Correspondence
Bevacizumab in Hereditary Hemorrhagic Telangiectasia
N Engl J Med 2009; 360:2143-2144May 14, 2009
- Article
To the Editor:
Hereditary hemorrhagic telangiectasia (HHT) (also known as the Osler–Weber–Rendu syndrome) is an inherited vascular dysplasia whose main features are mucocutaneous telangiectasias, epistaxis, gastrointestinal bleeding, and iron-deficiency anemia.1 It is a disorder of unbalanced angiogenesis.2 Patients have elevated plasma concentrations and tissue expression of vascular endothelial growth factor (VEGF) and transforming growth factor β (TGF-β).3 TGF-β stimulates the production of VEGF, which plays a key role in angiogenesis. We report on a patient with HHT1 who had an impressive response to an anti-VEGF antibody, bevacizumab.
A 42-year-old man presented with long-standing epistaxis, hemoptysis, and a hemoglobin level of 6 g per deciliter. He had a three-generation family history of HHT. The physical examination revealed mucocutaneous telangiectasias. Screening for arteriovenous malformations disclosed two pulmonary malformations. The findings on echocardiography were consistent with an intrapulmonary shunt.
Treatment with oral iron failed to raise the hemoglobin level. The patient subsequently received 4000 mg of intravenous iron during a 6-month period, with the goal of maintaining a serum ferritin level of more than 100 ng per milliliter and a hemoglobin level of more than 12 g per deciliter (Figure 1Figure 1
Changes in Serum Ferritin and Hemoglobin Levels Associated with the Administration of Intravenous Iron and Bevacizumab in a Patient with Hereditary Hemorrhagic Telangiectasia.). After treatment with intravenous iron, he received four cycles of bevacizumab, administered every 2 weeks; the dose was 10 mg per kilogram of body weight during the first two cycles and 5 mg per kilogram for the next two cycles. The serum ferritin level increased from a mean of 33 ng per milliliter in the 6 months before the initiation of bevacizumab therapy to a mean of 315 ng per milliliter in the 9 months after the initiation of bevacizumab therapy. The patient received only 2000 mg of intravenous iron during the latter period. The second infusion of iron (in May 2008) was given before the ferritin level had been checked. In January 2009, intravenous iron was administered again, because the ferritin level had dropped to 69 ng per milliliter.The patient's epistaxis improved, with a reduction from three to four episodes daily before the initiation of bevacizumab therapy to one or two episodes per week for 12 weeks after the initiation of bevacizumab therapy. Thereafter, the number of episodes increased to one or two per day, with each episode lasting approximately 10 minutes, as compared with 30 to 45 minutes before treatment with bevacizumab. The appearance of the minimally visible telangiectasias on the patient's lips, chest, and hands did not change. The hemoglobin level remained stable, at 14 to 15 g per deciliter without red-cell transfusion.
In other cases, a patient with HHT who was receiving bevacizumab for malignant mesothelioma had a dramatic reduction in gastrointestinal bleeding from arteriovenous malformations.4 A patient with severe hepatic HHT who received six courses of bevacizumab no longer required liver transplantation and was well 6 months after completing treatment.5 The 1-year follow-up of our patient suggests that the effect of bevacizumab in HHT is not permanent and that maintenance therapy may be required.
5 ReferencesPrithviraj Bose, M.D.
Jennifer L. Holter, M.D.
George B. Selby, M.D.
University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104
prithviraj-bose@ouhsc.edu 1
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- Citing Articles (17)
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C. Rohrmeier, H. G. Sachs, T. S. Kuehnel. (2012) A retrospective analysis of low dose, intranasal injected bevacizumab (Avastin) in hereditary haemorrhagic telangiectasia. European Archives of Oto-Rhino-Laryngology 269:2, 531-536
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Georgia Lazaraki, Evangelos Akriviadis, Ioannis Pilpilidis, Ioanna Parisi, Dimitrios Tzilves, Anestis Tarpangos. (2011) Low Dose of Bevacizumab Is Safe and Effective in Preventing Bleeding Episodes in Hereditary Hemorrhagic Telangiectasia. The American Journal of Gastroenterology 106:12, 2204-2206
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Erik Storkebaum, Annelies Quaegebeur, Miikka Vikkula, Peter Carmeliet. (2011) Cerebrovascular disorders: molecular insights and therapeutic opportunities. Nature Neuroscience 14:11, 1390-1397
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Brian T. Brinkerhoff, Nicholas W. Choong, Jonathan S. Treisman, David M. Poetker. (2011) Intravenous and topical intranasal bevacizumab (Avastin) in hereditary hemorrhagic telangiectasia. American Journal of Otolaryngology
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Jamie McDonald, Pinar Bayrak-Toydemir, Reed E. Pyeritz. (2011) Hereditary hemorrhagic telangiectasia: An overview of diagnosis, management, and pathogenesis. Genetics in Medicine 13:7, 607-616
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Philip Fodstad, Sinan Dheyauldeen, Marit Rinde, Gregor Bachmann-Harildstad. (2011) Anti-VEGF with 3-week intervals is effective on anemia in a patient with severe hereditary hemorrhagic telangiectasia. Annals of Hematology 90:5, 611-612
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Sonia Chen, Tom Karnezis, Terence M. Davidson. (2011) Safety of intranasal Bevacizumab (avastin) treatment in patients with hereditary hemorrhagic telangiectasia-associated epistaxis. The Laryngoscope 121:3, 644-646
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Tom T. Karnezis, Terence M. Davidson. (2011) Efficacy of intranasal bevacizumab (Avastin) treatment in patients with hereditary hemorrhagic telangiectasia-associated epistaxis. The Laryngoscope 121:3, 636-638
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Brinkerhoff, Brian T., Poetker, David M., Choong, Nicholas W., . (2011) Long-Term Therapy with Bevacizumab in Hereditary Hemorrhagic Telangiectasia. New England Journal of Medicine 364:7, 688-689
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Claire L Shovlin, Fatima S Govani. (2010) Reply to Fernández-Fernández. European Journal of Human Genetics 18:4, 404-405
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Francisco José Fernández-Fernández. (2010) Hereditary haemorrhagic telangiectasia: From symptomatic management to pathogenesis based treatment. European Journal of Human Genetics 18:4, 404-404
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Franck Lebrin, Samly Srun, Karine Raymond, Sabrina Martin, Stieneke van den Brink, Catarina Freitas, Christiane Bréant, Thomas Mathivet, Bruno Larrivée, Jean-Léon Thomas, Helen M Arthur, Cornelis J J Westermann, Frans Disch, Johannes J Mager, Repke J Snijder, Anne Eichmann, Christine L Mummery. (2010) Thalidomide stimulates vessel maturation and reduces epistaxis in individuals with hereditary hemorrhagic telangiectasia. Nature Medicine 16:4, 420-428
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O. Blétry, T. Sene, J.-E. Kahn, F. Ackermann, P. Charles, J. Leport, A.-M. Piette. (2009) Quoi de neuf en médecine interne ?. Annales de Dermatologie et de Vénéréologie 136, S417-S425
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(2009) More on Bevacizumab in Hereditary Hemorrhagic Telangiectasia. New England Journal of Medicine 361:9, 931-932
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