Possibilities of hematopoietic stem cells transplantation in the treatment of systemic scleroderma

1. Van den Hoogen F, Khanna D, Fransen J, Johnson S, Baron M, Tyndall A et al. 2013 classification criteria for systemic sclerosis: An American College of Rheumatology / European League against Rheumatism collaborative initiative. Arthritis Rheum. 2013;65(11):2737–47.

PMID: 24122180. PMCID: PMC3930146. https://doi.org/10.1002/art.38098

2. Volkmann E, Andreasson K, Smith V. Systemic sclerosis. Lancet. 2023;401(10373):304–18.

PMID: 36442487. PMCID: PMC9892343. https://doi.org/10.1016/s0140-6736(22)01692-0

3. Трофимова А.С., Шохин А.А., Трофимов Е.А., Шостак М.С. Клинический случай системной склеродермии у мужчины: гендерные различия и возможности капилляроскопии. Современная ревматология. 2024;18(1):84–89. (Trofimova AS, Shokhin AA, Trofimov EA, Shostak MS. Clinical case of systemic sclerosis in a male patient: Gender differences and possibilities of capillaroscopy. Sovremennaya revmatologiya = Modern Rheumatology Journal. 2024;18(1):84–89 (In Russ.)).

EDN: JPIBTM. https://doi.org/10.14412/1996-7012-2024-1-84-89

4. Farge D, Pugnet G, Allez M, Castilla-Llorente C, Chatelus E, Cintas P et al. French protocol for the diagnosis and management of hematopoietic stem cell transplantation in autoimmune diseases. Rev Med Interne. 2024;45(2):79–99.

PMID: 38220493. https://doi.org/10.1016/j.revmed.2023.12.008

5. Cavazzana I, Vojinovic T, Airo’ P, Fredi M, Ceribelli A, Pedretti E et al. Systemic sclerosis-specific antibodies: Novel and classical biomarkers. Clin Rev Allergy Immunol. 2023;64(3):412–30.

PMID: 35716254. PMCID: PMC10167150. https://doi.org/10.1007/s12016-022-08946-w

6. Bergamasco A, Hartmann N, Wallace L, Verpillat P. Epidemiology of systemic sclerosis and systemic sclerosis-associated interstitial lung disease. Clin Epidemiol. 2019;11:257–73.

PMID: 31114386. PMCID: PMC6497473. https://doi.org/10.2147/CLEP.S191418

7. De Almeida Chaves S, Porel T, Mounie M, Alric L, Astudillo L, Huart A et al. Sine scleroderma, limited cutaneous, and diffused cutaneous systemic sclerosis survival and predictors of mortality. Arthritis Res Ther. 2021;23(1):295.

PMID: 34876194. PMCID: PMC8650544. https://doi.org/10.1186/s13075-021-02672-y

8. Lee YH. Overall and sex-and disease subtype-specific mortality in patients with systemic sclerosis. Zeitsch Rheumatol. 2019;78(2):195–201.

PMID: 29869154. https://doi.org/10.1007/s00393-018-0492-8

9. Elhai M, Meune C, Boubaya M, Avouac J, Hachulla E, Balbir-Gurman A et al.; EUSTAR group. Mapping and predicting mortality from systemic sclerosis. Ann Rheum Dis. 2017;76(11):1897–905.

PMID: 28835464. https://doi.org/10.1136/annrheumdis-2017-211448

10. Namas R, Tashkin DP, Furst DE, Wilhalme H, Tseng CH, Roth MD et al.; Participants in the Scleroderma Lung Study I and members of the Scleroderma Lung Study II Research Group. Efficacy of mycophenolate mofetil and oral cyclophosphamide on skin thickness: Post hoc analyses from two randomized placebo-controlled trials. Arthritis Care Res (Hoboken) 2018;70(3):439–44.

PMID: 28544580. PMCID: PMC5700860. https://doi.org/10.1002/acr.23282

11. Zacay G, Levy Y. Outcomes of patients with systemic sclerosis treated with tocilizumab: Case series and review of the literature. Best Pract Res Clin Rheumatol. 2018;32(4):563–71.

PMID: 31174825. https://doi.org/10.1016/j.berh.2019.01.011

12. Ананьева Л.П., Конева О.А., Десинова О.В., Гарзанова Л.А., Глухова С.И., Старовойтова М.Н. с соавт. Влияние ритуксимаба на проявления активности и легочную функцию у больных системной склеродермией: оценка после года наблюдения. Научно-практическая ревматология. 2019;57(3):265–73. (Ananyeva LP, Koneva OA, Desinova OV, Garzanova LA, Glukhova SI, Starovoitova MN et al. Effect of rituximab on the manifestations of activity and pulmonary function in patients with systemic sclerosis: One-year follow-up evaluation. Nauchno-prakticheskaya revmatologiya = Rheumatology Science and Practice. 2019;57(3):265–73 (In Russ.)).

