Gonadal Function after Busulfan Compared with Treosulfan in Children and Adolescents Undergoing Allogeneic Hematopoietic Stem Cell Transplant

M. Faraci, T. Diesch, M. Labopin, A. Dalissier, A. Lankester, A. Gennery, M. Sundin, D. Uckan-Cetinkaya, M. Bierings, A.M.J. Peters, M. Garwer, A. Schulz, G. Michel, G. Giorgiani, B. Gruhn, F. Locatelli, S. Giardino, A. Uyttebroeck, F. Rialland, M. Itäla-RemesP. Dreger, P.J. Shaw, V. Bordon, P.G. Schlegel, K. Mellgren, J.M. Moraleda, K. Patrick, P. Schneider, C. Jubert, A. Lawitschka, N. Salooja, G.W. Basak, S. Corbacioglu, R. Duarte, P. Bader, Pediatric and Transplant Complications Working Parties of the European Society for Blood and Marrow Transplantation

Research output: Contribution to journalArticle

Abstract

Gonadal impairment is an important late effect with a significant impact on quality of life of transplanted patients. The aim of this study was to compare gonadal function after busulfan (Bu) or treosulfan (Treo) conditioning regimens in pre- and postpubertal children. This retrospective, multicenter study included children transplanted in pediatric European Society for Blood and Marrow Transplantation (EBMT) centers between 1992 and 2012 who did not receive gonadotoxic chemoradiotherapy before the transplant. We evaluated 137 patients transplanted in 25 pediatric EBMT centers. Median age at transplant was 11.04 years (range, 5 to 18); 89 patients were boys and 48 girls. Eighty-nine patients were prepubertal at transplant and 48 postpubertal. One hundred eighteen children received Bu and 19 Treo. A higher proportion of girls treated with Treo in the prepubertal stage reached spontaneous puberty compared with those treated with Bu (P = .02). Spontaneous menarche was more frequent after Treo than after Bu (P <.001). Postpubertal boys and girls treated with Treo had significantly lower luteinizing hormone levels (P = .03 and P = .04, respectively) compared with the Bu group. Frequency of gonadal damage associated with Treo was significantly lower than that observed after Bu. These results need to be confirmed in a larger population. © 2019
Original languageEnglish
Pages (from-to)1786-1791
Number of pages6
JournalBiology of Blood and Marrow Transplantation
Volume25
Issue number9
DOIs
Publication statusPublished - 2019

Fingerprint

treosulfan
Busulfan
Hematopoietic Stem Cells
Transplants
Transplantation
Bone Marrow
Pediatrics
Menarche
Chemoradiotherapy
Puberty
Luteinizing Hormone
Multicenter Studies
Retrospective Studies
Quality of Life

Keywords

  • Busulfan
  • Gonadal damage
  • Pubertal stage
  • Treosulfan
  • busulfan
  • estradiol
  • follitropin
  • gonadotropin
  • inhibin B
  • luteinizing hormone
  • Muellerian inhibiting factor
  • testosterone
  • treosulfan
  • adolescent
  • adult
  • allogeneic hematopoietic stem cell transplantation
  • Article
  • child
  • chronic myeloid leukemia
  • controlled study
  • female
  • follitropin blood level
  • follow up
  • gonad dysfunction
  • gonad function
  • gonadotropin blood level
  • hemophagocytic syndrome
  • hormone blood level
  • human
  • hypogonadism
  • juvenile myelomonocytic leukemia
  • luteinizing hormone blood level
  • major clinical study
  • male
  • menarche
  • multicenter study
  • pediatric patient
  • prepuberty
  • retrospective study
  • Shwachman syndrome
  • testosterone blood level
  • transplantation conditioning

Cite this

Faraci, M., Diesch, T., Labopin, M., Dalissier, A., Lankester, A., Gennery, A., ... Transplantation, P. A. T. C. W. P. O. T. E. S. F. B. A. M. (2019). Gonadal Function after Busulfan Compared with Treosulfan in Children and Adolescents Undergoing Allogeneic Hematopoietic Stem Cell Transplant. Biology of Blood and Marrow Transplantation, 25(9), 1786-1791. https://doi.org/10.1016/j.bbmt.2019.05.005

