Treatment of the bone marrow failure in Fanconi anemia patients with danazol

Kathrin Scheckenbach, Mary Morgan, Judith Filger-Brillinger, Matthias Sandmann, Bruce Strimling, Wolfram Scheurlen, Detlev Schindler, Ulrich Göbel, Helmut Hanenberg

Research output: Contribution to journalArticle

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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 5. mg/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.

Original languageEnglish
Pages (from-to)128-131
Number of pages4
JournalBlood Cells, Molecules and Diseases
Volume48
Issue number2
DOIs
StatePublished - Feb 15 2012

Fingerprint

Danazol
Fanconi Anemia
Bone Marrow
Therapeutics
Oxymetholone
Hemoglobins
Testosterone Congeners
Body Weight
Siblings
Blood Platelets
Transplantation
Tissue Donors
Phenotype

Keywords

  • Androgen
  • Bone marrow failure
  • Danazol
  • Fanconi anemia
  • Treatment

ASJC Scopus subject areas

  • Molecular Biology
  • Molecular Medicine
  • Hematology
  • Cell Biology

Cite this

Scheckenbach, K., Morgan, M., Filger-Brillinger, J., Sandmann, M., Strimling, B., Scheurlen, W., ... Hanenberg, H. (2012). Treatment of the bone marrow failure in Fanconi anemia patients with danazol. Blood Cells, Molecules and Diseases, 48(2), 128-131. https://doi.org/10.1016/j.bcmd.2011.11.006

Treatment of the bone marrow failure in Fanconi anemia patients with danazol. / Scheckenbach, Kathrin; Morgan, Mary; Filger-Brillinger, Judith; Sandmann, Matthias; Strimling, Bruce; Scheurlen, Wolfram; Schindler, Detlev; Göbel, Ulrich; Hanenberg, Helmut.

In: Blood Cells, Molecules and Diseases, Vol. 48, No. 2, 15.02.2012, p. 128-131.

Research output: Contribution to journalArticle

Scheckenbach, K, Morgan, M, Filger-Brillinger, J, Sandmann, M, Strimling, B, Scheurlen, W, Schindler, D, Göbel, U & Hanenberg, H 2012, 'Treatment of the bone marrow failure in Fanconi anemia patients with danazol', Blood Cells, Molecules and Diseases, vol. 48, no. 2, pp. 128-131. https://doi.org/10.1016/j.bcmd.2011.11.006
Scheckenbach K, Morgan M, Filger-Brillinger J, Sandmann M, Strimling B, Scheurlen W et al. Treatment of the bone marrow failure in Fanconi anemia patients with danazol. Blood Cells, Molecules and Diseases. 2012 Feb 15;48(2):128-131. https://doi.org/10.1016/j.bcmd.2011.11.006
Scheckenbach, Kathrin ; Morgan, Mary ; Filger-Brillinger, Judith ; Sandmann, Matthias ; Strimling, Bruce ; Scheurlen, Wolfram ; Schindler, Detlev ; Göbel, Ulrich ; Hanenberg, Helmut. / Treatment of the bone marrow failure in Fanconi anemia patients with danazol. In: Blood Cells, Molecules and Diseases. 2012 ; Vol. 48, No. 2. pp. 128-131.
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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 5. mg/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.",
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