uzspbgmuУчёные записки Первого Санкт-Петербургского государственного медицинского университета имени академика И. П. ПавловаThe Scientific Notes of the Pavlov University1607-41812541-8807Academician I.P. Pavlov First St. Petersburg State Medical University10.24884/1607-4181-2020-27-4-62-70uzspbgmu-773Research ArticleОРИГИНАЛЬНЫЕ РАБОТЫORIGINAL PAPERSАнализ факторов риска и эффективности Дефибротида для лечения синдрома обструкции синусоидов/веноокклюзионной болезни печени после аллогенной трансплантации гемопоэтических стволовых клеток у детей и взрослыхRisk factors analysis and defibrotide efficacy in the treatment of children and adults with sinusoidal obstructive syndrome/veno-occlusive liver disease after allogeneic hematopoietic stem cell transplantationКанунниковМ. М.KanunnikovM. M.

Канунников Михаил Михайлович = врач-гематолог, НИИДОГиТ им. Р.М. Горбачёвой.

Санкт-Петербург.

Kanunnikov Mikhail М. - Hematologist, Raisa Gorbacheva Memorial Research Institute for Pediatric Oncology, Hematology and Transplantation, Pavlov University.

Saint Petersburg.

6k6@mail.ruРахмановаЖ. З.RakhmanovaJ. Z.

Рахманова Жемал Зарифовна - врач-педиатр, НИИДОГиТ им. Р.М. Горбачёвой.

Санкт-Петербург.

Rakhmanova Jemal Z. - Pediatrician, Raisa Gorbacheva Memorial Research Institute for Pediatric Oncology, Hematology and Transplantation, Pavlov University.

Saint Petersburg.

rakhmanovazhemal@gmail.comhttps://orcid.org/0000-0002-5273-5581БарабанщиковаМ. В.BarabanshikovaM. V.

Барабанщикова Мария Владимировна - кандидат медицинских наук, старший научный сотрудник отдела детской онкологии, гематологии и трансплантологии, НИИДОГиТ им. Р.М. Горбачёвой.

Санкт-Петербург.

Barabanshikova Maria V. - Cand. of Sci. (Med.), Senior Research Fellow of the Department of Pediatric Oncology, Hematology and Transplantology, Raisa Gorbacheva Memorial Research Institute for Pediatric Oncology, Hematology and Transplantation, Pavlov University.

Saint Petersburg.

maria.barabanshikova.spb@gmail.comЛевковскийН. В.LevkovskyN. V.

Левковский Никита Вячеславович – студент.

Санкт-Петербург.

Levkovsky Nikita V. - Student, Pavlov University.

Saint Petersburg.

nik__98@mail.ruВафинаА. И.WafinaA. I.

Вафина Алия Ильсуровна – студентка.

Санкт-Петербург.

Wafina Alia I. - Student, Pavlov University.

Saint Petersburg.

aliyasnow7@gmail.comПаинаО. В.PainaO. V.

Паина Олеся Владимировна - кандидат медицинских наук, заведующая отделением трансплантации костного мозга для детей № 1 клиники, НИИДОГиТ им. Р.М. Горбачёвой.

Санкт-Петербург.

Paina Olesya V. - Cand. of Sci. (Med.), Head of the Department of Bone Marrow Transplantation for Children № 1 of the Clinic of the Raisa Gorbacheva Memorial Research Institute for Pediatric Oncology, Hematology and Transplantation, Pavlov University.

Saint Petersburg.

paina@mail.ruБыковаТ. А.BykovaT. A.

Быкова Татьяна Александровна - кандидат медицинских наук, заведующая отделением трансплантации костного мозга для детей c орфанными заболеваниями клиники НИИДОГиТ им. Р.М. Горбачёвой.

Санкт-Петербург.

Bykova Тatjana А. - Cand. of Sci. (Med.), Head of the Department of Bone Marrow Transplantation for Children with Orphan Diseases, of the Clinic of the Raisa Gorbacheva Memorial Research Institute for Pediatric Oncology, Hematology and Transplantation, Pavlov University.

