nodgoРоссийский журнал детской гематологии и онкологии (РЖДГиО)Russian Journal of Pediatric Hematology and Oncology2311-12672413-5496LTD “Graphica”10.21682/2311-1267-2023-10-3-55-62nodgo-963Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL STUDIESТоксические осложнения высоких доз треосульфана у детей: опыт ФГБУ «НМИЦ онкологии им. Н.Н. Блохина» Минздрава РоссииToxic complications of high doses of treîsulfan in children: experience of the N.N. Blokhin National Medical Research Centre of Oncology, Ministry of Health of Russiahttps://orcid.org/0000-0003-1091-1521АлиевТ. З.AlievT. Z.

врач-детский онколог отделения детской трансплантации костного мозга и гемопоэтических стволовых клеток

115522, Москва, Каширское шоссе, 23

Pediatric Oncologist Department of Pediatric Bone Marrow and Hematopoietic Stem Cell Transplantation

23 Kashirskoe Shosse, Moscow, 115522

timaliev118@gmail.comhttps://orcid.org/0000-0003-2395-4045МачневаЕ. Б.MachnevaE. B.

к.м.н., врач-гематолог отделения детской трансплантации костного мозга и гемопоэтических стволовых клеток

115522, Москва, Каширское шоссе, 23

119572, Москва, Ленинский просп., 117

Cand. of Sci. (Med.), Hematologist Department of Pediatric Bone Marrow and Hematopoietic Stem Cell Transplantation of the Research Institute of Pediatric Oncology and Hematology named after Academician of the Russian Academy of Medical Sciences L.A. Durnov at N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia, Hematologist Department of Bone Marrow Transplantation at the Russian Children’s Clinical Hospital – Branch of the N.I. Pirogov Russian National Research Medical University, Ministry of Health of Russia

23 Kashirskoe Shosse, Moscow, 115522

117 Leninskiy Prosp., Moscow, 117997

lena.machneva@yandex.ruhttps://orcid.org/0000-0003-0179-2479КостареваИ. О.KostarevaI. O.

врач-детский онколог отделения детской трансплантации костного мозга и гемопоэтических стволовых клеток

115522, Москва, Каширское шоссе, 23

Pediatric Oncologist Department of Pediatric Bone Marrow and Hematopoietic Stem Cell Transplantation of the Research Institute of Pediatric Oncology and Hematology named after Academician of the Russian Academy of Medical Sciences L.A. Durnov

23 Kashirskoe Shosse, Moscow, 115522

kostareva_92@mail.ruhttps://orcid.org/0000-0003-3225-8412СергеенкоК. А.SergeenkoK. A.

врач-детский онколог отделения детской трансплантации костного мозга и гемопоэтических стволовых клеток

115522, Москва, Каширское шоссе, 23

Pediatric Oncologist Department of Pediatric Bone Marrow and Hematopoietic Stem Cell Transplantation of the Research Institute of Pediatric Oncology and Hematology named after Academician of the Russian Academy of Medical Sciences L.A. Durnov

23 Kashirskoe Shosse, Moscow, 115522

karina_s19@mail.ruhttps://orcid.org/0000-0002-3289-223XБурлакаН. А.BurlakaN. A.

врач-детский онколог отделения детской трансплантации костного мозга и гемопоэтических стволовых клеток

115522, Москва, Каширское шоссе, 23

Pediatric Oncologist Department of Pediatric Bone Marrow and Hematopoietic Stem Cell Transplantation of the Research Institute of Pediatric Oncology and Hematology named after Academician of the Russian Academy of Medical Sciences L.A. Durnov

23 Kashirskoe Shosse, Moscow, 115522

dreamfull2009@yandex.ruhttps://orcid.org/0000-0002-8110-9811КудаеваЛ. М.KudaevaL. M.

студент лечебного факультета

127006, Москва, ул. Долгоруковская, 4

Student of the Faculty of Medicine

4 Dolgorukovskaya St., Moscow,127006

lkudaeva@mail.ruhttps://orcid.org/0009-0007-0074-7197ПотёмкинаТ. И.PotemkinaT. I.

