Emerging use of Stem Cell Transplants for Systemic Sclerosis
Main Article Content
Abstract
Over the last 20 years stem cell transplant (SCT) has shown promising results in a variety of autoimmune rheumatologic disorders. Of these conditions, systemic sclerosis (SSc) has garnered the most attention given the limited alternative options for advanced disease. Several early studies and now several randomized controlled trials have demonstrated improved skin, lung, and vascular outcomes. However complications associated with the immunoablating steps in the transplant process have led to cardiotoxicity, infections, and death in some transplant recipients. Growing efforts are being made to examine how to optimize the transplant process to improve safety but retain efficacy.
Article Details
How to Cite
MASCARENHAS, Sheryl.
Emerging use of Stem Cell Transplants for Systemic Sclerosis.
Medical Research Archives, [S.l.], v. 4, n. 6, oct. 2016.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/714>. Date accessed: 17 nov. 2024.
Keywords
stem cell transplant; systemic sclerosis
Section
Review Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
1. Prescott RJ, Freemont AJ, Jones CJ, et al. Sequential dermal microvascular and perivascular changes in the development of scleroderma. J Pathol. 1992;166(3):255–63.
2. Hu H, Stein-Streilein J. Hapten-immune pulmonary interstitial fibrosis (HIPIF) in mice requires both CD4+ and CD8+ T lymphocytes. J Leukoc Biol. 1993;54(5):414–22.
3. Rosa SB, Voltarelli JC, Chies JA, et al. The use of stem cells for the treatment of autoimmune diseases. Braz J Med Biol Res. 2007;40(12):1579–97.
4. Denton CP. Systemic sclerosis: from pathogenesis to targeted therapy. Clin Exp Rheumatol. 2015;33(4Suppl 92):S3-7.
5. Ioannidis JP, Vlachoyiannopoulos PG, Haidich AB, et al. Mortality in systemic sclerosis: an international meta-analysis of individual patient data. Am J Med.2005;118:2–10
6. Mascarenhas S, Avalos B, & Ardoin SP, An Update on Stem Cell Transplantation in Autoimmune Rheumatologic Disorders. Curr Allergy Asthma Rep. 2012;12(6):530-540.
7. Sykes M & Nikolic B. Treatment of severe autoimmune disease by stem-cell transplantation. Nature.2005;435;620-627.
8. DiPersio JF, Micallef IN, Stiff PJ, et al. Phase III Prospective Randomized Double-Blind Placebo-Controlled Trial of Plerixafor Plus Granulocyte Colony-Stimulating Factor Compared with Placebo Plus Granulocyte Colony-Stimulating Factor for Autologous Stem-Cell Mobilization and Transplantation for Patients with Non-Hodgkin’s Lymphoma. J Clin Oncol. 2009;27(28):4767–73.
9. Moore J, Brooks P, Milliken S, et al. A pilot randomized trial comparing CD34-selected versus unmanipulated hematopoietic stem cell transplantation for severe refractory rheumatoid arthritis. Arthritis Rheum. 2002;46(9):2301–9.
10. Kelsy PJ, Oliveira MC, Badogolio M, et al. Haematopoietic stem cell transplantation in autoimmune diseases: From basic science to clinical practice. Curr Res Transl Med. 2016;64(2):71-82.
11. Nash RA, McSweeney PA, Crofford LJ, et al. High-dose immunosuppressive therapy and autologous hematopoietic cell transplantation for severe systemic sclerosis: long-term follow-up of the US multicenter pilot study. Blood. 2007;110-1388-96
12. Oyama Y, Barr WG, Statkute L, et al. Autologous non-myeloablative hematopoietic stem cell transplantation in patients with systemic sclerosis. Bone Marrow Transplant. 2007;40(6):549-55.