Gonadal Function after Busulfan Compared with Treosulfan in Children and Adolescents Undergoing Allogeneic Hematopoietic Stem Cell Transplant. / Faraci, M.; Diesch, T.; Labopin, M.; Dalissier, A.; Lankester, A.; Gennery, A.; Sundin, M.; Uckan-Cetinkaya, D.; Bierings, M.; Peters, A.M.J.; Garwer, M.; Schulz, A.; Michel, G.; Giorgiani, G.; Gruhn, B.; Locatelli, F.; Giardino, S.; Uyttebroeck, A.; Rialland, F.; Itäla-Remes, M.; Dreger, P.; Shaw, P.J.; Bordon, V.; Schlegel, P.G.; Mellgren, K.; Moraleda, J.M.; Patrick, K.; Schneider, P.; Jubert, C.; Lawitschka, A.; Salooja, N.; Basak, G.W.; Corbacioglu, S.; Duarte, R.; Bader, P.; Transplantation, Pediatric and Transplant Complications Working Parties of the European Society for Blood and Marrow.

In: Biology of Blood and Marrow Transplantation, Vol. 25, No. 9, 2019, p. 1786-1791.

Research output: Contribution to journalArticle

Faraci, M, Diesch, T, Labopin, M, Dalissier, A, Lankester, A, Gennery, A, Sundin, M, Uckan-Cetinkaya, D, Bierings, M, Peters, AMJ, Garwer, M, Schulz, A, Michel, G, Giorgiani, G, Gruhn, B, Locatelli, F, Giardino, S, Uyttebroeck, A, Rialland, F, Itäla-Remes, M, Dreger, P, Shaw, PJ, Bordon, V, Schlegel, PG, Mellgren, K, Moraleda, JM, Patrick, K, Schneider, P, Jubert, C, Lawitschka, A, Salooja, N, Basak, GW, Corbacioglu, S, Duarte, R, Bader, P & Transplantation, PATCWPOTESFBAM 2019, 'Gonadal Function after Busulfan Compared with Treosulfan in Children and Adolescents Undergoing Allogeneic Hematopoietic Stem Cell Transplant', Biology of Blood and Marrow Transplantation, vol. 25, no. 9, pp. 1786-1791. https://doi.org/10.1016/j.bbmt.2019.05.005
Faraci, M. ; Diesch, T. ; Labopin, M. ; Dalissier, A. ; Lankester, A. ; Gennery, A. ; Sundin, M. ; Uckan-Cetinkaya, D. ; Bierings, M. ; Peters, A.M.J. ; Garwer, M. ; Schulz, A. ; Michel, G. ; Giorgiani, G. ; Gruhn, B. ; Locatelli, F. ; Giardino, S. ; Uyttebroeck, A. ; Rialland, F. ; Itäla-Remes, M. ; Dreger, P. ; Shaw, P.J. ; Bordon, V. ; Schlegel, P.G. ; Mellgren, K. ; Moraleda, J.M. ; Patrick, K. ; Schneider, P. ; Jubert, C. ; Lawitschka, A. ; Salooja, N. ; Basak, G.W. ; Corbacioglu, S. ; Duarte, R. ; Bader, P. ; Transplantation, Pediatric and Transplant Complications Working Parties of the European Society for Blood and Marrow. / Gonadal Function after Busulfan Compared with Treosulfan in Children and Adolescents Undergoing Allogeneic Hematopoietic Stem Cell Transplant. In: Biology of Blood and Marrow Transplantation. 2019 ; Vol. 25, No. 9. pp. 1786-1791.
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title = "Gonadal Function after Busulfan Compared with Treosulfan in Children and Adolescents Undergoing Allogeneic Hematopoietic Stem Cell Transplant",
abstract = "Gonadal impairment is an important late effect with a significant impact on quality of life of transplanted patients. The aim of this study was to compare gonadal function after busulfan (Bu) or treosulfan (Treo) conditioning regimens in pre- and postpubertal children. This retrospective, multicenter study included children transplanted in pediatric European Society for Blood and Marrow Transplantation (EBMT) centers between 1992 and 2012 who did not receive gonadotoxic chemoradiotherapy before the transplant. We evaluated 137 patients transplanted in 25 pediatric EBMT centers. Median age at transplant was 11.04 years (range, 5 to 18); 89 patients were boys and 48 girls. Eighty-nine patients were prepubertal at transplant and 48 postpubertal. One hundred eighteen children received Bu and 19 Treo. A higher proportion of girls treated with Treo in the prepubertal stage reached spontaneous puberty compared with those treated with Bu (P = .02). Spontaneous menarche was more frequent after Treo than after Bu (P <.001). Postpubertal boys and girls treated with Treo had significantly lower luteinizing hormone levels (P = .03 and P = .04, respectively) compared with the Bu group. Frequency of gonadal damage associated with Treo was significantly lower than that observed after Bu. These results need to be confirmed in a larger population. {\circledC} 2019",
