Treatment of acquired hemophilia by the Bonn-Malmo Protocol: documentation of an in vivo immunomodulating concept.
Acquired hemophilia (AH) is an extremely rare condition in which autoantibodies (inhibitors) against clotting factor VIII induce acute and life-threatening hemorrhagic diathesis because of abnormal blood clotting. The mortality rate of AH is as high as 16%, and current treatment options are associated with adverse side effects. We investigated a therapeutic approach for AH called the modified Bonn-Malmo Protocol (MBMP). The aims of MBMP include suppression of bleeding, permanent elimination of inhibitors, and development of immune tolerance, thereby avoiding long-term reliance on coagulation products. The protocol included immunoadsorption for inhibitor elimination, factor VIII substitution, intravenous immunoglobulin, and immunosuppression. Thirty-five high-titer patients with critical bleeding who underwent MBMP were evaluated. Bleeding was rapidly controlled during 1 or 2 apheresis sessions, and no subsequent bleeding episodes occurred. Inhibitor levels decreased to undetectable levels within a median of 3 days (95% confidence interval [95% CI], 2-4 days), factor substitution was stopped within a median of 12 days (95% CI, 11-17 days), and treatment was completed within a median of 14 days (95% CI, 12-17 days). Long-term follow-up (7 months-7 years) showed an overall response rate of 88% for complete remission (CR). When cancer patients were excluded, the CR rate was 97%.
Zeitler
Heike
H
Medical Policlinic, University of Bonn, Wilhelmstrasse 35-37, 53111 Bonn, Germany. heike.zeitler@uni-bonn.de
Ulrich-Merzenich
Gudrun
G
Hess
Lothar
L
Konsek
Eligius
E
Unkrig
Christoph
C
Walger
Peter
P
Vetter
Hans
H
Brackmann
Hans-Hermann
HH
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001323:Autoantibodies / Q000097:blood; D001327:Autoimmune Diseases / Q000097:blood / Q000401:mortality / Q000628:therapy*; D001781:Blood Component Removal; D003520:Cyclophosphamide / Q000008:administration & dosage*; D018572:Disease-Free Survival; D004338:Drug Combinations; D005164:Factor IX / Q000008:administration & dosage*; D005167:Factor VII / Q000008:administration & dosage*; D005169:Factor VIII / Q000008:administration & dosage* / Q000032:analysis / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D006467:Hemophilia A / Q000097:blood / Q000401:mortality / Q000628:therapy*; D006470:Hemorrhage / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects; D007074:Immunoglobulin G / Q000008:administration & dosage*; D016756:Immunoglobulins, Intravenous / Q000008:administration & dosage; D007155:Immunologic Factors / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D012074:Remission Induction; D012189:Retrospective Studies; D015996:Survival Rate
D001323:Autoantibodies; D004338:Drug Combinations; D007074:Immunoglobulin G; D016756:Immunoglobulins, Intravenous; D007155:Immunologic Factors; D003520:Cyclophosphamide; D005167:Factor VII; D005169:Factor VIII; D005164:Factor IX