13. Henes JC, Schmalzing M, Vogel W, et al. Optimization of autologous stem cell transplantation for systemic sclerosis: a single-center long-term experience in 26 patients with severe organ manifestations. J Rheumatol. 2012; 39:269–275
14. Burt RK, Shah SJ, Dill K, et al. Autologous non-myeloablative haematopoietic stem-cell transplantation compared with pulse cyclophosphamide once per month for systemic sclerosis (ASSIST): an open-label, randomized phase 2 trial. Lancet. 2011;378(9790):498–506.
15. van Larr JM, Farge D, Sont JK, et al. Autologous hematopoietic stem cell transplantation versus intravenous pulse cyclophosphamide in diffuse cutaneous systemic sclerosis: a randomized clinical trial.JAMA.2014;311:2490-8.
16. Naraghi K, van Laar JM. Update on stem cell transplantation for systemic sclerosis: recent trial results. Curr Rheumatol Rep. 2013;15:326
17. Ramaswamy S, Jain S, & Ravindran V. Hematopoietic stem cell transplantation for autoimmune rheumatic diseases. World J Transplant. 2016;6(1):199-205.
18. Kapur SK and Katz AJ. Review of the adipose derived stem cell secretome. Biocheimi. 2013;95:2222-8.
19. Leto Barone AA, Khalifian S, Lee WP, et al. Immunomodulatory effects of adipose-derived stem cells: fact or fiction?. Biomed Res Int. 2013; 2013:383685.
20. Del Papa N, Di Luca G, Sambataro D, et al. Regional implantation of autologous adipose tissue-derived cells induces a prompt healing of long-lasting indolent digital ulcers in patients with systemic sclerosis. Cell Transplant. 2015;24(11):2297-35.
21. Scuderi N, Ceccarelli S, Onesti MG, et al. Human adipose-derived stromal cells for cell-based therapies in the treatment of systemic sclerosis. Cell Transplant. 2013;22:779-95.
22. Granel B, Daumas A, Jouve E, et al. Safety, tolerability and potential efficacy of injection of autologous adipose-derived stromal vascular fraction in the fingers of patients with systemic sclerosis: an open-label phase I trial. Ann Rheum Dis. 2015;74(12):2175-2182.
23. Takagi G, Miyamoto M, Tara S, et al. Therapeutic vascular angiogenesis for intractable macroangiopathy-related digital ulcer in patients with systemic sclerosis: a pilot study Rheumatology (2014) 53 (5): 854-859
24. Song X, Lv HY, Sun LX, et al. Autologous stem cell transplantation for systemic lupus erythematosus: report of efficacy and safety at 7 years of follow-up in 17 patients. Transplant Proc. 2011;43(5):1924–7.
25. Saccardi R, Tyndall A, Coghlan G, et al. Consensus statement concerning cardiotoxicity occurring during haematopoietic stem cell transplantation in the treatment of autoimmune disease, with special reference to systemic sclerosis and multiple sclerosis. Bone Marrow Transplant. 2004;34(10):877–81.
26. ••Snowden JA, Saccardi R, Allez M, et al. Haematopoietic SCT in severe autoimmune diseases: updated guidelines of the European Group for Blood and Marrow Transplantation. Bone Marrow Transplantation. 2012;47:770-90. Most recent society guidelines regarding patient selection and transplant processes for stem cell transplants in autoimmune diseases.
27. van Laar JM, Naraghi K, Tyndall A. Haematopoietic stem cell transplantation for poor-prognosis systemic sclerosis. Rheumatology 2015; 54: 2126–2133.
28. Burt RK, Shah SJ, Gheorghiade M et al.
Hematopoietic stem cell transplantation for systemic sclerosis: if you are confused, remember: “it is a matter of the heart”. Journal of Rheumatology. 2012;39:206–9.
29. Burt RK, Oliveira MC, & Shah SJ. Cardiac Assessment Before Stem Cell Transplantation for Systemic Sclerosis. JAMA. 2014;12(17):1803.
