Androgen therapy in inherited bone marrow failure syndromes: analysis from the Canadian Inherited Marrow Failure Registry

Albert Català; Salah S Ali; Geoffrey D E Cuvelier; MacGregor Steele; Robert J Klaassen; Conrad V Fernandez; Yves D Pastore; Sharon Abish; Meera Rayar; Lawrence Jardine; Vicky R Breakey; Josee Brossard; Roona Sinha; Mariana Silva; Lisa Goodyear; Jeffrey H Lipton; Bruno Michon; Catherine Corriveau-Bourque; Lillian Sung; Supanun Lauhasurayotin; Bozana Zlateska; Michaela Cada; Yigal Dror

doi:10.1111/bjh.16445

Androgen therapy in inherited bone marrow failure syndromes: analysis from the Canadian Inherited Marrow Failure Registry

Br J Haematol. 2020 Jun;189(5):976-981. doi: 10.1111/bjh.16445. Epub 2020 Mar 3.

Authors

Albert Català¹, Salah S Ali², Geoffrey D E Cuvelier³, MacGregor Steele⁴, Robert J Klaassen⁵, Conrad V Fernandez⁶, Yves D Pastore⁷, Sharon Abish⁸, Meera Rayar⁹, Lawrence Jardine¹⁰, Vicky R Breakey¹¹, Josee Brossard¹², Roona Sinha¹³, Mariana Silva¹⁴, Lisa Goodyear¹⁵, Jeffrey H Lipton¹⁶, Bruno Michon¹⁷, Catherine Corriveau-Bourque¹⁸, Lillian Sung¹⁹, Supanun Lauhasurayotin^{1

20}, Bozana Zlateska¹, Michaela Cada¹, Yigal Dror^{1

20

21}

Affiliations

¹ Division of Hematology/Oncology, Department of Pediatrics, Marrow Failure and Myelodysplasia Program, The Hospital for Sick Children, Toronto, ON, Canada.
² Bone Marrow Transplantation and Cellular Therapy, Division of Hematology/Oncology, Department of Pediatrics, The Hospital for Sick Children, Toronto, ON, Canada.
³ Pediatric Hematology-Oncology-Blood and Marrow Transplantation, University of Manitoba, CancerCare Manitoba, Winnipeg, MB, Canada.
⁴ Alberta Children's Hospital, Calgary, AB, Canada.
⁵ Department of Pediatrics, Children's Hospital of Eastern Ontario, Ottawa, ON, Canada.
⁶ Pediatric Hematology/Oncology, IWK Health Centre, Halifax, NS, Canada.
⁷ CHU Sainte-Justine, Montreal, QC, Canada.
⁸ Pediatric Hematology Oncology, Montreal Children's Hospital, Montreal, QC, Canada.
⁹ Division of Hematology/Oncology, UBC & B.C. Children's Hospital, Vancouver, BC, Canada.
¹⁰ Children's Hospital, London Health Sciences Centre, London, ON, Canada.
¹¹ Department of Pediatrics, McMaster University, Hamilton, ON, Canada.
¹² Centre Hospitalier Universitaire, Sherbrooke, QC, Canada.
¹³ Royal University Hospital, Saskatoon, SK, Canada.
¹⁴ Kingston General Hospital, Kingston, ON, Canada.
¹⁵ Pediatric Hematology/Oncology, Janeway Child Health Centre, St. John's, NF, Canada.
¹⁶ Allogeneic Blood and Marrow Transplant Program, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada.
¹⁷ Centre Hospitalier Universitaire de Quebec, Sainte-Foy, QC, Canada.
¹⁸ Pediatrics, University of Alberta, Edmonton, AB, Canada.
¹⁹ Division of Hematology/Oncology, Department of Pediatrics, Child and Population Health Sciences, Research Institute, The Hospital for Sick Children, Toronto, ON, Canada.
²⁰ Genetics and Genome Biology Program, The Hospital for Sick Children, Toronto, ON, Canada.
²¹ Institute of Medical Science, University of Toronto, Toronto, ON, Canada.

PMID: 32128787
DOI: 10.1111/bjh.16445

Abstract

Progressive cytopenia is a serious complication among paediatric patients with inherited bone marrow failure syndromes (IBMFS). Androgens have been used to improve blood counts in different bone marrow failure conditions. Little is known about efficacy and toxicity with new androgens (i.e., danazol) in different types of IBMFS. We identified 29 patients from the Canadian Inherited Marrow Failure Registry, who received oxymetholone or danazol. Sixteen (55%) had haematological response including patients with unclassified IBMFS (45%). Danazol showed a better toxicity profile and similar efficacy compared to oxymetholone. Androgens are an effective and safe option to ameliorate bone marrow failure in IBMFS.

Keywords: Fanconi anaemia; androgens; bone marrow failure; danazol; dyskeratosis congenita.

MeSH terms

Adolescent
Adult
Androgens / adverse effects
Androgens / therapeutic use*
Bone Marrow Failure Disorders / blood
Bone Marrow Failure Disorders / drug therapy*
Bone Marrow Failure Disorders / genetics
Bone Marrow Failure Disorders / therapy
Canada / epidemiology
Cell Lineage
Child
Child, Preschool
Combined Modality Therapy
Danazol / adverse effects
Danazol / therapeutic use
Disease Progression
Drug Substitution
Female
Hematopoietic Stem Cell Transplantation
Humans
Infant
Male
Middle Aged
Oxymetholone / adverse effects
Oxymetholone / therapeutic use
Pancytopenia / drug therapy
Pancytopenia / etiology
Registries
Thrombocytopenia / drug therapy
Thrombocytopenia / etiology
Treatment Outcome
Virilism / chemically induced

Substances

Androgens
Oxymetholone
Danazol