Superior in vivo response of recombinant factor VIII concentrate in children with hemophilia A.

OBJECTIVE: Our previous experience with highly purified plasma-derived factor VIII (pdFVIII) concentrates showed that adult dosage recommendations were not applicable to children. In this study, we compared the in vivo response and recovery of recombinant factor VIII (rFVIII) with those of highly purified pdFVIII concentrate in children with hemophilia A. STUDY DESIGN: Ten boys with severe factor VIII deficiency and no concurrent bleeding episodes participated in a masked, prospective, crossover study comparing factor VIII coagulant activity after infusion of 50 units of pdFVIII and rFVIII products per kilogram of body weight. RESULTS: Mean peak factor VIII response with rFVIII was 1.91% +/- 0.14%, significantly better than the response observed with highly purified pdFVIII of 1.5% +/- 0.15% (p = 0.007). Mean peak factor VIII recovery was 100.5% with rFVIII versus 78.7% with pdFVIII (p = 0.007). Positive correlations between response to rFVIII and body surface area (r = 0.734, p = 0.015), body weight (r = 0.762, p = 0.01), and plasma volume (r = 0.659, p = 0.03) were observed. CONCLUSIONS: Infusion of rFVIII produced a significantly better response and recovery in vivo than infusion of highly purified pdFVIII in children. The response in children after infusion of rFVIII was similar to the response previously observed in adults.

Successful in vivo immunolocalization of Langerhans cell histiocytosis with use of a monoclonal antibody, NA1/34.

The antibody NA1/34 is a murine monoclonal antibody directed against the CD1a surface antigen expressed on normal Langerhans cells, cortical thymocytes, and on lesional cells in Langerhans cell histiocytosis (LCH). Our hypothesis was that NA1/34 would localize sites of disease activity in patients with multisystem LCH. To test this hypothesis, indium 111-labeled NA1/34 was administered to five patients with multisystem LCH and serial gamma scans were obtained for up to 120 hours. Serial serum samples were obtained from one patient for analysis of anti-mouse Ig antibody and NA1/34 levels. Direct and indirect immunofluorescence staining for CD1a and NA1/34 were performed on a tissue biopsy specimen from one patient after administration of the antibody. The 1- and 4-hour scans showed distribution of antibody in the blood pool, but in later scans localization of the antibody was noted in areas of known disease activity in all five patients. Bony lesions, previously seen on skeletal radiographs, were especially well identified. Serum kinetics studies showed clearance of the antibody from the blood pool within 12 hours of administration. Direct binding of NA1/34 to lesional cells was demonstrated by direct immunofluorescence. The only adverse effect was urticaria in one patient. We conclude that NA1/34 localizes disease activity in vivo in bones of patients with LCH with minimal toxic effects. An evaluation of its role in determining disease extent ("staging") and in treatment is now needed.