30. N Del Papa, Onida F, Zaccara E, et al. Autologous hematopoietic stem cell transplantation has better outcome than conventional therapies in patients with rapidly progressive systemic sclerosis. Bone Marrow Transplantation. advance online publication 22 August 2016; doi: 10.1038/bmt.2016.211
31. van Laar JM, Naraghi K, & Tyndall A. Haematopoietic stem cell transplantation for poor-prognosis systemic sclerosis. Rheumatology (Oxford). 2015;54(12):2126-33.
32. Blank N, Lisenko K, Pavel P, et al. Low-dose cyclophosphamide effectively mobilizes peripheral blood stem cells in patients with autoimmune disease. Eur J Haematol. 2016;97(1):78-82.
33. Martínez C, Urbano-Ispizua A, Rozman C, et al. Immune reconstitution following allogeneic peripheral blood progenitor cell transplantation: comparison of recipients of positive CD34+ selected grafts with recipients of unmanipulated grafts. Exp Hematol. 1999;27:561–8.
34. Marek A, Stern M, Chalandon Y, et al. The impact of T-cell depletion techniques on the outcome after haploidentical hematopoietic SCT. Bone Marrow Transplant 2014; 49:55–61.
35. Slaper-Cortenbach IC, Wijngaarden-du Bois MJ, de Vries-van Rossen A,, et al. The depletion of T cells from haematopoietic stem cell transplants. Rheumatology (Oxford) 1999;38(8):751–754.
36. Webb IJ, Coral FS, Andersen JW, Elias AD, Finberg RW, et al. Sources and sequelae of bacterial contamination of hematopoietic stem cell components: implications for the safety of hematotherapy and graft engineering. Transfusion. 1996;36(9):782–788.
37. Oliveira MC, Labopin M, Henes J, et al. Does ex vivo CD34+ positive selection influence outcome after autologous hematopoietic stem cell transplantation in systemic sclerosis patients?. Bone Marrow Transplant. 2016;51(4):501.5.
38. Henes JC, Koetter I, Horger M, et al. Autologous stem cell transplantation with thiotepa-based conditioning in patients with systemic sclerosis and cardiac manifestations. Rheumatology (Oxford). 2014;53(5):919-22.
39. Autologous Stem Cell Systemic Sclerosis Immune Suppression Trial (DIScl2011). Available at https://clinicaltrials.gov/show/NCT01445821. Accessed August 2016
40. Craciunescu OI, Steffey BA, Kelsey CR, et al. Renal shielding and dosimetry for patients with severe systemic sclerosis receiving immunoablation with total body irradiation in the scleroderma: cyclophosphamide or transplant trial. Int J Radiat Oncol Biol Phys. 2011;79(4):1248–55.
2. Hu H, Stein-Streilein J. Hapten-immune pulmonary interstitial fibrosis (HIPIF) in mice requires both CD4+ and CD8+ T lymphocytes. J Leukoc Biol. 1993;54(5):414–22.
3. Rosa SB, Voltarelli JC, Chies JA, et al. The use of stem cells for the treatment of autoimmune diseases. Braz J Med Biol Res. 2007;40(12):1579–97.
4. Denton CP. Systemic sclerosis: from pathogenesis to targeted therapy. Clin Exp Rheumatol. 2015;33(4Suppl 92):S3-7.
5. Ioannidis JP, Vlachoyiannopoulos PG, Haidich AB, et al. Mortality in systemic sclerosis: an international meta-analysis of individual patient data. Am J Med.2005;118:2–10
6. Mascarenhas S, Avalos B, & Ardoin SP, An Update on Stem Cell Transplantation in Autoimmune Rheumatologic Disorders. Curr Allergy Asthma Rep. 2012;12(6):530-540.
7. Sykes M & Nikolic B. Treatment of severe autoimmune disease by stem-cell transplantation. Nature.2005;435;620-627.
8. DiPersio JF, Micallef IN, Stiff PJ, et al. Phase III Prospective Randomized Double-Blind Placebo-Controlled Trial of Plerixafor Plus Granulocyte Colony-Stimulating Factor Compared with Placebo Plus Granulocyte Colony-Stimulating Factor for Autologous Stem-Cell Mobilization and Transplantation for Patients with Non-Hodgkin’s Lymphoma. J Clin Oncol. 2009;27(28):4767–73.
