Pediatric Hematology/Oncology and ImmunopathologyPediatric Hematology/Oncology and ImmunopathologyВопросы гематологии/онкологии и иммунопатологии в педиатрии1726-17082414-9314Fund Doctors, Innovations, Science for Children59810.24287/1726-1708-2022-21-1-122-135CLINICAL OBSERVATIONSКЛИНИЧЕСКИЕ НАБЛЮДЕНИЯNew approaches for solving the old problemНовые подходы к решению старой проблемыhttps://orcid.org/0000-0001-7265-0414KhachatryanL. A.ХачатрянЛ. А.
Russian Federation

Lili A. Khachatryan, Cand. Med. Sci., Head of Box Department of Hematology/Oncology

1 Samory Mashela St., Moscow 117997 

Хачатрян Лили Альбертовна, канд. мед. наук, заведующая боксированным отделением гематологии/онкологии 

117997, Москва, ул. Саморы Машела, 1

lili.2510@yandex.ruShcherbakovА. P.ЩербаковА. П.
Russian Federation

Moscow

Москва

ChikvinaI. I.ЧиквинаИ. И.
Russian Federation

Moscow

Москва

NikolaevaD. M.НиколаеваД. М.
Russian Federation

Moscow

Москва

Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian FederationФГБУ «Национальный медицинский исследовательский центр детской гематологии, онкологии и иммунологии им. Дмитрия Рогачева» Минздрава России300320222111221352903202229032022Copyright ©; 2022, «D. Rogachev NMRCPHOI»Copyright ©; 2022, ФГБУ «НМИЦ ДГОИ им. Дмитрия Рогачева» Минздрава России2022«D. Rogachev NMRCPHOI»ФГБУ «НМИЦ ДГОИ им. Дмитрия Рогачева» Минздрава Россииhttps://creativecommons.org/licenses/by/4.0https://hemoncim.com/jour/article/view/598

Infantile hemangioma (IH) is a benign vascular tumor with abnormal proliferation of endothelial cells and impaired vascular architecture. It is believed that the pathogenesis of IH is based on angiogenesis impairment caused by imbalance between angiogenic and anti-angiogenic factors. Despite spontaneous regression, which is observed in 90% of cases of IH, several tumor localizations may indicate the possibility of systemic manifestations or lead to the development of complications that require medical interventions. Here we report 2 cases of the most frequent and severe complications of IH and the first successful use of combined treatment strategy including metronomic chemotherapy (cyclophosphamide plus vinblastine) and nonselective b-blocker (propranolol) in IH. The parents of the patients agreed to use the information, including the photographs of children, in scientific research and publications. In contrast to glucocorticoids commonly used in clinical practice for complicated forms of IH, metronomic chemotherapy showed high efficacy and safety. It led to a rapid, within the first two weeks, clinical improvement resulting not only in stopping tumor growth, but even in size reduction. Such a rapid response to therapy allowed to stop the development of ulcers and necrosis with secondary infection, and to prevent severe vital complications of IH such as the upper respiratory tract compression.

Инфантильная гемангиома (ИГ) – доброкачественная сосудистая опухоль, развивающаяся в результате аномальной пролиферации эндотелиальных клеток с нарушенной архитектоникой кровеносных сосудов. Считается, что формирование ИГ обусловлено дисбалансом между ангиогенными и антиангиогенными факторами. Несмотря на спонтанный регресс, наблюдающийся в 90% случаев ИГ, некоторые виды локализаций могут указывать на возможность системных проявлений либо приводить к развитию осложнений и требовать медицинского вмешательства. В данной статье представлено 2 клинических примера наиболее частых и грозных осложнений, встречаемых при ИГ. Родители пациентов дали согласие на использование информации, в том числе фотографий детей, в научных исследованиях и публикациях. Впервые при осложненных формах ИГ было применено комбинированное лечение, включающее химиотерапию в метрономном режиме (циклофосфан + винбластин) в сочетании с неселективным b-блокатором пропранололом. В отличие от распространенного в клинической практике назначения глюкокортикостероидов при осложненных формах ИГ, метрономная химиотерапия показала свою высокую эффективность и безопасность. Она привела к быстрому (в течение первых 2 нед) достижению клинического улучшения в виде не только прекращения роста образования, но и сокращения его размеров. Столь быстрый ответ на терапию позволил купировать самые часто встречаемые локальные осложнения ИГ, такие как развитие язв/некрозов со вторичным инфицированием, а также избежать более грозного витального осложнения – сдавления верхних дыхательных путей.

