.: ORİJİNAL ARAŞTIRMA
Course of Treatment of Chronic Bleeding and Anemia with Systemic Bevacizumab Treatment in Hereditary Hemorrhagic Telangiectasia: A Retrospective Cohort
Herediter Hemorajik Telenjiyektazide Sistemik Bevasizumab Tedavisiyle Kronik Kanama ve Anemi Tedavisinin Seyri: Bir Retrospektif Kohort
Turkiye Klinikleri J Med Sci. 2023;43(3):281-6
doi: 10.5336/medsci.2023-96203
Makale Dili: EN
Tam Metin
Ücretsiz Erişim
ABSTRACT
Objective: Hereditary hemorrhagic telangiectasia (HHT), is an autosomal dominant disorder that causes abnormal angiogenesis. Interest in targeted therapies has been increasing in recent years, especially for the treatment of severe forms of HHT. One of these treatment options is the vascular endothelial growth factor inhibitor bevacizumab. Purpose of this study is to investigate the effect of systemic bevacizumab use on the treatment of chronic bleeding course and anemia in patients diagnosed with HHT. Material and Methods: The treatment response and adverse events of patients with bevacizumab were evaluated retrospectively. Results: The mean age was 51,5. Mean duration of treatment was 15.4 (4-25 months) months. The first 4 doses of 5 mg/kg intravenous bevacizumab were administered at 2-week intervals in all patients. Bevacizumab maintenance continued at a dose of 5 mg/kg in monthly periods. With bevacizumab treatment, an increase in hemoglobin values, a decrease in epistaxis severity score, parenteral iron and erythrocyte transfusion requirement were achieved. Side effects observed were allergic rash in one patient and arthralgia in one patient. None of the patients required discontinuation of treatment due to side effects. Conclusion: Bevacizumab is a promising treatment option in HHT, which can be mortal if not controlled. However, there remains a need for more comprehensive studies in order to achieve a global consensus on treatment protocols and management of adverse events.
Keywords: Bevacizumab; hereditary hemorrhagic telangiectasia; epistaxis
Objective: Hereditary hemorrhagic telangiectasia (HHT), is an autosomal dominant disorder that causes abnormal angiogenesis. Interest in targeted therapies has been increasing in recent years, especially for the treatment of severe forms of HHT. One of these treatment options is the vascular endothelial growth factor inhibitor bevacizumab. Purpose of this study is to investigate the effect of systemic bevacizumab use on the treatment of chronic bleeding course and anemia in patients diagnosed with HHT. Material and Methods: The treatment response and adverse events of patients with bevacizumab were evaluated retrospectively. Results: The mean age was 51,5. Mean duration of treatment was 15.4 (4-25 months) months. The first 4 doses of 5 mg/kg intravenous bevacizumab were administered at 2-week intervals in all patients. Bevacizumab maintenance continued at a dose of 5 mg/kg in monthly periods. With bevacizumab treatment, an increase in hemoglobin values, a decrease in epistaxis severity score, parenteral iron and erythrocyte transfusion requirement were achieved. Side effects observed were allergic rash in one patient and arthralgia in one patient. None of the patients required discontinuation of treatment due to side effects. Conclusion: Bevacizumab is a promising treatment option in HHT, which can be mortal if not controlled. However, there remains a need for more comprehensive studies in order to achieve a global consensus on treatment protocols and management of adverse events.
Keywords: Bevacizumab; hereditary hemorrhagic telangiectasia; epistaxis
ÖZET
Amaç: Kalıtsal hemorajik telenjiyektazi (HHT), anormal anjiyogeneze neden olan otozomal dominant bir hastalıktır. Son yıllarda, özellikle şiddetli HHT formlarının tedavisi için hedefe yönelik tedavilere olan ilgi artmaktadır. Bu tedavi seçeneklerinden biri de vasküler endotelyal büyüme faktörü inhibitörü bevasizumabtır. Bu çalışmanın amacı, HHT tanısı alan hastalarda sistemik bevasizumab kullanımının kronik kanama seyri ve anemi tedavisindeki etkisini araştırmaktır. Gereç ve Yöntemler: Bevasizumab kullanan hastaların tedavi yanıtı ve yan etkileri retrospektif olarak değerlendirildi. Bulgular: Hastaların yaş ortalaması 51,5 yıl idi. Ortalama tedavi süresi 15,4 (4-25 ay) aydı. Tüm hastalara 2 hafta arayla ilk 4 doz 5 mg/kg intravenöz bevasizumab uygulandı. Bevasizumab idamesi 5 mg/kg dozunda aylık periyotlarla devam etti. Bevasizumab tedavisi ile hemoglobin değerlerinde artış, epistaksis şiddet skorunda parenteral demir ve eritrosit transfüzyon gereksiniminde azalma sağlandı. Gözlenen yan etkiler, 1 hastada alerjik döküntü ve 1 hastada artralji idi. Yan etkiler nedeniyle hiçbir hastada tedavinin kesilmesi gerekmedi. Sonuç: Bevasizumab, kontrol edilmediği takdirde ölümcül olabilen HHT'de umut verici bir tedavi seçeneğidir. Bununla birlikte, tedavi protokolleri ve advers olayların yönetimi konusunda global konsensus sağlamak için daha kapsamlı çalışmalara ihtiyaç vardır.
