Arteriovenous malformations (AVMs) are fast-flow lesions that may be destructive and are the most difficult-to-treat vascular anomalies. Embolization followed by surgical resection is commonly used; however, complete resection is rarely possible and partial resection often leads to dramatic worsening. Accumulating data implicate abnormal angiogenic activity in the development of AVMs. Thalidomide has been reported as an inhibitor of vascular proliferation. Here, we report a prospective experimental observational study testing the effects of the angiogenesis inhibitor thalidomide on 18 patients with a severely symptomatic AVM that is refractory to conventional therapies. All patients experienced a rapid reduction in pain, cessation of bleeding, and ulcer healing. Cardiac failure resolved in all three affected patients. Reduced vascularity on arteriography was observed in two patients. One AVM appeared to be cured after 19 months of thalidomide and an 8-year follow-up. Eight AVMs were stable after a mean thalidomide cessation of 58 months, and four lesions recurred after 11.5 months. Combined treatment with embolization permitted dose reduction in five patients with clinical improvement. Grade 3 side effects were dose dependent, including asthenia (n = 2) and erythroderma (n = 2). The results suggest that thalidomide is efficacious in the management of chronic pain, bleeding and ulceration of extensive AVMs that are refractory to conventional therapy. Further clinical study is needed to confirm the safety and efficacy of thalidomide treatment in AVM.
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All authors but one (A.D.) are members of the VASCA Working Group of VASCERN, project no. 769036. We are grateful to all of the patients for their invaluable participation. This work is part of the thesis project of J.C., who was supported by a Fond de la Recherche Clinique (FRC) des Cliniques universitaires Saint-Luc. These studies were financially supported by Fonds de la Recherche Scientifique (FNRS) grants T.0247.19 (to M.V.) and P.C013.20 (to L.M.B.), and the Fund Generet managed by the King Baudouin Foundation (grant 2018-J1810250-211305) (to M.V.). The authors are grateful to J.B. Mulliken, P.E. Burrows and J. Dubois for their expert review of and suggestions for the manuscript; the nurse coordinator, O. Debue, for his excellent assistance in patient follow-up; and L. Niculescu and L. Huybrechts for their skilled secretarial help.
The authors declare no competing interests.
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Extended Data Fig. 1
Patient #1 with dramatic progressive aggravation of her AVM due to several partial surgical resection and embolization. (a) stage I AVM involving her upper lip at the age of 20. (b) stage IV AVM at the age of 50 now involving her entire central face and causing labial and palatal ulceration. (c) arteriography showing the extensiveness of her AVM. (D) 1 month after thalidomide initiation (d,e) showing cessation of mucosal bleeding of the lip, cessation of drooling and complete healing of her palate.
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Boon, L.M., Dekeuleneer, V., Coulie, J. et al. Case report study of thalidomide therapy in 18 patients with severe arteriovenous malformations. Nat Cardiovasc Res 1, 562–567 (2022). https://doi.org/10.1038/s44161-022-00080-2
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