infantile hemangiomapropranololmetronomic chemotherapyинфантильная гемангиомапропранололметрономная химиотерапия1. Léauté-Labrèze C., Haper J.I., Hoeger P.H. Infantile haemangioma. Lancet 2017; 390 (10089): 85–94.Léauté-Labrèze C., Haper J.I., Hoeger P.H. Infantile haemangioma. Lancet 2017; 390 (10089): 85–94.2. Wassef M., Vanwijk R., Clapuyt P., Boon L., Magalon G. Tumeurs et malformations vasculaires, classification anatomopathologique et imagerie. Ann Chir Plast Esthet 2006; 51 (4–5): 263–81Wassef M., Vanwijk R., Clapuyt P., Boon L., Magalon G. Tumeurs et malformations vasculaires, classification anatomopathologique et imagerie. Ann Chir Plast Esthet 2006; 51 (4–5): 263–813. Drolet B.A., Frommelt P.C., Chamlin S.L., Haggstrom A., Bauman N.M., Chiu Y.E., et al. Initiation and use of propranolol for infantile hemangioma: report of a consensus conference. Pediatrics 2013; 131 (1): 128–40.Drolet B.A., Frommelt P.C., Chamlin S.L., Haggstrom A., Bauman N.M., Chiu Y.E., et al. Initiation and use of propranolol for infantile hemangioma: report of a consensus conference. Pediatrics 2013; 131 (1): 128–40.4. Léauté-Labrèze C., Sans-Martin V. Hemangiome infatile. Presse Mеd 2010; 39 (4): 499–510.Léauté-Labrèze C., Sans-Martin V. Hemangiome infatile. Presse Mеd 2010; 39 (4): 499–510.5. Darrow D.H., Greene A.K., Mancini A.J., Nopper A.J., Section on Dermatology, Section on Otolaryngology–Head and Neck Surgery, and Section on Plastic Surgery. Diagnosis and management of infantile hemangioma. Pedatrics 2015; 136 (4): e1060–104Darrow D.H., Greene A.K., Mancini A.J., Nopper A.J., Section on Dermatology, Section on Otolaryngology–Head and Neck Surgery, and Section on Plastic Surgery. Diagnosis and management of infantile hemangioma. Pedatrics 2015; 136 (4): e1060–1046. Хачатрян Л.А., Клецкая И.С. Просто о сложном: инфантильная гемангиома. Вопросы гематологии/онкологии и иммунопатологии в педиатрии 2021; 20 (1): 192–206. DOI: 10.24287/1726-1708-2021-20-1-192-206Хачатрян Л.А., Клецкая И.С. Просто о сложном: инфантильная гемангиома. Вопросы гематологии/онкологии и иммунопатологии в педиатрии 2021; 20 (1): 192–206. DOI: 10.24287/1726-1708-2021-20-1-192-2067. Wechsler J. Pathologie cutanée tumoral. 2nd edition. 2016. Рр. 278–279.Wechsler J. Pathologie cutanée tumoral. 2nd edition. 2016. Рр. 278–279.8. Léauté-Labrèze C., Taïeb A. Efficacy of beta-blockers in infantile capillary haemangiomas: the physiopathological significance and therapeutic consequences. Ann Dermatol Vénéréologie 2008; 135 (12): 860–2.Léauté-Labrèze C., Taïeb A. Efficacy of beta-blockers in infantile capillary haemangiomas: the physiopathological significance and therapeutic consequences. Ann Dermatol Vénéréologie 2008; 135 (12): 860–2.9. Casanova D., Norat F., Bardot J, Magalon G. Les hémangiomes cutanés: aspects cliniques. Ann Chir Plast Esthet 2006; 51: 287–92.Casanova D., Norat F., Bardot J, Magalon G. Les hémangiomes cutanés: aspects cliniques. Ann Chir Plast Esthet 2006; 51: 287–92.10. Nakayama H. Clinical and histological studies of the classification and the natural course of the strawberry mark. J