врач-гематолог отделения детской трансплантации костного мозга и гемопоэтических стволовых клеток

115522, Москва, Каширское шоссе, 23

Hematologist Department of Pediatric Bone Marrow and Hematopoietic Stem Cell Transplantation of the Research Institute of Pediatric Oncology and Hematology named after Academician of the Russian Academy of Medical Sciences L.A. Durnov

23 Kashirskoe Shosse, Moscow, 115522

TanyaBukharova0802@yandex.ruhttps://orcid.org/0000-0003-0600-8962ЛозованЮ. В.LozovanYu. V.

врач-педиатр отделения детской трансплантации костного мозга и гемопоэтических стволовых клеток НИИ детской онкологии и гематологии им. акад. РАМН Л.А. Дурнова

115522, Москва, Каширское шоссе, 23

Pediatrician Department of Pediatric Bone Marrow and Hematopoietic Stem Cell Transplantation of the Research Institute of Pediatric Oncology and Hematology named after Academician of the Russian Academy of Medical Sciences L.A. Durnov

23 Kashirskoe Shosse, Moscow, 115522

lyuriimd@mail.ruhttps://orcid.org/0009-0007-2171-1951СмирноваД. С.SmirnovaD. S.

врач-детский онколог отделения детской трансплантации костного мозга и гемопоэтических стволовых клеток

115522, Москва, Каширское шоссе, 23

Pediatric Oncologist Department of Pediatric Bone Marrow and Hematopoietic Stem Cell Transplantation of the Research Institute of Pediatric Oncology and Hematology named after Academician of the Russian Academy of Medical Sciences L.A. Durnov

23 Kashirskoe Shosse, Moscow, 115522

stratostat55@gmail.comhttps://orcid.org/0000-0002-2021-0465СлининА. С.SlininA. S.

научный сотрудник отдела исследований острой лимфобластной лейкемии

117997, Москва, ул. Саморы Машела, 1

Researcher Department of Acute Lymphoblastic Leukemia Research

1 Samory Mashela St., Moscow, 117997

eukariot03@gmail.comhttps://orcid.org/0000-0002-2945-284XКиргизовК. И.KirgizovK. I.

к.м.н., заместитель директора по научной работе; заведующий отделением детской трансплантации костного мозга и гемопоэтических стволовых клеток

115522, Москва, Каширское шоссе, 23

: Cand. of Sci. (Med.), Deputy Director for Scientific Work of Research Institute of Pediatric Oncology and Hematology named after Academicianof the Russian Academy of Medical Sciences L.A. Durnov, Head of the Department of Pediatric Bone Marrow and Hematopoietic Stem Cell Transplantation of the Research Institute of Pediatric Oncology and Hematology named after Academician of the Russian Academy of Medical Sciences L.A. Durnov

23 Kashirskoe Shosse, Moscow, 115522

k.kirgizov@ronc.ruhttps://orcid.org/0000-0001-6131-1783ВарфоломееваС. Р.VarfolomeevaS. R.

д.м.н., профессор, директор

115522, Москва, Каширское шоссе, 23

Dr. of Sci. (Med.), Professor, Director of the Research Institute of Pediatric Oncology and Hematology named after Academician of the Russian Academy of Medical Sciences L.A. Durnov 