EDN: VSANGM. https://doi.org/10.14412/1995-4484-2019-265-273

13. Goldin J, Kim G, Tseng C, Volkmann E, Furst D, Clements P et al. Longitudinal changes in quantitative interstitial lung disease on computed tomography after immunosuppression in the Scleroderma Lung Study II. Ann Am Thorac Soc. 2018;15(11):1286–95.

PMID: 30265153. PMCID: PMC6322015. https://doi.org/10.1513/AnnalsATS.201802-079OC

14. Marmont A, van Lint M, Gualandi F, Bacigalupo A. Autologous marrow stem cell transplantation for severe systemic lupus erythematosus of long duration. Lupus. 1997;6(6):545–48.

PMID: 9256315. https://doi.org/10.1177/096120339700600613

15. Oliveira MC, Elias JB, Moraes DA, Simoes BP, Rodrigues M, Ribeiro AAF et al. A review of hematopoietic stem cell transplantation for autoimmune diseases: Multiple sclerosis, systemic sclerosis and Crohn’s disease. Position paper of the Brazilian Society of Bone Marrow Transplantation. Hematol Transfus Cell Ther. 2021;43(1):65–86.

PMID: 32418777. PMCID: PMC7910166. https://doi.org/10.1016/j.htct.2020.03.002

16. Alexander T, Greco R. Hematopoietic stem cell transplantation and cellular therapies for autoimmune diseases: overview and future considerations from the Autoimmune Diseases Working Party (ADWP) of the European Society for Blood and Marrow Transplantation (EBMT). Bone Marrow Transplant. 2022;57(7):1055–62.

PMID: 35578014. PMCID: PMC9109750. https://doi.org/10.1038/s41409-022-01702-w

17. Snowden JA, Badoglio M, Labopin M, Giebel S, McGrath E, Marjanovic Z et al.; European Society for Blood and Marrow Transplantation (EBMT) Autoimmune Diseases Working Party (ADWP); EBMT Paediatric Working Party (PWP); Joint Accreditation Committee of the International Society for Cellular Therapy (ISCT); EBMT (JACIE). Evolution, trends, outcomes, and economics of hematopoietic stem cell transplantation in severe autoimmune diseases. Blood Adv. 2017;1(27):2742–55.

PMID: 29296926. PMCID: PMC5745133. https://doi.org/10.1182/bloodadvances.2017010041

18. Farge D, Marolleau J, Zohar S, Marjanovic Z, Cabane J, Mounier N et al.; Intensification et Autogreffe dans les Maladies Auto Immunes Resistantes (ISAMAIR) Study Group. Autologous bone marrow transplantation in the treatment of refractory systemic sclerosis: Early results from a French multicentre phase I–II study. Br J Haematol. 2002;119(30:726–39.

PMID: 12437652. https://doi.org/10.1046/j.1365-2141.2002.03895.x

19. Vonk M, Marjanovic Z, van den Hoogen F, Zohar S, Schattenberg A, Fibbe W et al. Long-term follow-up results after autologous haematopoietic stem cell transplantation for severe systemic sclerosis. Ann Rheum Dis. 2008;67(1):98–104.

PMID: 17526554. https://doi.org/10.1136/ard.2007.071464

20. Burt R, Shah S, Dill K, Grant T, Gheorghiade M, Schroeder J et al. Autologous non-myeloablative haemopoietic stem-cell transplantation compared with pulse cyclophosphamide once per month for systemic sclerosis (ASSIST): An open-label, randomised phase 2 trial. Lancet. 2011;378(9790):498–506.

PMID: 21777972. https://doi.org/10.1016/S0140-6736(11)60982-3

21. Sullivan K, Goldmuntz E, Keyes-Elstein L, McSweeney P, Pinckney A, Welch B et al.; SCOT Study Investigators. Myeloablative autologous stem-cell transplantation for severe scleroderma. N Engl J Med. 2018;378(1):35–47.

PMID: 29298160. PMCID: PMC5846574. https://doi.org/10.1056/nejmoa1703327

22. Duarte RF, Labopin M, Bader P, Basak GW, Bonini C, Chabannon C et al.; European Society for Blood and Marrow Transplantation (EBMT). Indications for haematopoietic stem cell transplantation for haematological diseases, solid tumours and immune disorders: Current practice in Europe, 2019. Bone Marrow Transplant. 2019;54(10):1525–52.

PMID: 30953028. https://doi.org/10.1038/s41409-019-0516-2

23. Del Galdo F, Lescoat A, Conaghan PG, Bertoldo E, Colic J, Santiago T et al. EULAR recommendations for the treatment of systemic sclerosis: 2023 update. Ann Rheum Dis. 2025;84(1):29–40.

