title: Treatment of the bone marrow failure in Fanconi anemia patients with danazol.
abstract: More than 90% of Fanconi anemia (FA) patients experience progressive bone marrow failure during life with a median onset at 8 years of age. As matched sibling donor transplantation as preferred treatment is not available for the majority of patients, several synthetic androgens have been used as short-term treatment options for the marrow failure in FA patients for more than 50 years. Here, we retrospectively collected data on eight FA patients who received danazol for the off-label treatment of their marrow failure at a starting dose of approximately 5mg/kg body weight/die. The hematological parameters at the initiation of treatment were hemoglobin (Hb) <8 g/dL and/or thrombocytes <30,000/μl. In 7 out of 8 FA patients, the values for both parameters rose on average >50% over the starting counts within 6 months and remained stable for up to 3 years despite careful reduction of the danazol dose per kg body weight. In 4 patients with a follow-up of 3 years, the platelets finally reached an average of 68,000/μL or 2.8 times over the starting values, while the Hb remained stable >11 g/dL. Danazol was reduced to 54% of the starting dose or 2.6 mg/kg/die. One FA-A patient with an unusually severe phenotype did not response with her PB counts to either danazol or oxymethalone within 6 months. None of the patients developed severe or unacceptable side-effects from the danazol treatment that led to the discontinuation of therapy. This initial description suggests that danazol might be an effective and well-tolerated treatment option for delaying the progressive marrow failure in FA patients for at least 3 years and longer.
authors.affiliation: Otorhinolaryngology (HNO), Heinrich Heine University, Düsseldorf, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Scheckenbach
authors.forename: Mary
authors.initials: M
authors.lastname: Morgan
authors.forename: Judith
authors.initials: J
authors.lastname: Filger-Brillinger
authors.forename: Matthias
authors.initials: M
authors.lastname: Sandmann
authors.forename: Bruce
authors.initials: B
authors.lastname: Strimling
authors.forename: Wolfram
authors.initials: W
authors.lastname: Scheurlen
authors.forename: Detlev
authors.initials: D
authors.lastname: Schindler
authors.forename: Ulrich
authors.initials: U
authors.lastname: Göbel
authors.forename: Helmut
authors.initials: H
authors.lastname: Hanenberg
mesh_terms: D000293:Adolescent; D000328:Adult; D001772:Blood Cell Count; D001853:Bone Marrow / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D003613:Danazol / Q000627:therapeutic use*; D004965:Estrogen Antagonists / Q000627:therapeutic use*; D005199:Fanconi Anemia / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D009154:Mutation; D055815:Young Adult
chemical_list: D004965:Estrogen Antagonists; D003613:Danazol