Almanac of Clinical MedicineAlmanac of Clinical MedicineАльманах клинической медицины2072-05052587-9294Moscow Regional Research and Clinical Institute (MONIKI)135110.18786/2072-0505-2020-48-046REVIEW ARTICLEОБЗОРExtracorporeal photopheresis in solid organ transplantationЭкстракорпоральный фотоферез при трансплантации солидных органовhttps://orcid.org/0000-0002-7079-8383KildyushevskyA. V.КильдюшевскийА. В.
Russian Federation

Alexander V. Kildyushevsky – MD, PhD, Professor, Leading Research Fellow, Department of Clinical Hematology and Immunotherapy

61/2 Shchepkina ul., Moscow, 129110

Tel.: +7 (903) 614 86 65

Кильдюшевский Александр Вадимович – д-р мед. наук, профессор, вед. науч. сотр. отделения клинической гематологии и иммунотерапии

129110, г. Москва, ул. Щепкина, 61/2

Тел.: +7 (903) 614 86 65

kildushev@yandex.ruhttps://orcid.org/0000-0002-0002-9183MoysyukYa. G.МойсюкЯ. Г.
Russian Federation

Yan G. Moysyuk – MD, PhD, Professor, Head of Department of Transplantology

61/2 Shchepkina ul., Moscow, 129110

Мойсюк Ян Геннадиевич – д-р мед. наук, профессор, руководитель отдела трансплантологии

129110, г. Москва, ул. Щепкина, 61/2

moysyuktrans@list.ruhttps://orcid.org/0000-0002-6456-998XMolochkovA. V.МолочковА. В.
Russian Federation

Anton V. Molochkov – MD, PhD, Professor, Deputy Director

61/2 Shchepkina ul., Moscow, 129110

Молочков Антон Владимирович – д-р мед. наук, профессор, заместитель директора по науке и международным связям

129110, г. Москва, ул. Щепкина, 61/2

a.molochkov@monikiweb.ruhttps://orcid.org/0000-0001-7493-0030MitinaT. A.МитинаТ. А.
Russian Federation

Tatiana A. Mitina – MD, PhD, Head of the Department of Clinical Hematology and Immunotherapy

61/2 Shchepkina ul., Moscow, 129110

Митина Татьяна Алексеевна – д-р мед. наук, руководитель отделения клинической гематологии и иммунотерапии

129110, г. Москва, ул. Щепкина, 61/2

fmi_69@inbox.ruhttps://orcid.org/0000-0001-6158-233XFaenkoA. P.ФаенкоА. П.
Russian Federation

Alexandr P. Faenko – MD, PhD, Associate Professor, Course of Clinical Transfusiology, Chair of Anesthesiology and Intensive Care, Postgraduate Training Faculty

61/2 Shchepkina ul., Moscow, 129110

Фаенко Александр Павлович – канд. мед. наук, доцент курса клинической трансфузиологии при кафедре анестезиологии и реанимации факультета усовершенствования врачей

129110, г. Москва, ул. Щепкина, 61/2

alexfaenko@mail.ruMoscow Regional Research and Clinical Institute (MONIKI)ГБУЗ МО «Московский областной научно-исследовательский клинический институт им. М.Ф. Владимирского»051020204832072242809202028092020Copyright ©; 2020, Kildyushevsky A.V., Moysyuk Y.G., Molochkov A.V., Mitina T.A., Faenko A.P.Copyright ©; 2020, Кильдюшевский А.В., Мойсюк Я.Г., Молочков А.В., Митина Т.А., Фаенко А.П.2020Kildyushevsky A.V., Moysyuk Y.G., Molochkov A.V., Mitina T.A., Faenko A.P.Кильдюшевский А.В., Мойсюк Я.Г., Молочков А.В., Митина Т.А., Фаенко А.П.https://creativecommons.org/licenses/by/4.0https://almclinmed.ru/jour/article/view/1351

Despite the use of up-to-date immunosuppressive agents, graft rejection episodes are quite common and pose a serious threat to thousands of solid organ recipients. Continuous use of various combinations of immunosuppressants cause serious complications, such as arterial hypertension, post-transplant diabetes mellitus, renal failure, increased risk of infections, malignant neoplasms, etc. The attempts to achieve the desired or forced minimization of the graft immunosuppression are associated with the threat of its rejection, which makes it necessary to search for less toxic, non-medical, immunological, including cellular, management methods. One of the promising methods based on cell technology is extracorporeal photopheresis (ECP). ECP is a well-established second line therapy recommended for the prevention and treatment of refractory rejection of a heart transplant. ECP improves the pulmonary allograft functioning in patients with treatment resistant obliterating bronchiolitis syndrome. However, its value as a preventive method has not yet been established. ECP effectiveness for induction, maintenance, or anti-crisis therapy in transplantation of kidney, liver or other solid organs has been rather convincing, but the lack of randomized multicenter studies limits its use. The optimal ECP strategy has not been yet established. Nevertheless, current understanding of the pathophysiological and immunological aspects of ECP is sufficient to develop a standard methodology and technology for the procedure, as well as for a quality control system for ECP in kidney and liver transplant recipients. The review discusses possible mechanisms of the immunomodulating effect of ECP. ECP is being increasingly studied in prospective randomized trials with larger samples. This allows for an extension of its clinical indications with clear criteria, as well as for studying its multifactorial underlying immunomodulating mechanism of action. Further research is needed to identify biomarkers that could predict ECP effectiveness in solid organ transplantation.

Несмотря на применение современных иммуносупрессивных препаратов эпизоды отторжения трансплантата встречаются достаточно часто и представляют серьезную угрозу для тысяч реципиентов солидных органов. Длительное применение различных комбинаций иммуносупрессивных препаратов вызывает тяжелые осложнения, такие как артериальная гипертензия, посттрансплантационный сахарный диабет, почечная недостаточность, повышенный риск инфекций, злокачественных новообразований и др. При попытках желаемой или вынужденной минимизации иммуносупрессии трансплантата сохраняется угроза его отторжения, что вызывает необходимость поиска менее токсичных, немедикаментозных, иммунологических, в том числе клеточных, методов лечения. К перспективным методам, основанным на клеточных технологиях, относится экстракорпоральный фотоферез (ЭКФ), хорошо зарекомендовавший себя в качестве терапии второй линии и рекомендуемый для профилактики и лечения рефрактерного отторжения сердечного трансплантата. Применение ЭКФ позволяет улучшить функцию легочных аллотрансплантатов у пациентов с резистентностью к лечению синдрома облитерирующего бронхиолита. Однако его значение для профилактики этого синдрома пока не ясно. Эффективность ЭКФ в качестве индукционной, поддерживающей или антикризовой терапии при трансплантации почек, печени или других солидных органов достаточно убедительна, но отсутствие рандомизированных многоцентровых исследований ограничивает его применение. Оптимальная тактика проведения ЭКФ пока не установлена, тем не менее современного понимания патофизиологических и иммунологических аспектов метода достаточно для разработки стандартной методологии и технологии проведения самой процедуры, а также системы контроля качества проведения ЭКФ реципиентам трансплантата почки и печени. Авторы обзора также обсуждают возможные механизмы иммуномодулирующего действия ЭКФ.

Сегодня ЭКФ все активнее изучается в проспективных рандомизированных исследованиях с достаточно крупными выборками. Благодаря этому становится возможным расширить клинические показания метода с определением четких критериев, а также изучить лежащий в его основе сложный иммуномодулирующий механизм действия. Необходимы дальнейшие исследования по выявлению биомаркеров, которые могут быть предикторами эффективности ЭКФ при трансплантации солидных органов.

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