PMID: 39874231. https://doi.org/10.1136/ard-2024-226430

24. Sullivan KM, Majhail NS, Bredeson C, Carpenter PA, Chatterjee S, Crofford LJ et al. Systemic sclerosis as an indication for autologous hematopoietic cell transplantation: Position Statement from the American Society for Blood and Marrow Transplantation. Biol Blood Marrow Transplant. 2018;24(10):1961–64.

PMID: 29953945. PMCID: PMC6239926. https://doi.org/10.1016/j.bbmt.2018.06.025

25. van Laar JM, Farge D, Sont JK, Naraghi K, Marjanovic Z, Larghero J et al.; EBMT/EULAR Scleroderma Study Group. Autologous hematopoietic stem cell transplantation vs intravenous pulse cyclophosphamide in diffuse cutaneous systemic sclerosis: A randomized clinical trial. JAMA. 2014;311(24):2490–98.

PMID: 25058083. https://doi.org/10.1001/jama.2014.6368

26. Aghel N, Lui M, Wang V, Khalaf D, Mian H, Hillis C et al. Cardiovascular events among recipients of hematopoietic stem cell transplantation – a systematic review and meta-analysis. Bone Marrow Transplant. 2023;58(5):478–90.

PMID: 36849807. https://doi.org/10.1038/s41409-023-01928-2

27. Burt RK, Oliveira MC, Shah SJ, Moraes DA, Simoes B, Gheorghiade M et al. Cardiac involvement and treatment-related mortality after non-myeloablative haemopoietic stem-cell transplantation with unselected autologous peripheral blood for patients with systemic sclerosis: A retrospective analysis. Lancet. 2013;381(9872):1116–24.

PMID: 23363664. https://doi.org/10.1016/S0140-6736(12)62114-X

28. Burt R, Farge D. Systemic sclerosis: Autologous HSCT is efficacious, but can we make it safer? Nat Rev Rheumatol. 2018;14(4):189–91.

PMID: 29515186. https://doi.org/10.1038/nrrheum.2018.34

29. Farge D, Burt RK, Oliveira MC, Mousseaux E, Rovira M, Marjanovic Z et al. Cardiopulmonary assessment of patients with systemic sclerosis for hematopoietic stem cell transplantation: Recommendations from the European Society for Blood and Marrow Transplantation Autoimmune Diseases Working Party and collaborating partners. Bone Marrow Transplant. 2017;52(11):1495–503.

PMID: 28530671. PMCID: PMC5671927. https://doi.org/10.1038/bmt.2017.56

30. Tyndall A, Gratwohl A. Blood and marrow stem cell transplants in autoimmune disease: a consensus report written on behalf of the European League against Rheumatism (EULAR) and the European Group for Blood and Marrow Transplantation (EBMT). Bone Marrow Transplant. 1997;19(7):643–45.

PMID: 9156239. https://doi.org/10.1038/sj.bmt.1700727

31. Zanin-Silva DC, Santana-Gonçalves M, Kawashima-Vasconcelos MY, Lima-Júnior JR, Dias JBE et al. Autologous hematopoietic stem cell transplantation promotes connective tissue remodeling in systemic sclerosis patients. Arthritis Res Ther. 2022;24(1):95.

PMID: 35488348. PMCID: PMC9052524. https://doi.org/10.1186/s13075-022-02779-w

32. Santana-Gonçalves M, Zanin-Silva D, Henrique-Neto A, Moraes DA, Kawashima-Vasconcelos MY, Lima-Junior JR et al. Autologous hematopoietic stem cell transplantation modifies specific aspects of systemic sclerosis-related microvasculopathy. Ther Adv Musculoskelet Dis. 2022;14:1759720X221084845.

PMID: 35368373. PMCID: PMC8966069. https://doi.org/10.1177/1759720X221084845

33. Bagnato G, Versace AG, La Rosa D, De Gaetano A, Imbalzano E, Chiappalone M et al. Autologous haematopoietic stem cell transplantation and systemic sclerosis: Focus on interstitial lung disease. cells. 2022;11(5):843.

PMID: 35269465. PMCID: PMC8909673. https://doi.org/10.3390/cells11050843

34. van Bijnen S, de Vries-Bouwstra J, van den Ende CH, Boonstra M, Kroft L, Geurts B et al. Predictive factors for treatment-related mortality and major adverse events after autologous hematopoietic stem cell transplantation for systemic sclerosis: Results of a long-term follow-up multicenter study. Ann Rheum Dis. 2020;79(8):1084–89.