23 Kashirskoe Shosse, Moscow, 115522

s.varfolomeeva@ronc.ruФГБУ «НМИЦ онкологии им. Н.Н. Блохина» Минздрава РоссииРоссияN.N. Blokhin National Medical Research Centre of Oncology, Ministry of Health of RussiaRussian FederationФГБУ «НМИЦ онкологии им. Н.Н. Блохина» Минздрава России; РДКБ – филиал ФГАОУ ВО РНИМУ им. Н.И. Пирогова Минздрава РоссииРоссияN.N. Blokhin National Medical Research Centre of Oncology, Ministry of Health of Russia; Russian Children’s Clinical Hospital – Branch of the N.I. Pirogov Russian National Research Medical University, Ministry of Health of RussiaRussian FederationФГБОУ ВО «Московский государственный медико-стоматологический университет имени А.И. Евдокимова» Минздрава РоссиРоссияA.I. Yevdokimov Moscow State University of Medicine and Dentistry, Ministry of Health of RussiaRussian FederationФГБУ «НМИЦ ДГОИ им. Дмитрия Рогачева» Минздрава РоссииРоссияDmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Ministry of Health of RussiaRussian Federation2023301120231035562Copyright © Алиев Т.З., Мачнева Е.Б., Костарева И.О., Сергеенко К.А., Бурлака Н.А., Кудаева Л.М., Потёмкина Т.И., Лозован Ю.В., Смирнова Д.С., Слинин А.С., Киргизов К.И., Варфоломеева С.Р., 20232023Алиев Т.З., Мачнева Е.Б., Костарева И.О., Сергеенко К.А., Бурлака Н.А., Кудаева Л.М., Потёмкина Т.И., Лозован Ю.В., Смирнова Д.С., Слинин А.С., Киргизов К.И., Варфоломеева С.Р.Aliev T.Z., Machneva E.B., Kostareva I.O., Sergeenko K.A., Burlaka N.A., Kudaeva L.M., Potemkina T.I., Lozovan Y.V., Smirnova D.S., Slinin A.S., Kirgizov K.I., Varfolomeeva S.R.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://journal.nodgo.org/jour/article/view/963

Трансплантация гемопоэтических стволовых клеток (ТГСК) является методом терапии ряда тяжелых злокачественных и неопухолевых заболеваний. Аутологичная (ауто) и аллогенная (алло) ТГСК улучшают исходы у пациентов со злокачественными новообразованиями солидной и гематологической природы. Токсичность режимов кондиционирования перед ТГСК нередко является лимитирующим фактором для успешных исходов трансплантации. Наиболее частыми проявлениями висцеральной и тканевой токсичности являются эпителиальная (дерматологическая и мукозальная) токсичность, гепатотоксичность и нейротоксичность. Снижением частоты развития токсических осложнений препаративных режимов, предшествующих ТГСК, являются оптимизация сопроводительной терапии и индивидуализированный подбор доз химиопрепаратов. В нашем исследовании среди выполненных в 2021–2022 гг. ТГСК в 119 случаях использовались треосульфан-содержащие препаративные режимы. Дерматологическая токсичность диагностирована в 80,0 %, мукозит – в 100 %, гепатотоксичность – в 18,5 % наблюдений, неврологической токсичности зарегистрировано не было.

Hematopoietic stem cell transplantation (HSCT) is a treatment method for a number of severe malignant and non-tumor diseases. Autologous (auto) and allogeneic (allo) HSCT improves outcomes in patients with solid and hematological malignancies. The toxicity of conditioning regimens before HSCT is often a limiting factor for successful transplant outcomes. The most common manifestations of visceral and tissue toxicity are epithelial (dermatological and mucosal) toxicity, hepatotoxicity, and neurotoxicity. Reducing the incidence of toxic complications of preparative regimens preceding HSCT is the optimization of accompanying therapy, and and individualized selection of doses of chemotherapy. In our study, among 119 HSCT cases performed in 2021–2022, treosulfan-containing preparative regimens were used. Dermatological toxicity was diagnosed in 80.0 %, mucositis – in 100 %, hepatotoxicity – in 18.5 % of observations, no neurological toxicity was recorded.