keywords = "Busulfan, Gonadal damage, Pubertal stage, Treosulfan, busulfan, estradiol, follitropin, gonadotropin, inhibin B, luteinizing hormone, Muellerian inhibiting factor, testosterone, treosulfan, adolescent, adult, allogeneic hematopoietic stem cell transplantation, Article, child, chronic myeloid leukemia, controlled study, female, follitropin blood level, follow up, gonad dysfunction, gonad function, gonadotropin blood level, hemophagocytic syndrome, hormone blood level, human, hypogonadism, juvenile myelomonocytic leukemia, luteinizing hormone blood level, major clinical study, male, menarche, multicenter study, pediatric patient, prepuberty, retrospective study, Shwachman syndrome, testosterone blood level, transplantation conditioning",
author = "M. Faraci and T. Diesch and M. Labopin and A. Dalissier and A. Lankester and A. Gennery and M. Sundin and D. Uckan-Cetinkaya and M. Bierings and A.M.J. Peters and M. Garwer and A. Schulz and G. Michel and G. Giorgiani and B. Gruhn and F. Locatelli and S. Giardino and A. Uyttebroeck and F. Rialland and M. It{\"a}la-Remes and P. Dreger and P.J. Shaw and V. Bordon and P.G. Schlegel and K. Mellgren and J.M. Moraleda and K. Patrick and P. Schneider and C. Jubert and A. Lawitschka and N. Salooja and G.W. Basak and S. Corbacioglu and R. Duarte and P. Bader and Transplantation, {Pediatric and Transplant Complications Working Parties of the European Society for Blood and Marrow}",
note = "Cited By :1 Export Date: 10 October 2019 CODEN: BBMTF Correspondence Address: Faraci, M.; Hematology/Oncology – Stem Cell Transplantation Unit, Istituto G. Gaslini, Largo G. Gaslini, 5, Italy; email: maurafaraci@alice.it Chemicals/CAS: busulfan, 55-98-1; estradiol, 50-28-2; follitropin, 9002-68-0; gonadotropin, 63231-54-9; inhibin B, 115088-91-0; luteinizing hormone, 39341-83-8, 9002-67-9; Muellerian inhibiting factor, 80497-65-0; testosterone, 58-22-0; treosulfan, 21106-06-9, 299-75-2 References: Tichelli, A., Rov{\'o}, A., Passweg, J., Late Effects Working Party of the European Group for Blood and Marrow Transplantation. Late complications after hematopoietic stem cell transplantation (2009) Expert Rev Hematol, 2, pp. 583-601; Bresters, D., Emons, J.A., Nuri, N., Ovarian insufficiency and pubertal development after hematopoietic stem cell transplantation in childhood (2014) Pediatr Blood Cancer, 61, pp. 2048-2053; Dvorak, C.C., Gracia, C.R., Sanders, J.E., NCI, NHLBI/PBMTC first international conference on late effects after pediatric hematopoietic cell transplantation: endocrine challenges-thyroid dysfunction, growth impairment, bone health, & reproductive risks (2011) Biol Blood Marrow Transplant, 17, pp. 1725-1738; Tauchmanov{\`a}, L., Selleri, C., Rosa, G.D., High prevalence of endocrine dysfunction in long-term survivors after allogeneic bone marrow transplantation for hematologic diseases (2002) Cancer, 95, pp. 1076-1084; Thibaud, E., Rodriguez-Macias, K., Trivin, C., Ovarian function after bone marrow transplantation during childhood (1998) Bone Marrow Transplant, 21, pp. 287-290; Cohen, A., B{\'e}k{\'a}ssy, A.N., Gaiero, A., EBMT Paediatric and Late Effects Working Parties. Endocrinological late complications after hematopoietic SCT in children (2008) Bone Marrow Transplant, 41, pp. S43-S48; Schneider, R.A., Schultze, J., Jensen, J.M., Long-term outcome after static intensity-modulated total body radiotherapy using compensators stratified by pediatric and adult cohorts (2008) Int J Radiat Oncol Biol Phys, 70, pp. 194-202; Bresters, D., Lawitschka, A., Cugno, C., Incidence and severity of crucial late effects after allogeneic HSCT for malignancy under the age of 3 years: TBI is what really matters (2016) Bone Marrow Transplant, 51, pp. 1482-1489; Faraci, M., Barra, S., Cohen, A., Very late nonfatal consequences of fractionated TBI in children undergoing bone marrow transplant (2005) Int J Radiat Oncol Biol Phys, 63, pp. 1568-1575; Sanders, J.E., Hawley, J., Levy, W., Pregnancies following high-dose cyclophosphamide