title: Treatment of diffuse alveolar hemorrhage after allogeneic bone marrow transplant with recombinant factor VIIa.
abstract: Diffuse alveolar hemorrhage (DAH) is a potentially life-threatening pulmonary toxicity that occurs in 1-21% of patients following bone marrow transplantation. The syndrome is associated with a high mortality rate; and current treatment options are limited. Recombinant factor VIIa (rFVIIa, Novoseven) has recently been approved for the treatment of bleeding in patients with hemophilia A/B with inhibitors. A greater understanding of the mechanism by which rFVIIa restores hemostasis has recently become available; with in vitro evidence supporting that the thrombin burst achieved by rFVIIa is independent of the presence or binding to tissue factor. This insight has suggested a range of other potential clinical uses for the drug; including the setting of pulmonary hemorrhage. We review our experience with using rFVIIa for treatment of DAH in a patient with acute myelogenous leukemia following a matched unrelated donor bone marrow transplant. Boluses of 90 microg/kg rFVIIa were given every 3 h x 4 doses/day, concurrently with high-dose corticosteroids and maintenance of a platelet count >50 000/mm(3). Rapid clinical and radiological improvement was noted within several doses of rFVIIa, with discontinuation of the drug after eight doses. However, the patient's clinical condition began to rapidly deteriorate following cessation of rVIIa, resulting in reinstitution of therapy 24 h later. The patient again exhibited rapid clinical improvement; and rFVIIa was continued for an additional 16 doses with no further evidence of pulmonary hemorrhage noted. No toxicity or adverse events were observed with rFVIIa treatment. Our experience indicates that rFVIIa may be an effective treatment option for DAH post bone marrow transplant; although further clinical studies are needed before recommendations can be made regarding off label use of rFVIIa in this clinical setting.
authors.affiliation: Department of Blood and Marrow Transplantation, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: K
authors.initials: K
authors.lastname: Hicks
authors.forename: D
authors.initials: D
authors.lastname: Peng
authors.forename: J L
authors.initials: JL
authors.lastname: Gajewski
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D003561:Cytarabine / Q000008:administration & dosage / Q000009:adverse effects; D015942:Factor VIIa / Q000627:therapeutic use*; D017809:Fatal Outcome; D005260:Female; D006470:Hemorrhage / Q000209:etiology / Q000628:therapy*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D015479:Leukemia, Myelomonocytic, Acute / Q000150:complications / Q000188:drug therapy / Q000628:therapy*; D008171:Lung Diseases / Q000209:etiology / Q000628:therapy*; D011030:Pneumothorax / Q000209:etiology; D011650:Pulmonary Alveoli; D011994:Recombinant Proteins / Q000627:therapeutic use; D019772:Topotecan / Q000008:administration & dosage / Q000009:adverse effects; D019172:Transplantation Conditioning / Q000009:adverse effects; D014184:Transplantation, Homologous / Q000009:adverse effects*; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives*
chemical_list: D007166:Immunosuppressive Agents; D011994:Recombinant Proteins; D003561:Cytarabine; D019772:Topotecan; D003520:Cyclophosphamide; D015942:Factor VIIa; D014740:Vidarabine; C024352:fludarabine