Dermatol 1981; 8 (4): 277–91.Nakayama H. Clinical and histological studies of the classification and the natural course of the strawberry mark. J Dermatol 1981; 8 (4): 277–91.11. Haggstrom A.N., Drolet B.A., Baselga E., Chamlin S.L., Garzon M.C., Horii K.A., et al. Prospective study of infantile hemangiomas: clinical characteristics predicting complications and treatment. Pediatrics 2006; 118 (3): 882–7.Haggstrom A.N., Drolet B.A., Baselga E., Chamlin S.L., Garzon M.C., Horii K.A., et al. Prospective study of infantile hemangiomas: clinical characteristics predicting complications and treatment. Pediatrics 2006; 118 (3): 882–7.12. Warner M., North P.E., Scherer K.A., Frieden I.J., Warner A., Mihm M.C. The nonrandom distribution of facial hemangiomas. Arch Dermatol 2003; 139 (7): 869–75.Warner M., North P.E., Scherer K.A., Frieden I.J., Warner A., Mihm M.C. The nonrandom distribution of facial hemangiomas. Arch Dermatol 2003; 139 (7): 869–75.13. Léauté-Labrèze С., Prey S., Ezzedine K. Infantile hemangioma: Part I. Pathophysiology, epidemiology, clinical features, life cycle and associated structural abnormalities. J Eur Acad Dermatol Venerol 2011; 25 (11): 1245–53.Léauté-Labrèze С., Prey S., Ezzedine K. Infantile hemangioma: Part I. Pathophysiology, epidemiology, clinical features, life cycle and associated structural abnormalities. J Eur Acad Dermatol Venerol 2011; 25 (11): 1245–53.14. Chang L.C., Haggstrom A.N., Drolet B.A., Baselga E., Chamlin S.L., Garzon M.C., et al. Growth characteristics of infantile hemangiomas: implications for management. Pediatrics 2008; 122 (2): 360– 7.Chang L.C., Haggstrom A.N., Drolet B.A., Baselga E., Chamlin S.L., Garzon M.C., et al. Growth characteristics of infantile hemangiomas: implications for management. Pediatrics 2008; 122 (2): 360– 7.15. Chiller K.G., Passaro D., Friden I.J. Hemangiomas of infancy: clinical characteristics, morphologic subtypes, and their relationship to race, ethnicity, and sex. Arch Dermatol 2002; 138 (12): 1567–76.Chiller K.G., Passaro D., Friden I.J. Hemangiomas of infancy: clinical characteristics, morphologic subtypes, and their relationship to race, ethnicity, and sex. Arch Dermatol 2002; 138 (12): 1567–76.16. Chamlin S.L., Haggstrom A.N., Drolet B.A., Baselga E., Frieden I.J., Garzon M.C., et al. Multicenter prospective study of ulcerated hemangiomas. J Pediatr 2007; 151 (6): 684–9.Chamlin S.L., Haggstrom A.N., Drolet B.A., Baselga E., Frieden I.J., Garzon M.C., et al. Multicenter prospective study of ulcerated hemangiomas. J Pediatr 2007; 151 (6): 684–9.17. Krowchuk D.P., Frieden I.J., Mancini A.J., Darrow D.H., Blei F., Greene A.K., et al. Clinincal Practice Guideline for the Management of Infantile Hemangiomas. Pediatrics 2019; 143 (1): e20183475.Krowchuk D.P., Frieden I.J., Mancini A.J., Darrow D.H., Blei F., Greene A.K., et al. Clinincal Practice Guideline for the Management of Infantile Hemangiomas. Pediatrics 2019; 143 (1): e20183475.18. Dubois J., Milot J., Jaeger B.I., Cuaig C.M., Rousseau E., Powell J. Orbit and eyelid hemangiomas: is there a relantionschip between location and