Abstract
Background:
Acquired hemophilia A (AHA) is a rare bleeding disorder in which inhibitory antibodies neutralize factor VIII (FVIII) activity, leading to high morbidity and mortality. Although the standard of care is immunosuppressive treatment (IST) to eradicate inhibitors, there are no specific guidelines for the best immunosuppressive regimen, especially for relapsing patients. Recently, the reported upfront combined CyDRi regimen from Hungary has produced markedly higher complete remission (CR) rates and overall survival (OS) than currently used sequential regimens for newly diagnosed patients. This retrospective study aimed to investigate the efficacy and safety of RCD pulse regimen (similar to the CyDRi ) for AHA.
Methods:
From October 2024 to July 2025, a total of 8 patients with AHA (including 4 relapsed patients and 4 newly diagnosed patients) in our center were enrolled in this study, and received at least 1 course of RCD. The RCD pulse regimen is a combined immunosuppressive therapy (IST) consisting of: 500mg cyclophosphamide intravenously on days 1, 8, 15, and 22; 40mg dexamethasone, intravenously or orally, on days 1, 8, 15, and 22; and 100mg rituximab intravenously on days 1, 8, 15, and 22. When necessary, RCD was repeated no earlier than day 43 of the previous cycle if a complete response (CR) was not achieved. All patients received infection prophylaxis with sulfamethoxazole and trimethoprim (480 mg once daily) and acyclovir (400 mg once daily). Ethical approval and informed consent were obtained for this study.
Results:
Among the 8 included patients, 6 were male and 2 were female, with ages ranging from 31 to 90 years old. The median time from the first symptom to diagnosis was 2 months (range, 1 - 12 months). Comorbidities included nephrotic syndrome, hemorrhoids, diabetes mellitus, breast cancer, arrhythmia, headache, cardiac pacemaker implantation, prostatic hyperplasia, bilateral renal cysts, knee arthritis, osteoporosis, cataract, hypertension, coronary heart disease, depression, and interstitial pneumonia. An underlying disease was identified in 2 patients (25%), both with interstitial pneumonia, and one of them also had unclassified rheumatism; the remaining 6 cases (75%) were considered idiopathic. Except for 1 patient without bleeding manifestations, the other 7 cases all had skin ecchymoses, 4 had muscle hematomas, 2 had joint bleeding, and 1 had recurrent upper gastrointestinal bleeding. Of the 8 patients, 4 (50%) presented with active bleeding requiring bypassing agents (administered concurrently with the RCD regimen) from admission until bleeding was controlled. The remaining 4 patients had a recent history of bleeding but were not actively bleeding at admission and received RCD without concurrent bypassing agents.
The median time for bleeding control after RCD treatment was 1.5 weeks (range, 0 - 3 weeks). The median value of FVIII activity at diagnosis was 1.8 IU/dL (range, 0.1 - 2.6 IU/dL), and the median initial inhibitor titer was 48.65 BU (range, 7.5 - 131 BU). Among the 8 patients, 6 (75%) had initial Bethesda titers > 20 BU, while 5 (62.5%) had initial Bethesda titers > 20 BU before receiving RCD treatment. Two patients with inhibitors > 100 BU and 2 patients with inhibitors < 20 BU did not achieve CR after prednisolone alone or combination therapy with the addition of cyclophosphamide prior to RCD.
To date, 7 of the 8 (87.5%) patients have achieved CR after 1 or 2 courses of RCD (3 newly diagnosed patients after 1 courses of RCD, 1 newly diagnosed patient and 3 relapsed patients after 2 courses of RCD). One patient who relapsed after 313 weeks of treatment with prednisone and other drugs cannot be treated strictly in accordance with the protocol of this study, and has not achieved CR so far after 1.5 courses of RCD within 12 weeks. The median follow-up for patients with CR was 9 weeks (range, 1
44 weeks). During RCD treatment, 1 patient expernced asymptomatic lymphocytopenia (Grade 1 AE), and another developed bacterial pneumonia (Grade 2 AE), which was rapidly controlled with antibiotics without affecting IST.
Conclusion:
This study demonstrates that the pulse RCD regimen is effective with low toxicity for AHA (including relapsing and newly diagnosed patients), which should be considered as an attractive treatment option. However, more studies and longer follow-up periods are still needed to verify the efficacy and safety of this regimen.