высокодозная химиотерапиядетикожамукозитосложнениятрансплантация гемопоэтических стволовых клетоктоксичностьтреосульфанhigh-dose chemotherapychildrenskinmucositiscomplicationshematopoietic stem cell transplantationtoxicitytreosulfanReferencesАлиев Т.З., Мачнева Е.Б., Сидорова Н.В., Белышева Т.С., Валиев Т.Т., Киргизов К.И. Поражение кожных покровов при трансплантации гемопоэтических стволовых клеток. Обзор литературы. Вопросы гематологии/онкологии и иммунопатологии в педиатрии. 2020;19(2):184–92. doi: 10.24287/1726-1708-2020-19-2- 184-192.Aliev T.Z., Machneva E.B., Sidorova N.V., Belysheva T.S., Valiev T.T., Kirgizov K.I. Skin damage after the hematopoietic stem cell transplantation. Literature review. Voprosy gematologii/onkologii i immunopatologii v pediatrii = Pediatric Hematology/Oncology and Immunopathology. 2020;19(2):184–92. (In Russ.).Белышева Т.С., Алиев Т.З., Валиев Т.Т., Мачнева Е.Б., Сидорова Н.В., Мурашкин Н.Н., Киргизов К.И., Варфоломеева С.Р. Клинические особенности кожной формы острой реакции «трансплантат против хозяина» при аллогенной трансплантации гемопоэтических стволовых клеток у детей с онкогематологическими заболеваниями. Вопросы современной педиатрии. 2020;19(6):500–8. https://doi.org/10.15690/vsp.v19i6.2148.Belysheva T.S., Aliev T.Z., Valiev T.T., Machneva E.B., Sidorova N.V., Murashkin N.N., Kirgizov K.I., Varfolomeeva S.R. Clinical Features of Cutaneous Acute Graft-versus-Host Disease after Allogeneic Hematopoietic Stem Cells Transplantation in Children with HematoOncological Diseases. Voprosy sovremennoj pediatrii = Current Pediatrics. 2020;19(6):500–8. (In Russ.).Bolognia J.L., Cooper D.L., Glusac E.J. Toxic erythema of chemotherapy: a useful clinical term. J Am Acad Dermatol. 2008;59(3):524–9. doi: 10.1016/j.jaad.2008.05.018.Bolognia J.L., Cooper D.L., Glusac E.J. Toxic erythema of chemotherapy: a useful clinical term. J Am Acad Dermatol. 2008;59(3):524–9. doi: 10.1016/j.jaad.2008.05.018.Jagasia M.H., Greinix H.T., Arora M., Williams K.M., Wolff D., Cowen E.W., Palmer J., Weisdorf D., Treister N.S., Cheng G.S., Kerr H., Stratton P., Duarte R.F., McDonald G.B., Inamoto Y., Vigorito A., Arai S., Datiles M.B., Jacobsohn D., Heller T., Kitko C.L., Mitchell S.A., Martin P.J., Shulman H., Wu R.S., Cutler C.S., Vogelsang G.B., Lee S.J., Pavletic S.Z., Flowers M.E.D. National Institutes of Health Consensus Development Project on criteria for clinical trials in chronic graft-versus-host disease: I. The 2014 Diagnosis and Staging Working Group report. Biol Blood Marrow Transplant. 2015;21(3):389–401.e1. doi: 10.1016/j.bbmt.2014.12.001.Jagasia M.H., Greinix H.T., Arora M., Williams K.M., Wolff D., Cowen E.W., Palmer J., Weisdorf D., Treister N.S., Cheng G.S., Kerr H., Stratton P., Duarte R.F., McDonald G.B., Inamoto Y., Vigorito A., Arai S., Datiles M.B., Jacobsohn D., Heller T., Kitko C.L., Mitchell S.A., Martin P.J., Shulman H., Wu R.S., Cutler C.S., Vogelsang G.B., Lee S.J., Pavletic S.Z., Flowers M.E.D. National Institutes of Health Consensus Development Project on criteria for clinical trials in chronic graft-versus-host disease: I. The 2014 Diagnosis and Staging Working Group report. Biol Blood Marrow Transplant. 2015;21(3):389–401.e1. doi: 10.1016/j.bbmt.2014.12.001.Epstein J.B., Schubert M.M. Oropharyngeal mucositis in cancer therapy. Review of pathogenesis, diagnosis, and management. Oncology (Williston Park). 