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Male gonadal function after allogeneic hematopoietic stem cell transplantation in childhood: a cross-sectional, population-based study

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Standard

Male gonadal function after allogeneic hematopoietic stem cell transplantation in childhood : a cross-sectional, population-based study. / Mathiesen, Sidsel; Sørensen, Kaspar; Nielsen, Malene Mejdahl; Suominen, Anu; Ifversen, Marianne; Grell, Kathrine; Lähteenmäki, Päivi; Frederiksen, Hanne; Juul, Anders; Müller, Klaus; Jahnukainen, Kirsi.

I: Biology of Blood and Marrow Transplantation, Bind 26, Nr. 9, 2020, s. 1635-1645.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Harvard

Mathiesen, S, Sørensen, K, Nielsen, MM, Suominen, A, Ifversen, M, Grell, K, Lähteenmäki, P, Frederiksen, H, Juul, A, Müller, K & Jahnukainen, K 2020, 'Male gonadal function after allogeneic hematopoietic stem cell transplantation in childhood: a cross-sectional, population-based study', Biology of Blood and Marrow Transplantation, bind 26, nr. 9, s. 1635-1645. https://doi.org/10.1016/j.bbmt.2020.05.009

APA

Mathiesen, S., Sørensen, K., Nielsen, M. M., Suominen, A., Ifversen, M., Grell, K., ... Jahnukainen, K. (2020). Male gonadal function after allogeneic hematopoietic stem cell transplantation in childhood: a cross-sectional, population-based study. Biology of Blood and Marrow Transplantation, 26(9), 1635-1645. https://doi.org/10.1016/j.bbmt.2020.05.009

Vancouver

Mathiesen S, Sørensen K, Nielsen MM, Suominen A, Ifversen M, Grell K o.a. Male gonadal function after allogeneic hematopoietic stem cell transplantation in childhood: a cross-sectional, population-based study. Biology of Blood and Marrow Transplantation. 2020;26(9):1635-1645. https://doi.org/10.1016/j.bbmt.2020.05.009

Author

Mathiesen, Sidsel ; Sørensen, Kaspar ; Nielsen, Malene Mejdahl ; Suominen, Anu ; Ifversen, Marianne ; Grell, Kathrine ; Lähteenmäki, Päivi ; Frederiksen, Hanne ; Juul, Anders ; Müller, Klaus ; Jahnukainen, Kirsi. / Male gonadal function after allogeneic hematopoietic stem cell transplantation in childhood : a cross-sectional, population-based study. I: Biology of Blood and Marrow Transplantation. 2020 ; Bind 26, Nr. 9. s. 1635-1645.

Bibtex

@article{30273a49efd94b08a0786ffb6093a58f,
title = "Male gonadal function after allogeneic hematopoietic stem cell transplantation in childhood: a cross-sectional, population-based study",
abstract = "Male gonadal dysfunction is a frequent late effect after pediatric hematopoietic stem cell transplantation (HSCT), but detailed insights into patterns of male gonadal function at long-term is limited since studies have been retrospective without semen sample data. We investigated 1) the risk of azoospermia and testosterone deficiency, 2) the diagnostic value of markers of spermatogenesis, and 3) paternity at long-term follow-up after pediatric allogeneic HSCT. All surviving men ≥18 years of age transplanted in Denmark or Finland between 1980-2010 were invited to this cross-sectional study. Examinations included a semen sample, reproductive hormones, testicular volumes and screening for chronic graft-versus-host-disease (GvHD). Cumulative (pre-HSCT plus HSCT) treatment doses were calculated. Of 181 eligible patients, 98 participated median (range) 18 (8-35) years after HSCT. Sperm was found in 30 patients, azoospermia in 42, and azoospermia during testosterone substitution in 24 patients. A higher cumulative testicular irradiation dose was associated with increased risk of azoospermia and testosterone substitution (odds ratio [OR] per +1 Gy 1.27, 95{\%}CI 1.14-1.46); p<0.001 and 1.21, 95{\%}CI 1.11-1.38; p<0.001, respectively). All patients treated with >12 Gy had azoospermia and all but one treated with >16 Gy needed testosterone substitution. In patients treated with chemotherapy only (n=23), a higher cumulative cyclophosphamide equivalent dose was associated with increased the risk of azoospermia (OR per +1 g/m2 1.34, 95{\%}CI 1.01-2.15; p=0.037). Pre-pubertal stage at HSCT was a risk factor for testosterone substitution (OR 15.31, 95{\%}CI 2.39-315; p=0.017), while chronic GvHD was unrelated to gonadal dysfunction. Inhibin B was the best surrogate marker of azoospermia (area under the curve 0.91, 95{\%}CI 0.85-0.98, 90{\%} sensitivity and 83{\%} specificity) compared to follicle-stimulating hormone and testicular volume. Of 24 males who had attempted to conceive, six had fathered children. In conclusion, the risk of male gonadal dysfunction after pediatric HSCT is high and depends primarily on the cumulative testicular irradiation dose and pubertal stage at transplant. Our findings pinpoint the need of fertility preservation before HSCT as well as prolonged follow-up of pediatric HSCT patients into adulthood.",
author = "Sidsel Mathiesen and Kaspar S{\o}rensen and Nielsen, {Malene Mejdahl} and Anu Suominen and Marianne Ifversen and Kathrine Grell and P{\"a}ivi L{\"a}hteenm{\"a}ki and Hanne Frederiksen and Anders Juul and Klaus M{\"u}ller and Kirsi Jahnukainen",
note = "Copyright {\circledC} 2020. Published by Elsevier Inc.",
year = "2020",
doi = "10.1016/j.bbmt.2020.05.009",
language = "English",
volume = "26",
pages = "1635--1645",
journal = "Biology of Blood and Marrow Transplantation",
issn = "1083-8791",
publisher = "Elsevier",
number = "9",

}

RIS

TY - JOUR

T1 - Male gonadal function after allogeneic hematopoietic stem cell transplantation in childhood

T2 - a cross-sectional, population-based study

AU - Mathiesen, Sidsel

AU - Sørensen, Kaspar

AU - Nielsen, Malene Mejdahl

AU - Suominen, Anu

AU - Ifversen, Marianne

AU - Grell, Kathrine

AU - Lähteenmäki, Päivi

AU - Frederiksen, Hanne

AU - Juul, Anders

AU - Müller, Klaus

AU - Jahnukainen, Kirsi

N1 - Copyright © 2020. Published by Elsevier Inc.