with or without high-dose busulphan or total-body irradiation and bone marrow transplantation (1996) Blood, 87, pp. 3045-3052; Slatter, M.A., Boztug, H., P{\"o}tschger, U., EBMT Inborn Errors and Paediatric Diseases Working Parties. Treosulfan-based conditioning regimens for allogeneic haematopoietic stem cell transplantation in children with non-malignant diseases (2015) Bone Marrow Transplant, 50, pp. 1536-1541; Lehmberg, K., Albert, M.H., Beier, R., Treosulfan-based conditioning regimen for children and adolescents with hemophagocytic lymphohistiocytosis (2014) Haematologica, 99, pp. 180-184; Slatter, M.A., Rao, K., Abd Hamid, I.J., Treosulfan and fludarabine conditioning for hematopoietic stem cell transplantation in children with primary immunodeficiency: UK experience (2018) Biol Blood Marrow Transplant, 24, pp. 529-536; Greystoke, B., Bonanomi, S., Carr, T.F., Treosulfan-containing regimens achieve high rates of engraftment associated with low transplant morbidity and mortality in children with non-malignant disease and significant co-morbidities (2008) Br J Haematol, 142, pp. 257-262; Marzollo, A., Calore, E., Tumino, M., Treosulfan-based conditioning regimen in sibling and alternative donor hematopoietic stem cell transplantation for children with sickle cell disease (2017) J Med J Hematol Infect Dis, 9; Laporte, S., Couto-Silva, A.C., Trabado, S., Inhibin B and anti-M{\"u}llerian hormone as markers of gonadal function after hematopoietic cell transplantation during childhood (2011) BMC Pediatr, 11, p. 20; Bakker, B., Oostdijk, W., Bresters, D., Disturbances of growth and endocrine function after busulphan-based conditioning for haematopoietic stem cell transplantation during infancy and childhood (2004) Bone Marrow Transplant, 33, pp. 1049-1056; Grigg, A.P., McLachlan, R., Zaja, J., Reproductive status in long-term bone marrow transplant survivors receiving busulfan-cyclophosphamide (120 mg/kg) (2000) Bone Marrow Transplant, 26, pp. 1089-1095; Teinturier, C., Hartmann, O., Valteau-Couanet, D., Ovarian function after autologous bone marrow transplantation in childhood: high-dose busulphanis a major cause of ovarian failure (1998) Bone Marrow Transplant, 22, pp. 989-994; Panasiuk, A., Nussey, S., Veys, P., Gonadal function and fertility after stem cell transplantation in childhood: comparison of a reduced intensity conditioning regimen containing melphalan with a myeloablative regimen containing busulfan (2015) Br J Haematol, 170, pp. 719-726; Afify, Z., Shaw, P.J., Clavano-Harding, A., Cowell, C.T., Growth and endocrine function in children with acute myeloid leukaemia after bone marrow transplantation using busulfan/cyclophosphamide (2000) Bone Marrow Transplant, 25, pp. 1087-1092; Brachet, C., Heinrichs, C., Tenoutasse, S., Children with sickle cell disease: growth and gonadal function after hematopoietic stem cell transplantation (2007) J Pediatr Hematol Oncol, 29, pp. 445-450; Levi, M., Stemmer, S.M., Stein, J., Treosulfan induces distinctive gonadal toxicity compared with busulfan (2018) Oncotarget, 9, pp. 19317-19327; Vatanen, A., Wilhelmsson, M., Borgstr{\"o}m, B., Ovarian function after allogeneic hematopoietic stem cell transplantation in childhood and adolescence (2013) Eur J Endocrinol, 170, pp. 211-218; Ginsberg, J.P., New advances in fertility preservation for pediatric cancer patients (2011) Curr Opin Pediatr, 23, pp. 9-13; Green, D.M., Liu, W., Kutteh, W.H., Cumulative alkylating agent exposure and semen parameters in adult survivors of childhood cancer: a report from the St Jude Lifetime Cohort Study (2014) Lancet Oncol, 15, pp. 1215-1223; Chemaitilly, W., Li, Z., Krasin, M.J., Premature ovarian insufficiency in childhood cancer survivors: a report from the St. Jude Lifetime cohort (2017) J Clin Endocrinol Metab, 102, pp. 2242-2250",
year = "2019",
doi = "10.1016/j.bbmt.2019.05.005",
language = "English",
volume = "25",
pages = "1786--1791",
journal = "Biology of Blood and Marrow Transplantation",
issn = "1083-8791",
publisher = "Elsevier Inc.",
number = "9",