ocular problems? J Am Acad Dermatol 2006; 55 (4): 614–9.Dubois J., Milot J., Jaeger B.I., Cuaig C.M., Rousseau E., Powell J. Orbit and eyelid hemangiomas: is there a relantionschip between location and ocular problems? J Am Acad Dermatol 2006; 55 (4): 614–9.19. Holland K.E., Drolet B.A. Infantile Hemangioma. Pediatric Clinics of North America. Pediatr Clin North Am 2010; 57 (5): 1069–83.Holland K.E., Drolet B.A. Infantile Hemangioma. Pediatric Clinics of North America. Pediatr Clin North Am 2010; 57 (5): 1069–83.20. Rahbar R., Nicollas R., Roger G., Triglia J.-M., Garabedian E.-N., McGill T.J., et al. The biology and management of subglottic hemangioma: past, present, future. Laryngoscope 2004; 114 (11): 1880–91.Rahbar R., Nicollas R., Roger G., Triglia J.-M., Garabedian E.-N., McGill T.J., et al. The biology and management of subglottic hemangioma: past, present, future. Laryngoscope 2004; 114 (11): 1880–91.21. Badi A.N., Kerschner J.E., North P.E., Drolet B.A., Messner A., Perkins J.A. Histopathologic and immunophenotypic profile of subglottic hemangioma: multicenter study. Int J Pediatr Otorhinolaryngol 2009; 73 (9): 1187–91.Badi A.N., Kerschner J.E., North P.E., Drolet B.A., Messner A., Perkins J.A. Histopathologic and immunophenotypic profile of subglottic hemangioma: multicenter study. Int J Pediatr Otorhinolaryngol 2009; 73 (9): 1187–91.22. Christison-Lagay E.R., Burrows P.E., Alomari A., Dubois J., Kozakewich H.P., Lane T.S., et al. Hepatic hemangiomas: subtype classification and development of a clinical practice algorithm and registry. J Pediatr Surg 2007; 42 (1): 62–8.Christison-Lagay E.R., Burrows P.E., Alomari A., Dubois J., Kozakewich H.P., Lane T.S., et al. Hepatic hemangiomas: subtype classification and development of a clinical practice algorithm and registry. J Pediatr Surg 2007; 42 (1): 62–8.23. Levy A.D., Abbott R.M., Rohrmann C.A., Frazier A.A., Kende A. Gastrointestinal hemangiomas: imaging finding with pathologic correlation in pediatric and adult patients. AJR Am J Roentgenol 2001; 177 (5): 1073–81.Levy A.D., Abbott R.M., Rohrmann C.A., Frazier A.A., Kende A. Gastrointestinal hemangiomas: imaging finding with pathologic correlation in pediatric and adult patients. AJR Am J Roentgenol 2001; 177 (5): 1073–81.24. Frieden I.J., Haggstrom A.N., Drolet B.A., Mancini A.J., Friedlander S.F., Boon L., et al. Infantile hemangiomas: current knowledge, future directions. Proceedings of a research workshop on infantile hemangiomas, April 7–9, 2005, Bethesda, Maryland, USA. Pediatr Dermatol 2005; 22 (5): 383–406.Frieden I.J., Haggstrom A.N., Drolet B.A., Mancini A.J., Friedlander S.F., Boon L., et al. Infantile hemangiomas: current knowledge, future directions. Proceedings of a research workshop on infantile hemangiomas, April 7–9, 2005, Bethesda, Maryland, USA. Pediatr Dermatol 2005; 22 (5): 383–406.25. Kulungowski A.M., Alomari A.I., Chawla A., Christison-Lagay E.R., Fishman S.J. Lessons from a liver hemangioma registry: subtype classification. J Pediatr Surg 2012; 47: 165–70.Kulungowski A.M., Alomari A.I., Chawla A., Christison-Lagay E.R., Fishman