Anahtar Kelimeler: Bevasizumab; herediter hemorajik telenjiyektazi; epistaksis
Amaç: Kalıtsal hemorajik telenjiyektazi (HHT), anormal anjiyogeneze neden olan otozomal dominant bir hastalıktır. Son yıllarda, özellikle şiddetli HHT formlarının tedavisi için hedefe yönelik tedavilere olan ilgi artmaktadır. Bu tedavi seçeneklerinden biri de vasküler endotelyal büyüme faktörü inhibitörü bevasizumabtır. Bu çalışmanın amacı, HHT tanısı alan hastalarda sistemik bevasizumab kullanımının kronik kanama seyri ve anemi tedavisindeki etkisini araştırmaktır. Gereç ve Yöntemler: Bevasizumab kullanan hastaların tedavi yanıtı ve yan etkileri retrospektif olarak değerlendirildi. Bulgular: Hastaların yaş ortalaması 51,5 yıl idi. Ortalama tedavi süresi 15,4 (4-25 ay) aydı. Tüm hastalara 2 hafta arayla ilk 4 doz 5 mg/kg intravenöz bevasizumab uygulandı. Bevasizumab idamesi 5 mg/kg dozunda aylık periyotlarla devam etti. Bevasizumab tedavisi ile hemoglobin değerlerinde artış, epistaksis şiddet skorunda parenteral demir ve eritrosit transfüzyon gereksiniminde azalma sağlandı. Gözlenen yan etkiler, 1 hastada alerjik döküntü ve 1 hastada artralji idi. Yan etkiler nedeniyle hiçbir hastada tedavinin kesilmesi gerekmedi. Sonuç: Bevasizumab, kontrol edilmediği takdirde ölümcül olabilen HHT'de umut verici bir tedavi seçeneğidir. Bununla birlikte, tedavi protokolleri ve advers olayların yönetimi konusunda global konsensus sağlamak için daha kapsamlı çalışmalara ihtiyaç vardır.
Anahtar Kelimeler: Bevasizumab; herediter hemorajik telenjiyektazi; epistaksis
REFERANSLAR:
- Marchuk DA. Genetic abnormalities in hereditary hemorrhagic telangiectasia. Curr Opin Hematol. 1998;5(5):332-8. [Crossref] [PubMed]
- Westermann CJ, Rosina AF, De Vries V, de Coteau PA. The prevalence and manifestations of hereditary hemorrhagic telangiectasia in the Afro-Caribbean population of the Netherlands Antilles: a family screening. Am J Med Genet A. 2003;116A(4):324-8. [Crossref] [PubMed]
- Kritharis A, Al-Samkari H, Kuter DJ. Hereditary hemorrhagic telangiectasia: diagnosis and management from the hematologist's perspective. Haematologica. 2018;103(9):1433-43. [Crossref] [PubMed] [PMC]
- Richards-Yutz J, Grant K, Chao EC, Walther SE, Ganguly A. Update on molecular diagnosis of hereditary hemorrhagic telangiectasia. Hum Genet. 2010;128(1):61-77. [Crossref] [PubMed]
- Kühnel T, Wirsching K, Wohlgemuth W, Chavan A, Evert K, Vielsmeier V. Hereditary Hemorrhagic Telangiectasia. Otolaryngol Clin North Am. 2018;51(1):237-54. [Crossref] [PubMed]
- Brydon HL, Akinwunmi J, Selway R, Ul-Haq I. Brain abscesses associated with pulmonary arteriovenous malformations. Br J Neurosurg. 1999;13(3):265-9. [Crossref] [PubMed]
- Cho D, Kim S, Kim M, Seo YH, Kim W, Kang SH, et al. Two cases of high output heart failure caused by hereditary hemorrhagic telangiectasia. Korean Circ J. 2012;42(12):861-5. [Crossref] [PubMed] [PMC]
- Jessurun GA, Kamphuis DJ, van der Zande FH, Nossent JC. Cerebral arteriovenous malformations in The Netherlands Antilles. High prevalence of hereditary hemorrhagic telangiectasia-related single and multiple cerebral arteriovenous malformations. Clin Neurol Neurosurg. 1993;95(3):193-8. [Crossref] [PubMed]
- AAssar OS, Friedman CM, White RI Jr. The natural history of epistaxis in hereditary hemorrhagic telangiectasia. Laryngoscope. 1991;101(9):977-80. [Crossref] [PubMed]
- Shovlin CL, Guttmacher AE, Buscarini E, Faughnan ME, Hyland RH, Westermann CJ, et al. Diagnostic criteria for hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber syndrome). Am J Med Genet. 2000;91(1):66-7. [Crossref] [PubMed]
- Iyer VN, Apala DR, Pannu BS, Kotecha A, Brinjikji W, Leise MD, et al. Intravenous bevacizumab for refractory hereditary hemorrhagic telangiectasia-related epistaxis and gastrointestinal bleeding. Mayo Clin Proc. 2018;93(2):155-66. Erratum in: Mayo Clin Proc. 2018;93(3):396. [Crossref] [PubMed]