2003;17(12):1767–79; discussion 1779–82, 1791–2. PMID: 14723014.Epstein J.B., Schubert M.M. Oropharyngeal mucositis in cancer therapy. Review of pathogenesis, diagnosis, and management. Oncology (Williston Park). 2003;17(12):1767–79; discussion 1779–82, 1791–2. PMID: 14723014.Carreras E., Dufour C., Mohty M., Kröger N., eds. The EBMT Handbook: Hematopoietic Stem Cell Transplantation and Cellular Therapies [Internet]. 7th ed. Cham (CH): Springer, 2019. PMID: 32091673.Carreras E., Dufour C., Mohty M., Kröger N., eds. The EBMT Handbook: Hematopoietic Stem Cell Transplantation and Cellular Therapies [Internet]. 7th ed. Cham (CH): Springer, 2019. PMID: 32091673.Wachowiak J., Sykora K.W., Cornish J., Chybicka A., Kowalczyk J.R., Gorczyńska E., Choma M., Grund G., Peters C.; EBMT Pediatric Diseases Working Party. Treosulfan-based preparative regimens for allo-HSCT in childhood hematological malignancies: a retrospective study on behalf of the EBMT pediatric diseases working party. Bone Marrow Transplant. 2011;46(12):1510–8. doi: 10.1038/bmt.2010.343.Wachowiak J., Sykora K.W., Cornish J., Chybicka A., Kowalczyk J.R., Gorczyńska E., Choma M., Grund G., Peters C.; EBMT Pediatric Diseases Working Party. Treosulfan-based preparative regimens for allo-HSCT in childhood hematological malignancies: a retrospective study on behalf of the EBMT pediatric diseases working party. Bone Marrow Transplant. 2011;46(12):1510–8. doi: 10.1038/bmt.2010.343.Główka F.K., Romański M., Wachowiak J. High-dose treosulfan in conditioning prior to hematopoietic stem cell transplantation. Expert Opin Investig Drugs. 2010;19(10):1275–95. doi: 10.1517/13543784.2010.517744. PMID: 20836619.Główka F.K., Romański M., Wachowiak J. High-dose treosulfan in conditioning prior to hematopoietic stem cell transplantation. Expert Opin Investig Drugs. 2010;19(10):1275–95. doi: 10.1517/13543784.2010.517744. PMID: 20836619.Wachowiak J., Sykora K.W., Cornish J., Chybicka A., Kowalczyk J.R., Gorczynska E., Choma M., Grund G., Peters C. Treosulfan-based preparative regimens for allo-HSCT in childhood hematological malignancies: a retrospective study on behalf of the EBMT Pediatric Diseases Working Party. Bone Marrow Transplant. 2011;46:1510–8. doi: 10.1038/bmt.2010.343.Wachowiak J., Sykora K.W., Cornish J., Chybicka A., Kowalczyk J.R., Gorczynska E., Choma M., Grund G., Peters C. Treosulfan-based preparative regimens for allo-HSCT in childhood hematological malignancies: a retrospective study on behalf of the EBMT Pediatric Diseases Working Party. Bone Marrow Transplant. 2011;46:1510–8. doi: 10.1038/bmt.2010.343.Slatter M.A., Boztug H., Pötschger U., Sykora K.-W., Lankester A., Yaniv I., Sedlacek P., Glogova E., Veys P., Gennery A.R., Peters C., Inborn Errors EBMT, Parties PDW. Treosulfan-based conditioning regimens for allogeneic haematopoietic stem cell transplantation in children with non-malignant diseases. Bone Marrow Transplant. 2015;50:1536–41. doi: 10.1038/bmt.2015.171.Slatter M.A., Boztug H., Pötschger U., Sykora K.-W., Lankester A., Yaniv I., Sedlacek P., Glogova E., Veys P., Gennery A.R., Peters C., Inborn Errors EBMT, Parties PDW. Treosulfan-based conditioning regimens for allogeneic haematopoietic stem cell transplantation in children with non-malignant diseases. Bone Marrow Transplant. 