PMID: 32409324. https://doi.org/10.1136/annrheumdis-2020-217058

35. Panopoulos S, Tektonidou M, Bournia V, Laskari K, Sfikakis P. Outcomes of conventionally-treated systemic sclerosis patients eligible for autologous hematopoietic stem cell transplantation. Clin Exp Rheumatol. 2021;39 Suppl131(4):29–33.

PMID: 33200737. https://doi.org/10.55563/clinexprheumatol/dhn3mb

36. Henes J, Oliveira MC, Labopin M, Badoglio M, Scherer HU, Del Papa N et al. Autologous stem cell transplantation for progressive systemic sclerosis: A prospective non-interventional study from the European Society for Blood and Marrow Transplantation Autoimmune Disease Working Party. Hematologica. 2021;106(2):375–83.

PMID: 31949011. PMCID: PMC7849556. https://doi.org/10.3324/haematol.2019.230128

37. Alexander T, Roldan E, Del Papa N, Farge D, Henes J, Marjanovic Z et al. Autologous hematopoietic stem cell transplantation for rheumatic diseases: Best practice recommendations from the EBMT Practice Harmonization and Guidelines Committee. Bone Marrow Transplant. 2025;60(11):1451– 64.

PMID: 40830237. PMCID: PMC12583147. https://doi.org/10.1038/s41409-025-02695-y

38. Мазуров В.И., Маслянский А.Л., Зоткина К.Е., Беневоленская С.С., Моторин Д.В., Зарицкий А.Ю. с соавт. Опыт успешного применения аутологичной трансплантации стволовых гемопоэтических клеток у пациенток с неблагоприятным прогнозом течения диффузной формы системной склеродермии. Научно-практическая ревматология. 2022;60(3):381–387. (Mazurov VI, Maslyanskiy AL, Zotkina KE, Benevolenskaya SS, Motorin DV, Zaritskiy AYu et al. Experience of successful autologous hematopoietic stem cell transplantation in patients with an unfavorable prognosis of systemic scleroderma. Nauchno-prakticheskaya revmatologia = Rheumatology Science and Practice. 2022;60(3):381–387 (In Russ.)).

EDN: XLVMBS. https://doi.org/10.47360/1995-4484-2022-381-387

39. Farge D, Ait Abdallah N, Marjanovic Z, Del Papa N. Autologous stem cell transplantation in scleroderma. Presse Med. 2021;50(1):104065.

PMID: 33548374. https://doi.org/10.1016/j.lpm.2021.104065

40. Sharrack B, Saccardi R, Alexander T, Badoglio M, Burman J, Farge D et al.; European Society for Blood and Marrow Transplantation (EBMT) Autoimmune Diseases Working Party (ADWP) and the Joint Accreditation Committee of the International Society for Cellular Therapy (ISCT) and EBMT (JACIE). Autologous haematopoietic stem cell transplantation and other cellular therapy in multiple sclerosis and immune-mediated neurological diseases: updated guidelines and recommendations from the EBMT Autoimmune Diseases Working Party (ADWP) and the Joint Accreditation Committee of EBMT and ISCT (JACIE). Bone Marrow Transplant. 2020;55(2):283–306.

PMID: 31558790. PMCID: PMC6995781. https://doi.org/10.1038/s41409-019-0684-0

41. Denton CP, De Lorenzis E, Roblin E, Goldman N, Alcacer-Pitarch B, Blamont E et al. The 2024 British Society for Rheumatology guideline for management of systemic sclerosis. Rheumatology (Oxford). 2024;63(11):2956–75.

PMID: 39255973. PMCID: PMC11534099. https://doi.org/10.1093/rheumatology/keae394

42. Spierings J, van Rhenen A, Welsing PM, Marijnissen AC, De Langhe E, Del Papa N et al. A randomised, open-label trial to assess the optimal treatment strategy in early diffuse cutaneous systemic sclerosis: The UPSIDE study protocol. BMJ Open. 2021;11(3):e044483.

PMID: 33737437. PMCID: PMC7978271. https://doi.org/10.1136/bmjopen-2020-044483

43. Alexander T, Roldan E, Del Papa N, Farge D, Henes J, Marjanovic Z et al. Autologous haematopoietic stem cell transplantation for rheumatic diseases: best practice recommendations from the EBMT Practice Harmonization and Guidelines Committee. Bone Marrow Transplant. 2025;60(11):1451–64.

PMID: 40830237. PMCID: PMC12583147. https://doi.org/10.1038/s41409-025-02695-y

44. Burt R, Han X, Quigley K, Arnautovic I, Shah S, Lee D et al. Cardiac safe hematopoietic stem cell transplantation for systemic sclerosis with poor cardiac function: A pilot safety study that decreases neutropenic interval to 5 days. Bone Marrow Transpl. 2021;56(1):50–59.

PMID: 32612255. https://doi.org/10.1038/s41409-020-0978-2