Saint Petersburg.

dr.bykova@mail.ruСеменоваЕ. В.SemenovaЕ. V.

Семенова Елена Владимировна - доктор медицинских наук, профессор кафедры гематологии, трансфузиологии и трансплантологии, декан Педиатрического факультета.

Санкт-Петербург.

Semenova Еlena V. - Dr. of Sci. (Med.), Professor of the Department of Hematology, Transfusiology and Transplantology, Dean of the Faculty of Pediatrics, Pavlov University.

Saint Petersburg.

alena-semenova@yandex.ruГолощаповО. В.GoloshapovО. V.

Голощапов Олег Валерьевич - заведующий отделением реанимации и интенсивной терапии клиники НИИДОГиТ им. Р.М. Горбачёвой.

Санкт-Петербург.

Goloshapov Oleg V. - Head of the Department of Resuscitation and Intensive Care of the Clinic of the Raisa Gorbacheva Memorial Research Institute for Pediatric Oncology, Hematology and Transplantation, Pavlov University.

Saint Petersburg.

golocht@yandex.ruМорозоваЕ. В.MorozovaE. V.

Морозова Елена Владиславовна - кандидат медицинских наук, доцент кафедры гематологии, трансфузиологии и трансплантологии.

Санкт-Петербург.

Morozova Еlena V. - Cand. of Sci. (Med.), Associate Professor of the Department of Hematology, Transfusiology and Transplantology, Pavlov University.

Saint Petersburg.

dr_morozova@mail.ruМоисеевИ. С.MоiseevI. S.

Моисеев Иван Сергеевич - доктор медицинских наук, доцент, заместитель директора по научной работе, НИИДОГиТ им. Р. М. Горбачёвой.

Санкт-Петербург.

Mоiseev Ivan S. - Dr. of Sci. (Med.), Associate Professor, Deputy Director for Scientific Work, Raisa Gorbacheva Memorial Research Institute for Pediatric Oncology, Hematology and Transplantation, Pavlov University.

Saint Petersburg.

moisiv@mail.ruЗубаровскаяЛ. С.ZubarovskayaL. S.

Зубаровская Людмила Степановна - доктор медицинских наук, профессор, руководитель отдела детской онкологии, гематологии и трансплантологии, НИИДОГиТ им. Р.М. Горбачёвой.

Санкт-Петербург.

Zubarovskaya Ludmila S. - Dr. of Sci. (Med.), Professor, Head of the Department of Pediatric Oncology, Hematology and Transplantology, Raisa Gorbacheva Memorial Research Institute for Pediatric Oncology, Hematology and Transplantation, Pavlov University.

Saint Petersburg.

zubarovskaya_ls@mail.ruПервый Санкт-Петербургский государственный медицинский университет имени академика И.П. Павлова Министерства здравоохранения Российской ФедерацииРоссияPavlov UniversityRussian Federation2020261120202746270Copyright © Канунников М.М., Рахманова Ж.З., Барабанщикова М.В., Левковский Н.В., Вафина А.И., Паина О.В., Быкова Т.А., Семенова Е.В., Голощапов О.В., Морозова Е.В., Моисеев И.С., Зубаровская Л.С., 20212021Канунников М.М., Рахманова Ж.З., Барабанщикова М.В., Левковский Н.В., Вафина А.И., Паина О.В., Быкова Т.А., Семенова Е.В., Голощапов О.В., Морозова Е.В., Моисеев И.С., Зубаровская Л.С.Kanunnikov M.M., Rakhmanova J.Z., Barabanshikova M.V., Levkovsky N.V., Wafina A.I., Paina O.V., Bykova T.A., Semenova Е.V., Goloshapov О.V., Morozova E.V., Mоiseev I.S., Zubarovskaya L.S.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.sci-notes.ru/jour/article/view/773Введение

Введение. Синдром обструкции синусоидов (СОС)/веноокклюзионная болезнь печени (ВОБ) — одно из фатальных осложнений аллогенной трансплантации гемопоэтических стволовых клеток (аллоТГСК).

Целью исследования является оценка факторов риска и эффективности применения Дефибротида при СОС/ ВОБ у детей и взрослых после аллоТГСК.