2015;50:1536–41. doi: 10.1038/bmt.2015.171.Morillo-Gutierrez B., Beier R., Rao K., Burroughs L., Schulz A., Ewins A.M., Gibson B., Sedlacek P., Krol L., Strahm B., Zaidman I., Kalwak K., Talano J.A., Woolfrey A., Fraser C., Meyts I., Müller I., Wachowiak J., Bernardo M.E., Veys P., Sykora K.W., Gennery A.R., Slatter M. Treosulfan-based conditioning for allogeneic HSCT in children with chronic granulomatous disease: a multicenter experience. Blood. 2016;128(3):440–8. doi: 10.1182/ blood-2016-03-704015. Erratum in: Blood. 2016;128(21):2585. PMID: 27216217.Morillo-Gutierrez B., Beier R., Rao K., Burroughs L., Schulz A., Ewins A.M., Gibson B., Sedlacek P., Krol L., Strahm B., Zaidman I., Kalwak K., Talano J.A., Woolfrey A., Fraser C., Meyts I., Müller I., Wachowiak J., Bernardo M.E., Veys P., Sykora K.W., Gennery A.R., Slatter M. Treosulfan-based conditioning for allogeneic HSCT in children with chronic granulomatous disease: a multicenter experience. Blood. 2016;128(3):440–8. doi: 10.1182/ blood-2016-03-704015. Erratum in: Blood. 2016;128(21):2585. PMID: 27216217.Ten Brink M.H., Zwaveling J., Swen J.J., Bredius R.G., Lankester A.C., Guchelaar H.J. Personalized busulfan and treosulfan conditioning for pediatric stem cell transplantation: the role of pharmacogenetics and pharmacokinetics. Drug Discov Today. 2014;19(10):1572–86. doi: 10.1016/j.drudis.2014.04.005.Ten Brink M.H., Zwaveling J., Swen J.J., Bredius R.G., Lankester A.C., Guchelaar H.J. Personalized busulfan and treosulfan conditioning for pediatric stem cell transplantation: the role of pharmacogenetics and pharmacokinetics. Drug Discov Today. 2014;19(10):1572–86. doi: 10.1016/j.drudis.2014.04.005.Van der Stoep M.Y.E.C., Bertaina A., Ten Brink M.H., Bredius R.G., Smiers F.J., Wanders D.C.M., Moes D.J.A.R., Locatelli F., Guchelaar H.J., Zwaveling J., Lankester A.C. High interpatient variability of treosulfan exposure is associated with early toxicity in paediatric HSCT: a prospective multicentre study. Br J Haematol. 2017;179(5):772–80. doi: 10.1111/bjh.14960.Van der Stoep M.Y.E.C., Bertaina A., Ten Brink M.H., Bredius R.G., Smiers F.J., Wanders D.C.M., Moes D.J.A.R., Locatelli F., Guchelaar H.J., Zwaveling J., Lankester A.C. High interpatient variability of treosulfan exposure is associated with early toxicity in paediatric HSCT: a prospective multicentre study. Br J Haematol. 2017;179(5):772–80. doi: 10.1111/bjh.14960.Kearns G.L., Abdel-Rahman S.M., Alander S.W., Blowey D.L., Leeder J.S., Kauff man R.E. Developmental pharmacology–drug disposition, action, and therapy in infants and children. N Engl J Med. 2003;349(12):1157–67. doi: 10.1056/NEJMra035092.Kearns G.L., Abdel-Rahman S.M., Alander S.W., Blowey D.L., Leeder J.S., Kauff man R.E. Developmental pharmacology–drug disposition, action, and therapy in infants and children. N Engl J Med. 2003;349(12):1157–67. doi: 10.1056/NEJMra035092.Scheulen M.E., Hilger R.A., Oberhoff C., Casper J., Freund M., Josten K.M., Bornhäuser M., Ehninger G., Berdel W.E., Baumgart J., Harstrick A., Bojko P., Wolf H.H., Schindler A.E., Seeber S. Clinical phase I dose escalation and pharmacokinetic study of high-dose chemotherapy with treosulfan and autologous peripheral blood stem cell transplantation in patients with advanced malignancies. Clin Cancer Res. 2000;6(11):4209–16. PMID: 11106234.Scheulen M.E., Hilger R.A., Oberhoff C., Casper J., Freund M., Josten