- Kjeldsen Jens, Fialla Annette D, Tine Rosenberg ADK. Bevacizumab as treatment of bleeding in patients with hereditary haemorrhagic telangiectasia (HHT). Gastroenterology. 2018;154:S701-2. [Crossref]
- Yin LX, Reh DD, Hoag JB, Mitchell SE, Mathai SC, Robinson GM, et al. The minimal important difference of the epistaxis severity score in hereditary hemorrhagic telangiectasia. Laryngoscope. 2016;126(5):1029-32. [Crossref] [PubMed]
- Lesca G, Olivieri C, Burnichon N, Pagella F, Carette MF, Gilbert-Dussardier B, et al; French-Italian-Rendu-Osler Network. Genotype-phenotype correlations in hereditary hemorrhagic telangiectasia: data from the French-Italian HHT network. Genet Med. 2007;9(1):14-22. [Crossref] [PubMed]
- Shovlin CL, Simeoni I, Downes K, Frazer ZC, Megy K, Bernabeu-Herrero ME, et al. Mutational and phenotypic characterization of hereditary hemorrhagic telangiectasia. Blood. 2020;136(17):1907-18. [Crossref] [PubMed] [PMC]
- Jelsig AM, Kjeldsen A, Christensen LL, Bertelsen B, Karstensen JG, Brusgaard K, et al. Hereditary haemorrhagic telangiectasia in Danish patients with pathogenic variants in SMAD4: a nationwide study. J Med Genet. 2023;60(5):464-8. [Crossref] [PubMed]
- Guilhem A, Fargeton AE, Simon AC, Duffau P, Harle JR, Lavigne C, et al. Intra-venous bevacizumab in hereditary hemorrhagic telangiectasia (HHT): a retrospective study of 46 patients. PLoS One. 2017;12(11):e0188943. [Crossref] [PubMed] [PMC]
- Gaillard S, Dupuis-Girod S, Boutitie F, Rivière S, Morinière S, Hatron PY, et al; ATERO Study Group. Tranexamic acid for epistaxis in hereditary hemorrhagic telangiectasia patients: a European cross-over controlled trial in a rare disease. J Thromb Haemost. 2014;12(9):1494-502. [Crossref] [PubMed]
- Vase P. Estrogen treatment of hereditary hemorrhagic telangiectasia. A double-blind controlled clinical trial. Acta Med Scand. 1981;209(5):393-6. [Crossref] [PubMed]
- Whitehead KJ, Sautter NB, McWilliams JP, Chakinala MM, Merlo CA, Johnson MH, et al. Effect of topical intranasal therapy on epistaxis frequency in patients with hereditary hemorrhagic telangiectasia: a randomized clinical trial. JAMA. 2016;316(9):943-51. [Crossref] [PubMed]
- Dupuis-Girod S, Pitiot V, Bergerot C, Fargeton AE, Beaudoin M, Decullier E, et al. Efficacy of TIMOLOL nasal spray as a treatment for epistaxis in hereditary hemorrhagic telangiectasia. A double-blind, randomized, placebo-controlled trial. Sci Rep. 2019;9(1):11986. [Crossref] [PubMed] [PMC]
- Cirulli A, Liso A, D'Ovidio F, Mestice A, Pasculli G, Gallitelli M, et al. Vascular endothelial growth factor serum levels are elevated in patients with hereditary hemorrhagic telangiectasia. Acta Haematol. 2003;110(1):29-32. [Crossref] [PubMed]
- Michels S, Rosenfeld PJ, Puliafito CA, Marcus EN, Venkatraman AS. Systemic bevacizumab (Avastin) therapy for neovascular age-related macular degeneration twelve-week results of an uncontrolled open-label clinical study. Ophthalmology. 2005;112(6):1035-47. [Crossref] [PubMed]
- Bose P, Holter JL, Selby GB. Bevacizumab in hereditary hemorrhagic telangiectasia. N Engl J Med. 2009;360(20):2143-4. [Crossref] [PubMed]
- Dupuis-Girod S, Ambrun A, Decullier E, Fargeton AE, Roux A, Bréant V, et al. Effect of bevacizumab nasal spray on epistaxis duration in hereditary hemorrhagic telangectasia: a randomized clinical trial. JAMA. 2016;316(9):934-42. [Crossref] [PubMed]
- Al-Samkari H, Kasthuri RS, Parambil JG, Albitar HA, Almodallal YA, Vázquez C, et al. An international, multicenter study of intravenous bevacizumab for bleeding in hereditary hemorrhagic telangiectasia: the InHIBIT-Bleed study. Haematologica. 2021;106(8):2161-9. [Crossref] [PubMed] [PMC]
.: İşlem Listesi