9. Moore J, Brooks P, Milliken S, et al. A pilot randomized trial comparing CD34-selected versus unmanipulated hematopoietic stem cell transplantation for severe refractory rheumatoid arthritis. Arthritis Rheum. 2002;46(9):2301–9.
10. Kelsy PJ, Oliveira MC, Badogolio M, et al. Haematopoietic stem cell transplantation in autoimmune diseases: From basic science to clinical practice. Curr Res Transl Med. 2016;64(2):71-82.
11. Nash RA, McSweeney PA, Crofford LJ, et al. High-dose immunosuppressive therapy and autologous hematopoietic cell transplantation for severe systemic sclerosis: long-term follow-up of the US multicenter pilot study. Blood. 2007;110-1388-96
12. Oyama Y, Barr WG, Statkute L, et al. Autologous non-myeloablative hematopoietic stem cell transplantation in patients with systemic sclerosis. Bone Marrow Transplant. 2007;40(6):549-55.
13. Henes JC, Schmalzing M, Vogel W, et al. Optimization of autologous stem cell transplantation for systemic sclerosis: a single-center long-term experience in 26 patients with severe organ manifestations. J Rheumatol. 2012; 39:269–275
14. Burt RK, Shah SJ, Dill K, et al. Autologous non-myeloablative haematopoietic stem-cell transplantation compared with pulse cyclophosphamide once per month for systemic sclerosis (ASSIST): an open-label, randomized phase 2 trial. Lancet. 2011;378(9790):498–506.
15. van Larr JM, Farge D, Sont JK, et al. Autologous hematopoietic stem cell transplantation versus intravenous pulse cyclophosphamide in diffuse cutaneous systemic sclerosis: a randomized clinical trial.JAMA.2014;311:2490-8.
16. Naraghi K, van Laar JM. Update on stem cell transplantation for systemic sclerosis: recent trial results. Curr Rheumatol Rep. 2013;15:326
17. Ramaswamy S, Jain S, & Ravindran V. Hematopoietic stem cell transplantation for autoimmune rheumatic diseases. World J Transplant. 2016;6(1):199-205.
18. Kapur SK and Katz AJ. Review of the adipose derived stem cell secretome. Biocheimi. 2013;95:2222-8.
19. Leto Barone AA, Khalifian S, Lee WP, et al. Immunomodulatory effects of adipose-derived stem cells: fact or fiction?. Biomed Res Int. 2013; 2013:383685.
20. Del Papa N, Di Luca G, Sambataro D, et al. Regional implantation of autologous adipose tissue-derived cells induces a prompt healing of long-lasting indolent digital ulcers in patients with systemic sclerosis. Cell Transplant. 2015;24(11):2297-35.
21. Scuderi N, Ceccarelli S, Onesti MG, et al. Human adipose-derived stromal cells for cell-based therapies in the treatment of systemic sclerosis. Cell Transplant. 2013;22:779-95.
22. Granel B, Daumas A, Jouve E, et al. Safety, tolerability and potential efficacy of injection of autologous adipose-derived stromal vascular fraction in the fingers of patients with systemic sclerosis: an open-label phase I trial. Ann Rheum Dis. 2015;74(12):2175-2182.
23. Takagi G, Miyamoto M, Tara S, et al. Therapeutic vascular angiogenesis for intractable macroangiopathy-related digital ulcer in patients with systemic sclerosis: a pilot study Rheumatology (2014) 53 (5): 854-859
24. Song X, Lv HY, Sun LX, et al. Autologous stem cell transplantation for systemic lupus erythematosus: report of efficacy and safety at 7 years of follow-up in 17 patients. Transplant Proc. 2011;43(5):1924–7.
