The role and place of high-dose immunosuppressive therapy and autologous transplantation of hematopoietic stem cells for autoimmune diseases

Abstract

Aim. To determine the possible boundaries of high-dose immunosuppressive therapy and autologous hematopoietic stem cell transplantation (HDIT-autoHSCT) for autoimmune diseases (AUDs), such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and multiple sclerosis (MS). Subjects and methods. A long-term trial was conducted at one center to evaluate the efficiency and safety of HDIT-autoHSCT in patients with AUDs. The previous standard therapy was noted to be resistant or lowly effective. The age of 10 patients with systemic connective tissue diseases was 27.6±2.8 years; the pre-HDIT-autoHSCT disease duration was 5.9±1.3 years; the median posttransplantation follow-up was 39.3 months. The age of 49 patients with MS reached 34.9±1.33 years; the pretransplantation disease duration was 8.4±0.69 years; the median post-HDIT-autoHSCT follow-up was 42 months. The efficiency of transplantation was evaluated on the basis of clinical findings, by using scales, laboratory tests, and magnetic resonance imaging. Pretransplantation conditioning was carried out according to the protocols: a) BEAM + antilymphocyte globulin (ALG); b) fludarabine + melphalan + ALG. No fatal outcomes due to a transplant procedure were observed. Results. Overall 5-year survival after transplantation was 80% for systemic connective tissue diseases and 95% for MS; 5-year progression-free survival rates were 30% in the RA and SLE groups and 45% in the MS group. HDIT-autoHSCT turned out safe and reduced the activity of the process and further disease progression for a long period of time, as confirmed by regression of clinical symptoms and/or status stabilization in 9 patients with SLE or RA and in all patients with MS. Conclusion. The favorable factors associated with the results of transplantation are age younger than 35 years in collagenoses with their short-term duration and moderate signs; age younger than 40 years in MS with a disease duration of less than 10 years and expanded disability status scale scores of not more than 6.5. Of importance are functional system scores, duration of first remission, and an index of disease progression in different types of MS.

