths (⩾48 months after allo-HSCT) were evaluated separately. Multivariate analysis demonstrated that chronic GVHD (P o0.000) and longer follow-up time (P o0.05) correlated with AEs, whereas CY-based conditioning was inversely correlated (P o 0.002). TBI and longer follow-up duration predicted more severe AEs (P o 0.001 and P o 0.001, respectively). HRTs were more frequent after TBI. Diabetes type II, dyslipidemia and hypertension were detected in 9, 7 and 7% of the survivors, respectively. Late deaths (n = 22) were most frequently due to pulmonary failure (n = 7), followed by secondary malignancy (n = 5). The occurrence of AEs after pediatric allo-HSCT is high and likely to increase during extended follow-up, particularly in patients who have received TBI.

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“…The action of this alkylating agent on haematopoiesis leads to thrombocytopenic effect and reduction in the number of leucocytes (Gibson et al 2003;Molyneux et al 2011). Although alkylating chemotherapeutic agents have been used routinely for conditioning prior to HSCT, these protocols have been associated with high risk of infertility in the oncological patients (Anserini et al 2002;Green et al 2010;Wilhelmsson et al 2014). Fifty per cent of the patients conditioned with cyclophosphamide plus busulphan, for example, remain azoospermic (Anserini et al 2002).…”

Section: Introductionmentioning

confidence: 99%

Seminiferous epithelium damage after short period of busulphan treatment in adult rats and vitamin B₁₂ efficacy in the recovery of spermatogonial germ cells

Vasiliausha

Beltrame

Santi

et al. 2016

Int J Experimental Path

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Several different strategies have been adopted in attempt to recover from chemotherapy-damaged spermatogenesis that is often seen in oncologic patients. In this study, we have evaluated the impact of short period of exposure to busulphan on the haemogram and seminiferous epithelium of adult rats, focusing on spermatogonial depletion and Sertoli cell (SC) integrity. We then examined whether vitamin B supplementation improves the haematological parameters and spermatogonia number. The animals received 10 mg/kg of busulphan (BuG) or busulfan+vitamin B (Bu/B G) on the first and fourth days of treatment. In H.E.-stained testicular sections, the areas of the seminiferous tubule (ST) and seminiferous epithelium were measured. The number of spermatogonia in H.E-stained and PCNA-immunolabelled testicular sections was quantified. The frequency of tubules with abnormal SC nuclei or TUNEL-positive SC was evaluated. Vimentin immunofluorescence in ST was also evaluated. In BuG and Bu/B G, the animals showed leukopenia and thrombocytopenia, but the body weight reduced only in BuG. The areas of ST and seminiferous epithelium decreased in Bu/B G and BuG. In BuG, the number of H.E.-stained and PCNA-immunolabelled spermatogonia reduced significantly. The frequency of tubules containing abnormal SC nuclei and TUNEL-positive SC increased and the vimentin immunoexpression pattern changed. In Bu/B G, the number of H.E.-stained or PCNA-immunolabelled spermatogonia increased fourfold in comparison with BuG. The structural changes in ST after 6 days of busulphan exposure may be associated with the potential effect of this anti-neoplastic agent on SC. The increased number of spermatogonia in the busulphan-treated animals receiving vitamin B indicates that this vitamin can be an adjuvant therapy to improve the fertility in male cancer patients.

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

Cited by 35 publications

References 35 publications

Follicle Stimulating Hormone is an accurate predictor of azoospermia in childhood cancer survivors

Follicle Stimulating Hormone is an accurate predictor of azoospermia in childhood cancer survivors

Adverse health events and late mortality after pediatric allogeneic hematopoietic SCT—two decades of longitudinal follow-up

Seminiferous epithelium damage after short period of busulphan treatment in adult rats and vitamin B₁₂ efficacy in the recovery of spermatogonial germ cells

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

Cited by 35 publications

References 35 publications

Follicle Stimulating Hormone is an accurate predictor of azoospermia in childhood cancer survivors

Follicle Stimulating Hormone is an accurate predictor of azoospermia in childhood cancer survivors

Adverse health events and late mortality after pediatric allogeneic hematopoietic SCT—two decades of longitudinal follow-up

Seminiferous epithelium damage after short period of busulphan treatment in adult rats and vitamin B12 efficacy in the recovery of spermatogonial germ cells

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Seminiferous epithelium damage after short period of busulphan treatment in adult rats and vitamin B₁₂ efficacy in the recovery of spermatogonial germ cells