}

TY - JOUR

T1 - Gonadal Function after Busulfan Compared with Treosulfan in Children and Adolescents Undergoing Allogeneic Hematopoietic Stem Cell Transplant

AU - Faraci, M.

AU - Diesch, T.

AU - Labopin, M.

AU - Dalissier, A.

AU - Lankester, A.

AU - Gennery, A.

AU - Sundin, M.

AU - Uckan-Cetinkaya, D.

AU - Bierings, M.

AU - Peters, A.M.J.

AU - Garwer, M.

AU - Schulz, A.

AU - Michel, G.

AU - Giorgiani, G.

AU - Gruhn, B.

AU - Locatelli, F.

AU - Giardino, S.

AU - Uyttebroeck, A.

AU - Rialland, F.

AU - Itäla-Remes, M.

AU - Dreger, P.

AU - Shaw, P.J.

AU - Bordon, V.

AU - Schlegel, P.G.

AU - Mellgren, K.

AU - Moraleda, J.M.

AU - Patrick, K.

AU - Schneider, P.

AU - Jubert, C.

AU - Lawitschka, A.

AU - Salooja, N.

AU - Basak, G.W.

AU - Corbacioglu, S.

AU - Duarte, R.

AU - Bader, P.

AU - Transplantation, Pediatric and Transplant Complications Working Parties of the European Society for Blood and Marrow