Методы и материалы

Методы и материалы. В исследование включены 76 пациентов НИИДОГИТ им. Р. М. Горбачёвой после аллоТГСК, у которых в период с 2001 по 2019 г. было выявлено развитие СОС/ВОБ печени. В возрасте до 18 лет наблюдали 25 (32,9 %) пациентов, 51 (68,1 %) пациент — 18 лет и старше. Из них 17 пациентов получили Дефибротид в дозе 25 мг/кг в сутки, медиана длительности терапии составила 21 день.

Результаты

Результаты. Однолетняя общая выживаемость (ОВ) была значимо выше при достижении частичного и полного ответа на терапию — 45 %, чем при отсутствии ответа — 0 % в общей группе (р = 0,001). По результатам многофакторного анализа аллоТГСК от неродственного донора ОР 2,040 (95 % ДИ 1,112 — 3,744, р = 0,021), наличие острой реакции «трансплантат против хозяина» (оРТПХ) ОР 0,496 (95 % ДИ 0,272 — 0,903, р = 0,022), степень СОС/ВОБ ОР 2,423 (95 % ДИ 1,298 — 4,524, р = 0,005) статистически значимо влияли на 1-летнюю ОВ. При применении Дефибротида и сопроводительной терапии 1-летняя ОВ не различалась в группе взрослых и детей (n=76) и составила 53 и 54 % соответственно (Р = 0,86). В многофакторном анализе аллоТГСК от неродственного донора — ОР 8,172 (95 % ДИ 2,176 — 30,696, р = 0,002) и СОС/ВОБ 2 — 3-й степени — ОР 9,077 (95 % ДИ 2,425 — 33,978, р = 0,001) — статистически значимо влияли на 1-летнюю ОВ в педиатрической группе.

Заключение

Заключение. Обнаружение неблагоприятных факторов риска позволит сделать диагностику СОС/ВОБ более своевременной и безотлагательно начать терапию, что имеет ключевое значение для эффективного лечения данного осложнения аллоТГСК.

Introduction

Introduction. Sinusoidal obstructive syndrome (SOS)/veno-occlusive liver disease (VOD) is one of the most dangerous complication of allogeneic hematopoietic stem cell transplantation (alloHSCT).

The objective of our study was to analyze risk factors associated with SOS/VOD in children and adults after alloHSCT.

Methods and materials

Methods and materials. The study included 76 patients who were diagnosed with the development of SOS/VOD after alloHSCT performed in Raisa Gorbacheva Memorial Research Institute for Pediatric Oncology, Hematology and Transplantation between 2001 and 2019. 25 patients (32.9 %) were younger than 18 years, 51 patients (68.1 %) — 18 years and older. Among them, 17 patients were treated with defibrotide at a dose of 25 mg/kg per day, median therapy duration — 21 day.

Results

Results. One-year overall survival (OS) was significantly higher when partial and complete response to the therapy was achieved — 45 %, than when there was no response — 0 % in the general group (p = 0.001). According to the results of multivariate analysis of unrelated alloHSCT HR 2.040 (95 %CI 1.112-3.744, р = 0.021), acute GVHD HR 0.496 (95 % CI 0.272-0.903, р = 0.022), moderate/severe SOS/VOD HR 2.423 (95 % CI 1.298-4.524, p = 0.005) statistically significantly influenced the 1-year OS. Defibrotide and accompanying therapy did not significantly influence the 1-year OS in children and adults (n=76) - 53 % and 54 % (p=0.86), respectively. In a multivariate analysis. unrelated alloHSCT HR 8.172 (95 %CI 2.176-30.696, р=0.002) and moderate and severe SOS/VOD HR 9.077 (95 % CI 2.425-33.978, р=0.001) significantly influenced the 1-year OS in the pediatric group.

Conclusion

Conclusion. The understanding of risk factors of adverse prognosis in patients SOS/VOD facilitates selection of patients who will benefit the most from therapy with defibrotide. Early administration of defibrotide in the course of VOD/SOS is crucial to achieve response.

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The authors declare that there are no conflicts of interest present.