Off-label use of recombinant factor VIIa in patients following bone marrowtransplantation

Recombinant factor VIIa (rFVIIa, NovoSeven) is FDA-approved for the treatme nt of bleeding in patients with hemophilia A/B with inhibitors. A growing l iterature suggests that there may be expanded indications for the use of No voSeven in patients with significant bleeding who do not have a known facto r deficiency. Severe bleeding refractory to standard hematologic or hemosta tic support is common in patients undergoing bone marrow transplantation (B MT). We review our experience with rFVIIa in three patients (8 years 8 mont hs to 19 years, median 13 years) treated for pulmonary hemorrhage (n = 1), hemorrhagic cystitis (n = 3), and gastrointestinal bleeding (n = 2). Boluse s of 90-270 mug/kg rVIIa with subsequent doses of 90 mug/kg every 4-24 h fo r 3-14 days were given, concurrent with maintaining platelet counts > 50 00 0/mm(3). Transient clinical responses in gross hematuria (two patients) and in pulmonary hemorrhage were noted within several days of starting rFVIIa, but bleeding in a new site in two patients and renewed bleeding of the ini tial site in the third resulted in discontinuation of the drug. No toxicity or adverse events were observed while the patients were on rFVIIa treatmen t. Because of the substantial cost of this product, the lack of adequate mo nitoring methodology, and the variability of current dose and dosing interv als, large randomized studies are needed before definitive off-label use in the setting of BMT can be recommended.