PY - 2020

Y1 - 2020

N2 - Male gonadal dysfunction is a frequent late effect after pediatric hematopoietic stem cell transplantation (HSCT), but detailed insights into patterns of male gonadal function at long-term is limited since studies have been retrospective without semen sample data. We investigated 1) the risk of azoospermia and testosterone deficiency, 2) the diagnostic value of markers of spermatogenesis, and 3) paternity at long-term follow-up after pediatric allogeneic HSCT. All surviving men ≥18 years of age transplanted in Denmark or Finland between 1980-2010 were invited to this cross-sectional study. Examinations included a semen sample, reproductive hormones, testicular volumes and screening for chronic graft-versus-host-disease (GvHD). Cumulative (pre-HSCT plus HSCT) treatment doses were calculated. Of 181 eligible patients, 98 participated median (range) 18 (8-35) years after HSCT. Sperm was found in 30 patients, azoospermia in 42, and azoospermia during testosterone substitution in 24 patients. A higher cumulative testicular irradiation dose was associated with increased risk of azoospermia and testosterone substitution (odds ratio [OR] per +1 Gy 1.27, 95%CI 1.14-1.46); p<0.001 and 1.21, 95%CI 1.11-1.38; p<0.001, respectively). All patients treated with >12 Gy had azoospermia and all but one treated with >16 Gy needed testosterone substitution. In patients treated with chemotherapy only (n=23), a higher cumulative cyclophosphamide equivalent dose was associated with increased the risk of azoospermia (OR per +1 g/m2 1.34, 95%CI 1.01-2.15; p=0.037). Pre-pubertal stage at HSCT was a risk factor for testosterone substitution (OR 15.31, 95%CI 2.39-315; p=0.017), while chronic GvHD was unrelated to gonadal dysfunction. Inhibin B was the best surrogate marker of azoospermia (area under the curve 0.91, 95%CI 0.85-0.98, 90% sensitivity and 83% specificity) compared to follicle-stimulating hormone and testicular volume. Of 24 males who had attempted to conceive, six had fathered children. In conclusion, the risk of male gonadal dysfunction after pediatric HSCT is high and depends primarily on the cumulative testicular irradiation dose and pubertal stage at transplant. Our findings pinpoint the need of fertility preservation before HSCT as well as prolonged follow-up of pediatric HSCT patients into adulthood.

AB - Male gonadal dysfunction is a frequent late effect after pediatric hematopoietic stem cell transplantation (HSCT), but detailed insights into patterns of male gonadal function at long-term is limited since studies have been retrospective without semen sample data. We investigated 1) the risk of azoospermia and testosterone deficiency, 2) the diagnostic value of markers of spermatogenesis, and 3) paternity at long-term follow-up after pediatric allogeneic HSCT. All surviving men ≥18 years of age transplanted in Denmark or Finland between 1980-2010 were invited to this cross-sectional study. Examinations included a semen sample, reproductive hormones, testicular volumes and screening for chronic graft-versus-host-disease (GvHD). Cumulative (pre-HSCT plus HSCT) treatment doses were calculated. Of 181 eligible patients, 98 participated median (range) 18 (8-35) years after HSCT. Sperm was found in 30 patients, azoospermia in 42, and azoospermia during testosterone substitution in 24 patients. A higher cumulative testicular irradiation dose was associated with increased risk of azoospermia and testosterone substitution (odds ratio [OR] per +1 Gy 1.27, 95%CI 1.14-1.46); p<0.001 and 1.21, 95%CI 1.11-1.38; p<0.001, respectively). All patients treated with >12 Gy had azoospermia and all but one treated with >16 Gy needed testosterone substitution. In patients treated with chemotherapy only (n=23), a higher cumulative cyclophosphamide equivalent dose was associated with increased the risk of azoospermia (OR per +1 g/m2 1.34, 95%CI 1.01-2.15; p=0.037). Pre-pubertal stage at HSCT was a risk factor for testosterone substitution (OR 15.31, 95%CI 2.39-315; p=0.017), while chronic GvHD was unrelated to gonadal dysfunction. Inhibin B was the best surrogate marker of azoospermia (area under the curve 0.91, 95%CI 0.85-0.98, 90% sensitivity and 83% specificity) compared to follicle-stimulating hormone and testicular volume. Of 24 males who had attempted to conceive, six had fathered children. In conclusion, the risk of male gonadal dysfunction after pediatric HSCT is high and depends primarily on the cumulative testicular irradiation dose and pubertal stage at transplant. Our findings pinpoint the need of fertility preservation before HSCT as well as prolonged follow-up of pediatric HSCT patients into adulthood.

U2 - 10.1016/j.bbmt.2020.05.009

DO - 10.1016/j.bbmt.2020.05.009

M3 - Journal article

C2 - 32447044

VL - 26

SP - 1635

EP - 1645

JO - Biology of Blood and Marrow Transplantation

JF - Biology of Blood and Marrow Transplantation

SN - 1083-8791

IS - 9

ER -

ID: 241879383