References

  1. Шмитд Т.Е. Лечение рассеянного склероза в стадии прогрессирования. В кн: Шмитд Т.Е., Яхно Н.Н. Рассеянный склероз: руководство для врачей. М.: МЕДпресс-информ; 2012.
  2. Davis JM, Maradit Kremers H, Crowson CS, Nicola PJ, Ballman KV, Therneau TM, Roger VL, Gabriel SE. Glucocorticoids and cardiovascular events in rheumatoid arthritis: a population-based cohort study. Arthritis Rheum. 2007;56(3):820-830. doi: 10.1002/art.22418.
  3. Kang I, Park SH. Infectious complications in SLE after immuno-suppressive therapies. Cur Opin Rheumatol. 2003;15(5):528-534. doi: 10.1097/00002281-200309000-00002.
  4. Mancardi GL, Sormani MP, Di Gioia M, Vuolo L, Gualandi F, Amato MP, Capello E, Currò D, Uccelli A, Bertolotto A, Gasperini C, Lugaresi A, Merelli E, Meucci G, Motti L, Tola MR, Scarpini E, Repice AM, Massacesi L, Saccardi R. Autologous haematopoietic stem cell transp-lantation with an intermediate intensity conditioning regimen in multiple sclerosis: the Italian multi-centre experience. Multiple Sclerosis J. 2012;18(6):835-842. doi: 10.1177/1352458511429320.
  5. Farge D, Labopin M, Tyndall A, Fassas A, Mancardi GL, Van Laar J, Ouyang J, Kozak T, Moore J, Kötter I, Chesnel V, Marmont A, Gratwohl A, Saccardi R. Autologous hematopoietic stem cell transplantation for autoimmune diseases: an observational study on 12 years’ experience from the European Group for Blood and Marrow Transplantation Working Party on Autoimmune Diseases. Haematologica. 2010;95(2):284-292. doi: 10.3324/haematol.2009.013458.
  6. Snowden JA, Passweg J, Moore JJ, Milliken S, Cannell P, Van Laar J, Verburg R, Szer J, Taylor K, Joske D, Rule S, Bingham SJ, Emery P, Burt RK., Lowenthal RM., Durez P, McKendry RJ, Pavletic SZ, Espigado I, Jantunen E, Kashyap A, Rabusin M, Brooks P, Bredeson C, Tyndall A. Autologous hemopoietic stem cell transplantation in severe rheumatoid arthritis: a report from the EBMT and ABMTR. J Rheumatol. 2004;31(3):482-488.
  7. Углов Б.А., Котельников Г.П., Углова М.В. Основы статистического анализа и математического моделирования в медико-биологических исследованиях. Самара: СамГМУ; 1994.
  8. Осина И.Г., Россиев В.А., Караулов А.В. Новые технологии в диагностике и лечении аутоиммунных заболеваний. Самара: НТЦ; 2007.
  9. Демин А.А., Козлов В.А., Лисуков И.А. Сентякова Т.Н., Кулагин А.Д., Крючкова И.В., Сизиков А.Э., Сизикова С.А., Коненкова Л.П., Герцог О.А., Сергеевичева В.В., Котова О.С. Отдаленные результаты ауто-трансплантации стволовых кроветворных клеток при резистентной системной красной волчанке. Сибирский медицинский журнал. 2011;1:86-89.
  10. Мельниченко В.Я., Россиев В.А., Афанасьев Б.В., Рукавицин О.А., Макаров С.В., Новик А.А., Федоренко Д.А., Шаманский С.В., Ионова Т.И., Лисуков И.А., Кулагин А.Д., Курбатов К.А., Ефремов А.Г., Осипова Н.А. Российский опыт лечения больных рассеянным склерозом высокодозной иммуносупрессивной терапией с аутотрансплантацией стволовых кроветворных клеток. Гематология и трансфузиология. 2012;3(прил. «Материалы Конгресса гематологов России», [2—4 июля 2012 г., Москва]:63.
  11. Novik A, Kuznetsov A, Afanasyev B, Rossiev V, Lisukov I. Long-term follow-up after autologous haematopoietic stem cell transplantation for multiple sclerosis. Bone Marrow Transplantation. 2011;46(1):85.
  12. Шевченко Ю.Л., Кузнецов Ф.Н., Федотов Ю.Н. Мельниченко В.Я., Ионова Т.И., Федоренко Д.А., Карташов А.В., Круглина Р.В., Курбатова К.А., Новик А.А. Варианты стратегии высокодозной иммуносупрессивной терапии с трансплантацией кроветворных стволовых клеток при рассеянном склерозе: результаты длительного мониторинга. Вестник национального медико-хирургического центра им. Н.И. Пирогова. 2012;2:3-8.
  13. Макаров С.В., Россиев В.А., Ефремов А.Г., Липина Л.Н., Торопова Н.Е. Комплексная оценка результатов высокодозной иммуносупрессивной терапии и аутотрансплантации стволовых кроветворных клеток у больных рассеянным склерозом со вторично-прогрессирующим течением заболевания. Неврологический журнал. 2005;2:18-23.
  14. Makarov SV, Rossiev VA, Efremov AG. Clinical results of high-dose immunosupressive therapy with autologous stem cell transplantation in treatment of autoimmune diseases of the neurological system. Eur J Neurol. 2011;18(2):531.
  15. Saccardi R, Kozak T, Bocelli-Tyndall C, Fassas A, Kazis A, Havrdova E, Carreras E, Saiz A, Löwenberg B, te Boekhorst PA, Gualandio F, Openshaw H, Longo G, Pagliai F, Massacesi L, Deconink E, Ouyang J, Nagore FJ, Besalduch J, Lisukov IA, Bonini A, Merelli E, Slavino S, Gratwohl A, Passweg J, Tyndall A, Steck A, Andolina M, Capobianco M, Martin JL, Lugaresi A, Meucci G, Sáez RA, Clark RE, Fernandez MN, Fouillard L, Herstenstein B, Koza V, Cocco E, Baurmann H, Mancardi GL. Autologous stem cell transplantation for progressive multiple sclerosis: update of the European Group for Blood and Marrow Transplantation autoimmune diseases working party database. Multiple Sclerosis. 2006;12(6):814-823. doi: 10.1177/1352458506071301.
  16. Bowen JD, Kraft GH, Wundes A, Guan Q, Maravilla KR, Gooley TA, McSweeney PA, Pavletic SZ, Openshaw H, Storb R, Wener M, McLaughlin BA, Henstorf GR, Nash RA. Autologous hematopoietic cell transplantation following high-dose immunosuppressive therapy for advanced multiple sclerosis: long-term results. Bone Marrow Transplantation. 2012;47(7):946-951. doi: 10.1038/bmt.2011.208.
  17. Mancardi GL, Murialdo A, Rossi P, Gualandi F, Martino G, Marmont A, Ciceri F, Schenone A, Parodi RC, Capello E, Comi G, Uccelli A. Autologous stem cell transplantation as rescue therapy in malignant forms of multiple sclerosis. Multiple Sclerosis. 2005;11(3):367-371. doi: 10.1191/1352458505ms1181cr.
  18. Fagius J, Lundgren J, Oberg G. Early highly aggressive MS succes-sfully treated by hematopoietic stem cell transplantation. Multiple Sclerosis. 2009;15(2):229-237. doi: 10.1177/1352458508096875.
  19. Radaelli M, Merlini A, Greco R, Sangalli F, Comi G, Ciceri F, Martino G. Autologous bone marrow transplantation for the treatment of multiple sclerosis. Cur Neurol Neuroscie Reports. 2014;14(9):478. doi: 10.1007/s11910-014-0478-0.
  20. Rogojan C, Frederiksen JL. Hematopoietic stem cell transplantation in multiple sclerosis. Acta Neurologica Scandinavica. 2009;120(6):371-382. doi: 10.1111/j.1600-0404.2009.01168.x.
  21. «ВП-П8-2322. Комплексная программа развития биотехнологий в Российской Федерации на период до 2020 года» (утв. Правительством РФ 24.04.2012 №1853п-П8) Доступно по: http://government.ru/media/files/41d4e85f0b854eb1b02d.pdf. Ссылка активна на 08.10.2015.
  22. Распоряжение Правительства РФ №2580-р от 28.12.2012 «Об утверждении Стратегии развития медицинской науки в Российской Федерации на период до 2025 года». http://www.rosminzdrav.ru/documents/5413-rasporyazhenie-pravitelstva-rossiyskoy-federatsii-ot-28-dekabrya-2012-g-n-2580-r. Ссылка активна на 08.10.2015.

Copyright (c) 2016 Makarov S.V., Rossiev V.A., Mishchenko O.V., Kozlov V.A., Semagina O.V., Alexandrova I.Y., Grishina G.V., Minaev Y.L.

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