N1 - Cited By :1 Export Date: 10 October 2019 CODEN: BBMTF Correspondence Address: Faraci, M.; Hematology/Oncology – Stem Cell Transplantation Unit, Istituto G. Gaslini, Largo G. Gaslini, 5, Italy; email: maurafaraci@alice.it Chemicals/CAS: busulfan, 55-98-1; estradiol, 50-28-2; follitropin, 9002-68-0; gonadotropin, 63231-54-9; inhibin B, 115088-91-0; luteinizing hormone, 39341-83-8, 9002-67-9; Muellerian inhibiting factor, 80497-65-0; testosterone, 58-22-0; treosulfan, 21106-06-9, 299-75-2 References: Tichelli, A., Rovó, A., Passweg, J., Late Effects Working Party of the European Group for Blood and Marrow Transplantation. Late complications after hematopoietic stem cell transplantation (2009) Expert Rev Hematol, 2, pp. 583-601; Bresters, D., Emons, J.A., Nuri, N., Ovarian insufficiency and pubertal development after hematopoietic stem cell transplantation in childhood (2014) Pediatr Blood Cancer, 61, pp. 2048-2053; Dvorak, C.C., Gracia, C.R., Sanders, J.E., NCI, NHLBI/PBMTC first international conference on late effects after pediatric hematopoietic cell transplantation: endocrine challenges-thyroid dysfunction, growth impairment, bone health, & reproductive risks (2011) Biol Blood Marrow Transplant, 17, pp. 1725-1738; Tauchmanovà, L., Selleri, C., Rosa, G.D., High prevalence of endocrine dysfunction in long-term survivors after allogeneic bone marrow transplantation for hematologic diseases (2002) Cancer, 95, pp. 1076-1084; Thibaud, E., Rodriguez-Macias, K., Trivin, C., Ovarian function after bone marrow transplantation during childhood (1998) Bone Marrow Transplant, 21, pp. 287-290; Cohen, A., Békássy, A.N., Gaiero, A., EBMT Paediatric and Late Effects Working Parties. Endocrinological late complications after hematopoietic SCT in children (2008) Bone Marrow Transplant, 41, pp. S43-S48; Schneider, R.A., Schultze, J., Jensen, J.M., Long-term outcome after static intensity-modulated total body radiotherapy using compensators stratified by pediatric and adult cohorts (2008) Int J Radiat Oncol Biol Phys, 70, pp. 194-202; Bresters, D., Lawitschka, A., Cugno, C., Incidence and severity of crucial late effects after allogeneic HSCT for malignancy under the age of 3 years: TBI is what really matters (2016) Bone Marrow Transplant, 51, pp. 1482-1489; Faraci, M., Barra, S., Cohen, A., Very late nonfatal consequences of fractionated TBI in children undergoing bone marrow transplant (2005) Int J Radiat Oncol Biol Phys, 63, pp. 1568-1575; Sanders, J.E., Hawley, J., Levy, W., Pregnancies following high-dose cyclophosphamide with or without high-dose busulphan or total-body irradiation and bone marrow transplantation (1996) Blood, 87, pp. 3045-3052; Slatter, M.A., Boztug, H., Pötschger, U., EBMT Inborn Errors and Paediatric Diseases Working Parties. Treosulfan-based conditioning regimens for allogeneic haematopoietic stem cell transplantation in children with non-malignant diseases (2015) Bone Marrow Transplant, 50, pp. 1536-1541; Lehmberg, K., Albert, M.H., Beier, R., Treosulfan-based conditioning regimen for children and adolescents with hemophagocytic lymphohistiocytosis (2014) Haematologica, 99, pp. 180-184; Slatter, M.A., Rao, K., Abd Hamid, I.J., Treosulfan and fludarabine conditioning for hematopoietic stem cell transplantation in children with primary immunodeficiency: UK experience (2018) Biol Blood Marrow Transplant, 24, pp. 529-536; Greystoke, B., Bonanomi, S., Carr, T.F., Treosulfan-containing regimens achieve high rates of engraftment associated with low transplant morbidity and mortality in children with non-malignant disease and significant co-morbidities (2008) Br J Haematol, 142, pp. 257-262; Marzollo, A., Calore, E., Tumino, M., Treosulfan-based conditioning regimen in sibling and alternative donor hematopoietic stem cell transplantation for children with sickle cell disease (2017) J Med J Hematol Infect Dis, 9; Laporte, S., Couto-Silva, A.C., Trabado, S., Inhibin B and anti-Müllerian hormone as markers of gonadal function after hematopoietic cell transplantation during childhood (2011) BMC Pediatr, 11, p. 20; Bakker, B., Oostdijk, W., Bresters, D., Disturbances of growth and endocrine function after busulphan-based conditioning for haematopoietic stem cell transplantation during infancy and childhood (2004) Bone Marrow Transplant, 33, pp. 1049-1056; Grigg, A.P., McLachlan, R., Zaja, J., Reproductive status in long-term bone marrow transplant survivors receiving busulfan-cyclophosphamide (120 mg/kg) (2000) Bone Marrow Transplant, 26, pp. 1089-1095; Teinturier, C., Hartmann, O., Valteau-Couanet, D., Ovarian function after autologous bone marrow transplantation in childhood: high-dose busulphanis a major cause of ovarian failure (1998) Bone Marrow Transplant, 22, pp. 989-994; Panasiuk, A., Nussey, S., Veys, P., Gonadal function and fertility after stem cell transplantation in childhood: comparison of a reduced intensity conditioning regimen containing melphalan with a myeloablative regimen containing busulfan (2015) Br J Haematol, 170, pp. 719-726; Afify, Z., Shaw, P.J., Clavano-Harding, A., Cowell, C.T., Growth and endocrine function in children with acute myeloid leukaemia after bone marrow transplantation using busulfan/cyclophosphamide (2000) Bone Marrow Transplant, 25, pp. 1087-1092; Brachet, C., Heinrichs, C., Tenoutasse, S., Children with sickle cell disease: growth and gonadal function after hematopoietic stem cell transplantation (2007) J Pediatr Hematol Oncol, 29, pp. 445-450; Levi, M., Stemmer, S.M., Stein, J., Treosulfan induces distinctive gonadal toxicity compared with busulfan (2018) Oncotarget, 9, pp. 19317-19327; Vatanen, A., Wilhelmsson, M., Borgström, B., Ovarian function after allogeneic hematopoietic stem cell transplantation in childhood and adolescence (2013) Eur J Endocrinol, 170, pp. 211-218; Ginsberg, J.P., New advances in fertility preservation for pediatric cancer patients (2011) Curr Opin Pediatr, 23, pp. 9-13; Green, D.M., Liu, W., Kutteh, W.H., Cumulative alkylating agent exposure and semen parameters in adult survivors of childhood cancer: a report from the St Jude Lifetime Cohort Study (2014) Lancet Oncol, 15, pp. 1215-1223; Chemaitilly, W., Li, Z., Krasin, M.J., Premature ovarian insufficiency in childhood cancer survivors: a report from the St. Jude Lifetime cohort (2017) J Clin Endocrinol Metab, 102, pp. 2242-2250

