Combined immunosuppression for acquired hemophilia A: CyDRi is a highly effective low-toxicity regimen

• Type of Material: Article
• Authors: Barbar Simon, Semmelweis University; Andrea Ceglédi, National Institute of Hematology and Infectious Disease; János Dolgos, National Institute of Hematology and Infectious Disease; Péter Farkas, Semmelweis University; Manila Gaddh, Emory University; László Hankó, Semmelweis University; Robert Horváth, Semmelweis University; Ambrus Kaposi, ELTE; Lászlóné Magyar, National Institute of Hematology and Infectious Disease; Tamás last name, Semmelweis University; Attila Szederjesi, Semmelweis University; Nikolett Wohner, Semmelweis University; Imre Bodo, Emory University
• Language: English
• Date: 2022-08-09
• Publisher: The American Society of Hematology
• Publication Version: Final Published Version
• Copyright Statement: © 2022 by The American Society of Hematology.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): https://doi.org/10.1182/blood.2022016873
• Title of Journal or Parent Work: blood
• Volume: 140
• Issue: 18
• Start Page: 1983
• End Page: 1992
• Grant/Funding Information: This work was partially supported by the Hungarian National Research Development and Innovation Office (NFKI) grant OTKA-K19_131945 (I.B.).
• Keywords: immunosuppressive regimen; autoimmune bleeding disorder; Acquired hemophilia A
• Research Categories: Health Sciences, Immunology; Health Sciences, Medicine and Surgery

Abstract

Acquired hemophilia A (AHA) is a rare severe autoimmune bleeding disorder with significant morbidity and mortality. Although critical for disease control, there is no consensus for the best immunosuppressive regimen. Most authors use steroids first line, followed by other agents for steroid failures. Upfront combined regimens offer the advantage of reduced steroid exposure and toxicity as well as increased efficacy. We retrospectively analyzed data from 32 patients with AHA treated on an identical such institutional protocol: cyclophosphamide 1000 mg on days 1 and 22, dexamethasone 40 mg on days 1, 8, 15, and 22, and rituximab 100 mg on days 1, 8, 15, and 22 (the regimen was termed CyDRi). All patients received at least 1 cycle of CyDRi. If necessary, CyDRi was repeated until remission, no sooner than day 43 of the previous cycle. Bleeding control was rapidly achieved. The median time for bleeding control was 15.5 days (range, 0-429 days; interquartile range, 2.5-29.5 days). Thirty-one (96.8%) of 32 patients achieved durable complete remission (CR); 29 (90.6%) of 32 patients were alive at last follow-up, all of them in CR. The median time to reach first CR was 77 days (range, 19-939 days; interquartile range, 31-115 days). Toxicity and side effects were acceptable and milder than those of commonly used, prolonged steroid therapies. In conclusion, the CyDRi regimen produced markedly higher CR rates and overall survival than currently used sequential regimens. Taken together, CyDRi proved to be an attractive option for the immunosuppression of elderly patients with AHA.