S.J. Lessons from a liver hemangioma registry: subtype classification. J Pediatr Surg 2012; 47: 165–70.26. Huang S.A., Tu H.M., Harney J.W., Venihaki M., Butte A.J., Kozakewich H.P., et al. Severe hypothyroidism caused by type 3 iodothyronine deiodinase in infantile hemangiomas. N Engl J Med 2000; 343 (3): 185–9.Huang S.A., Tu H.M., Harney J.W., Venihaki M., Butte A.J., Kozakewich H.P., et al. Severe hypothyroidism caused by type 3 iodothyronine deiodinase in infantile hemangiomas. N Engl J Med 2000; 343 (3): 185–9.27. Konrad D., Ellis G., Perlman K. Spontaneous Regression of Severe Acquired Infantile Hypothyroidism Associated with Multiple Liver Hemangiomas. Pediatrics 2003; 112 (6 Pt 1): 1424–6.Konrad D., Ellis G., Perlman K. Spontaneous Regression of Severe Acquired Infantile Hypothyroidism Associated with Multiple Liver Hemangiomas. Pediatrics 2003; 112 (6 Pt 1): 1424–6.28. Hoeger P.H., Harper J.I., Baselga E., Bonnet D., Boon L.M., Atti M.C.D., et al. Treatment of infantile haemangiomas: recommendations of a European expert group. Eur J Pediatr 2015; 174 (7): 855– 65.Hoeger P.H., Harper J.I., Baselga E., Bonnet D., Boon L.M., Atti M.C.D., et al. Treatment of infantile haemangiomas: recommendations of a European expert group. Eur J Pediatr 2015; 174 (7): 855– 65.29. Fuchsmann C., Quintal M.-C., Giguere C., Ayari-Khalfallah S., Guibaud L., Powell J., et al. Propranolol as first-line treatment of head and neck hemangiomas. Arch Otoloryngol Head Neck Surg 2011; 137 (5): 471–8.Fuchsmann C., Quintal M.-C., Giguere C., Ayari-Khalfallah S., Guibaud L., Powell J., et al. Propranolol as first-line treatment of head and neck hemangiomas. Arch Otoloryngol Head Neck Surg 2011; 137 (5): 471–8.30. Peschechodova E. Prise en charge de l´hémangiome infantile. These pour le diplome d´état de docteur en pharmacie. 2015. Р. 19.Peschechodova E. Prise en charge de l´hémangiome infantile. These pour le diplome d´état de docteur en pharmacie. 2015. Р. 19.31. Delmontte N., Curti C., Motana M., Crozet M., Vanelle P., Gensollen S. Mise au point sur traitement de l' hémangiome du nourrisson par beta-bloquant. Therapies 2012; 67 (3): 257–65.Delmontte N., Curti C., Motana M., Crozet M., Vanelle P., Gensollen S. Mise au point sur traitement de l' hémangiome du nourrisson par beta-bloquant. Therapies 2012; 67 (3): 257–65.32. Folkman J., Mulliken J.B., Ezekowitz R.A.B. Antiangiogenic therapy of haemangiomas with interferon A. The clinical applications of the interferons. London, England: Chapman Hall Medical; 1997. Рр. 255–265.Folkman J., Mulliken J.B., Ezekowitz R.A.B. Antiangiogenic therapy of haemangiomas with interferon A. The clinical applications of the interferons. London, England: Chapman Hall Medical; 1997. Рр. 255–265.33. Enjolras O., Brevière G., Roger G., Tovi M., Pellegrino B., Varotti E., et al. Traitement par vincristine des hémangiomes graves du nourrisson. Arch Pediatr 2004; 11 (2): 99–107.Enjolras O., Brevière G., Roger G., Tovi M., Pellegrino B., Varotti E., et al. Traitement par vincristine des hémangiomes graves du nourrisson. Arch Pediatr 2004; 11 (2): 99–107.