Hematopoietic Stem Cell Transplantation for Systemic Sclerosis: Review of Current Status
Three prospective controlled clinical trials and numerous small series and case reports have confirmed that durable, drug-free remission in systemic sclerosis is possible via an autologous hematopoietic stem cell transplantation. Similar results have been seen in other autoimmune diseases. The exact mechanism by which this immune “reset” was achieved in some but not all cases remains elusive, but includes major reduction of autoreactive immune competent cells, re-establishment of T- and B cell regulatory networks and normalization of tissue niche function, particularly vascular. Some aspects regarding mobilization, conditioning and graft manipulation still remain open, but clearly a significant toxicity is associated with all effective regimens at present, and therefore patient selection remains a key issue. In the hematology/oncology arena, major efforts are being made to reduce genotoxic and other collateral toxicity induced by current mobilization and conditioning protocols, which may also translate to autoimmune disease. These include developments in rapid mobilization and antibody drug conjugate conditioning technology. If effective, such low-toxicity regimens might be applied to autoimmune disease at an earlier stage before chronicity of autoimmunity has been established, thus changing the therapeutic paradigm.
Compliance with Ethical Standards
There was no funding associated with the preparation of this review.
Conflict of interest
AT is a co-founder and shareholder of Magenta Therapeutics.
- 4.Sullivan KM, Furst DE. The evolving role of blood and marrow transplantation for the treatment of autoimmune diseases. J Rheumatol Suppl. 1997;48:1–4.Google Scholar
- 5.Tyndall A, Gratwohl A. Blood and marrow stem cell transplants in auto-immune 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;19:643–5.CrossRefGoogle Scholar
- 6.Lowenthal RM, Cohen ML, Atkinson K, Biggs JC. Apparent cure of rheumatoid arthritis by bone marrow transplantation. J Rheumatol. 1993;20:137–40.Google Scholar
- 9.Knaan-Shanzer S, Houben P, Kinwel-Bohré EP, van Bekkum DW. Remission induction of adjuvant arthritis in rats by total body irradiation and autologous bone marrow transplantation. Bone Marrow Transplant. 1991;8:333–8.Google Scholar
- 15.Burt RK, Shah SJ, 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 Lond Engl. 2011;378:498–506.CrossRefGoogle Scholar
- 16.Burt RK, Balabanov R, Burman J, Sharrack B, Snowden JA, Oliveira MC, et al. Effect of nonmyeloablative hematopoietic stem cell transplantation vs continued disease-modifying therapy on disease progression in patients with relapsing-remitting multiple sclerosis: a randomized clinical trial. JAMA. 2019;321:165–74.CrossRefGoogle Scholar
- 17.Tyndall A. Hematopoietic stem cell transplantation for autoimmune diseases: more than just prolonged immunosuppression. Curr Opin Hematol. 2018;25:433–40.Google Scholar
- 24.Jessop H, Farge D, Saccardi R, Alexander T, Rovira M, Sharrack B, et al. General information for patients and carers considering haematopoietic stem cell transplantation (HSCT) for severe autoimmune diseases (ADs): a position statement from the EBMT Autoimmune Diseases Working Party (ADWP), the EBMT Nurses Group, the EBMT Patient, Family and Donor Committee and the Joint Accreditation Committee of ISCT and EBMT (JACIE). Bone Marrow Transplant. 2019. https://doi.org/10.1038/s41409-019-0430-7.Google Scholar
- 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 Lond Engl. 2013;381:1116–24.CrossRefGoogle Scholar
- 29.Farge D, Burt RK, Oliveira M-C, 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;52:1495–503.CrossRefGoogle Scholar
- 36.Forbes A, Marie I. Gastrointestinal complications: the most frequent internal complications of systemic sclerosis. Rheumatol Oxf Engl. 2009;48(Suppl 3):36–9.Google Scholar
- 44.Alexander T, Thiel A, Rosen O, Massenkeil G, Sattler A, Kohler S, et al. Depletion of autoreactive immunologic memory followed by autologous hematopoietic stem cell transplantation in patients with refractory SLE induces long-term remission through de novo generation of a juvenile and tolerant immune system. Blood. 2009;113:214–23.CrossRefGoogle Scholar
- 59.Minier T, Guiducci S, Bellando-Randone S, Bruni C, Lepri G, Czirják L, et al. Preliminary analysis of the very early diagnosis of systemic sclerosis (VEDOSS) EUSTAR multicentre study: evidence for puffy fingers as a pivotal sign for suspicion of systemic sclerosis. Ann Rheum Dis. 2014;73:2087–93.CrossRefGoogle Scholar
- 61.van den Hombergh WMT, Kersten BE, Knaapen-Hans HKA, Thurlings RM, van der Kraan PM, van den Hoogen FHJ, et al. Hit hard and early: analysing the effects of high-dose methylprednisolone on nailfold capillary changes and biomarkers in very early systemic sclerosis: study protocol for a 12-week randomised controlled trial. Trials. 2018;19:449.CrossRefGoogle Scholar
- 64.Birrer MJ, Moore KN, Betella I, Bates RC. Antibody-drug conjugate-based therapeutics: state of the science. J Natl Cancer Inst. 2019;11:djz035.Google Scholar
- 66.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 J Am Soc Blood Marrow Transplant. 2018;24:1961–4.CrossRefGoogle Scholar