25. Saccardi R, Tyndall A, Coghlan G, et al. Consensus statement concerning cardiotoxicity occurring during haematopoietic stem cell transplantation in the treatment of autoimmune disease, with special reference to systemic sclerosis and multiple sclerosis. Bone Marrow Transplant. 2004;34(10):877–81.
26. ••Snowden JA, Saccardi R, Allez M, et al. Haematopoietic SCT in severe autoimmune diseases: updated guidelines of the European Group for Blood and Marrow Transplantation. Bone Marrow Transplantation. 2012;47:770-90. Most recent society guidelines regarding patient selection and transplant processes for stem cell transplants in autoimmune diseases.
27. van Laar JM, Naraghi K, Tyndall A. Haematopoietic stem cell transplantation for poor-prognosis systemic sclerosis. Rheumatology 2015; 54: 2126–2133.
28. Burt RK, Shah SJ, Gheorghiade M et al.
Hematopoietic stem cell transplantation for systemic sclerosis: if you are confused, remember: “it is a matter of the heart”. Journal of Rheumatology. 2012;39:206–9.
29. Burt RK, Oliveira MC, & Shah SJ. Cardiac Assessment Before Stem Cell Transplantation for Systemic Sclerosis. JAMA. 2014;12(17):1803.
30. N Del Papa, Onida F, Zaccara E, et al. Autologous hematopoietic stem cell transplantation has better outcome than conventional therapies in patients with rapidly progressive systemic sclerosis. Bone Marrow Transplantation. advance online publication 22 August 2016; doi: 10.1038/bmt.2016.211
31. van Laar JM, Naraghi K, & Tyndall A. Haematopoietic stem cell transplantation for poor-prognosis systemic sclerosis. Rheumatology (Oxford). 2015;54(12):2126-33.
32. Blank N, Lisenko K, Pavel P, et al. Low-dose cyclophosphamide effectively mobilizes peripheral blood stem cells in patients with autoimmune disease. Eur J Haematol. 2016;97(1):78-82.
33. Martínez C, Urbano-Ispizua A, Rozman C, et al. Immune reconstitution following allogeneic peripheral blood progenitor cell transplantation: comparison of recipients of positive CD34+ selected grafts with recipients of unmanipulated grafts. Exp Hematol. 1999;27:561–8.
34. Marek A, Stern M, Chalandon Y, et al. The impact of T-cell depletion techniques on the outcome after haploidentical hematopoietic SCT. Bone Marrow Transplant 2014; 49:55–61.
35. Slaper-Cortenbach IC, Wijngaarden-du Bois MJ, de Vries-van Rossen A,, et al. The depletion of T cells from haematopoietic stem cell transplants. Rheumatology (Oxford) 1999;38(8):751–754.
36. Webb IJ, Coral FS, Andersen JW, Elias AD, Finberg RW, et al. Sources and sequelae of bacterial contamination of hematopoietic stem cell components: implications for the safety of hematotherapy and graft engineering. Transfusion. 1996;36(9):782–788.
37. Oliveira MC, Labopin M, Henes J, et al. Does ex vivo CD34+ positive selection influence outcome after autologous hematopoietic stem cell transplantation in systemic sclerosis patients?. Bone Marrow Transplant. 2016;51(4):501.5.
38. Henes JC, Koetter I, Horger M, et al. Autologous stem cell transplantation with thiotepa-based conditioning in patients with systemic sclerosis and cardiac manifestations. Rheumatology (Oxford). 2014;53(5):919-22.
39. Autologous Stem Cell Systemic Sclerosis Immune Suppression Trial (DIScl2011). Available at https://clinicaltrials.gov/show/NCT01445821. Accessed August 2016
40. Craciunescu OI, Steffey BA, Kelsey CR, et al. Renal shielding and dosimetry for patients with severe systemic sclerosis receiving immunoablation with total body irradiation in the scleroderma: cyclophosphamide or transplant trial. Int J Radiat Oncol Biol Phys. 2011;79(4):1248–55.