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

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.

Ocular symptoms in children treated with human-mouse chimeric anti-GD2 mAb ch14.18 for neuroblastoma.

Unusual ocular symptoms observed during intravenous treatment with anti-disialoganglioside antibody (Ab) in children suffering from neuroblastoma were analyzed and the results reported. Within the framework of the German Collaborative Neuroblastoma Study NB97, 85 children with high-risk neuroblastoma received anti-GD2 monoclonal antibody ch14.18 intravenously. Side effects were regularly reported to the study center. Ocular symptoms were recorded in clinical detail, duration and development over time. Symptoms of a parasympathetic deficit corresponding to internal ophthalmoplegia, i.e. mydriasis and accommodation deficit, were found in 10 patients. They were uni- or bilateral, began after the termination of Ab infusion and improved or disappeared in all surviving children. They did not reappear or worsen upon repeated Ab infusions. The pathophysiology of these disorders remains poorly understood. It is concluded that during systemic treatment with the anti-GD2 antibody ch14.18, reversible symptoms of parasympathetic denervation of the eye may occur which, however, do not warrant termination of this treatment.