K.M., Bornhäuser M., Ehninger G., Berdel W.E., Baumgart J., Harstrick A., Bojko P., Wolf H.H., Schindler A.E., Seeber S. Clinical phase I dose escalation and pharmacokinetic study of high-dose chemotherapy with treosulfan and autologous peripheral blood stem cell transplantation in patients with advanced malignancies. Clin Cancer Res. 2000;6(11):4209–16. PMID: 11106234.Rosman I.S., Lloyd B.M., Hayashi R.J, Bayliss S.J. Cutaneous effects of thiotepa in pediatric patients receiving high-dose chemotherapy with autologous stem cell transplantation. J Am Acad Dermatol. 2008;58(4):575–8. doi: 10.1016/j.jaad.2007.12.037.Rosman I.S., Lloyd B.M., Hayashi R.J, Bayliss S.J. Cutaneous eff ects of thiotepa in pediatric patients receiving high-dose chemotherapy with autologous stem cell transplantation. J Am Acad Dermatol. 2008;58(4):575–8. doi: 10.1016/j.jaad.2007.12.037.Tkachenko P.E., Ivashkin V.T., Maevskaya M.V. Clinical guidelines for the correction of hepatotoxicity induced by anticancer therapy. Malignant tumors. 2020;10(3s2-2):52–65. doi: 10.18027/2224-5057-2020-10-3s2-40.Tkachenko P.E., Ivashkin V.T., Maevskaya M.V. Clinical guidelines for the correction of hepatotoxicity induced by anticancer therapy. Malignant tumors. 2020;10(3s2-2):52–65. doi: 10.18027/2224-5057-2020-10-3s2-40.Иваников И.О., Виноградова Н.Н., Крашенков О.П., Коцелапова Э.Ю., Григорьева Ю.В., Мясникова Е.В., Пикунова И.Н. Острые повреждения печени вследствие химиотерапии и возможности их лечения. Доказательная гастроэнтерология. 2020;9(4):7–15. doi: 10.17116/dokgastro202090417.Ivanikov I.O., Vinogradova N.N., Krashenkov O.P., Kotselapova E.Yu., Grigorieva Yu.V., Myasnikova E.V., Pikunova I.N. Treatment of the chemotherapy induced hepatotoxicity. Dokazatel’naya gastroenterologiya = Russian Journal of EvidenceBased Gastroenterology. 2020;9(4):7–15. (In Russ.).Levi M., Stemmer S.M., Stein J., Shalgi R., Ben-Aharon I. Treosulfan induces distinctive gonadal toxicity compared with busulfan. Oncotarget. 2018;9(27):19317–27. doi: 10.18632/oncotarget.25029.Levi M., Stemmer S.M., Stein J., Shalgi R., Ben-Aharon I. Treosulfan induces distinctive gonadal toxicity compared with busulfan. Oncotarget. 2018;9(27):19317–27. doi: 10.18632/oncotarget.25029.Feit P.W., Rastrup-Andersen N., Matagne R. Studies on epoxide formation from (2S,3S)-threitol 1,4-bismethanesulfonate. The preparation and biological activity of (2S,3S)-1,2-epoxy-3,4- butanediol 4-methanesulfonate. J Med Chem. 1970;13(6):1173–5. doi: 10.1021/jm00300a034. PMID: 5479859.Feit P.W., Rastrup-Andersen N., Matagne R. Studies on epoxide formation from (2S,3S)-threitol 1,4-bismethanesulfonate. The preparation and biological activity of (2S,3S)-1,2-epoxy-3,4- butanediol 4-methanesulfonate. J Med Chem. 1970;13(6):1173–5. doi: 10.1021/jm00300a034. PMID: 5479859.Romański M., Ratajczak W., Główka F. Kinetic and mechanistic study of the pH-dependent activation (epoxidation) of prodrug treosulfan including the reaction inhibition in a borate buff er. J Pharm Sci. 2017;106:1917–22. doi: 10.1016/j.xphs.2017.03.018.Romański M., Ratajczak W., Główka F. Kinetic and mechanistic study of the pH-dependent activation (epoxidation) of prodrug treosulfan including the reaction inhibition in a borate buff er. J Pharm Sci. 2017;106:1917–22. doi: 10.1016/j.xphs.2017.03.018.

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