PY - 2019

Y1 - 2019

N2 - Gonadal impairment is an important late effect with a significant impact on quality of life of transplanted patients. The aim of this study was to compare gonadal function after busulfan (Bu) or treosulfan (Treo) conditioning regimens in pre- and postpubertal children. This retrospective, multicenter study included children transplanted in pediatric European Society for Blood and Marrow Transplantation (EBMT) centers between 1992 and 2012 who did not receive gonadotoxic chemoradiotherapy before the transplant. We evaluated 137 patients transplanted in 25 pediatric EBMT centers. Median age at transplant was 11.04 years (range, 5 to 18); 89 patients were boys and 48 girls. Eighty-nine patients were prepubertal at transplant and 48 postpubertal. One hundred eighteen children received Bu and 19 Treo. A higher proportion of girls treated with Treo in the prepubertal stage reached spontaneous puberty compared with those treated with Bu (P = .02). Spontaneous menarche was more frequent after Treo than after Bu (P <.001). Postpubertal boys and girls treated with Treo had significantly lower luteinizing hormone levels (P = .03 and P = .04, respectively) compared with the Bu group. Frequency of gonadal damage associated with Treo was significantly lower than that observed after Bu. These results need to be confirmed in a larger population. © 2019

AB - Gonadal impairment is an important late effect with a significant impact on quality of life of transplanted patients. The aim of this study was to compare gonadal function after busulfan (Bu) or treosulfan (Treo) conditioning regimens in pre- and postpubertal children. This retrospective, multicenter study included children transplanted in pediatric European Society for Blood and Marrow Transplantation (EBMT) centers between 1992 and 2012 who did not receive gonadotoxic chemoradiotherapy before the transplant. We evaluated 137 patients transplanted in 25 pediatric EBMT centers. Median age at transplant was 11.04 years (range, 5 to 18); 89 patients were boys and 48 girls. Eighty-nine patients were prepubertal at transplant and 48 postpubertal. One hundred eighteen children received Bu and 19 Treo. A higher proportion of girls treated with Treo in the prepubertal stage reached spontaneous puberty compared with those treated with Bu (P = .02). Spontaneous menarche was more frequent after Treo than after Bu (P <.001). Postpubertal boys and girls treated with Treo had significantly lower luteinizing hormone levels (P = .03 and P = .04, respectively) compared with the Bu group. Frequency of gonadal damage associated with Treo was significantly lower than that observed after Bu. These results need to be confirmed in a larger population. © 2019

KW - Busulfan

KW - Gonadal damage

KW - Pubertal stage

KW - Treosulfan

KW - busulfan

KW - estradiol

KW - follitropin

KW - gonadotropin

KW - inhibin B

KW - luteinizing hormone

KW - Muellerian inhibiting factor

KW - testosterone

KW - treosulfan

KW - adolescent

KW - adult

KW - allogeneic hematopoietic stem cell transplantation

KW - Article

KW - child

KW - chronic myeloid leukemia

KW - controlled study

KW - female

KW - follitropin blood level

KW - follow up

KW - gonad dysfunction

KW - gonad function

KW - gonadotropin blood level

KW - hemophagocytic syndrome

KW - hormone blood level

KW - human

KW - hypogonadism

KW - juvenile myelomonocytic leukemia

KW - luteinizing hormone blood level

KW - major clinical study

KW - male

KW - menarche

KW - multicenter study

KW - pediatric patient

KW - prepuberty

KW - retrospective study

KW - Shwachman syndrome

KW - testosterone blood level

KW - transplantation conditioning

U2 - 10.1016/j.bbmt.2019.05.005

DO - 10.1016/j.bbmt.2019.05.005

M3 - Article

VL - 25

SP - 1786

EP - 1791

JO - Biology of Blood and Marrow Transplantation

JF - Biology of Blood and Marrow Transplantation

SN - 1083-8791

IS - 9

ER -