Haematopoietic stem cell transplantation for severe autoimmune diseases in children: A review of current literature, registry activity and future directions on behalf of the autoimmune diseases and paediatric diseases working parties of the European Society for Blood and Marrow Transplantation

Abstract

Although modern clinical management strategies have improved the outcome of paediatric patients with severe autoimmune and inflammatory diseases over recent decades, a proportion will experience ongoing or recurrent/relapsing disease activity despite multiple therapies often leading to irreversible organ damage, and compromised quality of life, growth/development and long-term survival. Autologous and allogeneic haematopoietic stem cell transplantation (HSCT) have been used successfully to induce disease control and often apparent cure of severe treatment-refractory autoimmune diseases (ADs) in children. However, transplant-related outcomes are disease-dependent and long-term outcome data are limited in respect to efficacy and safety. Moreover, balancing risks of HSCT against AD prognosis with continually evolving non-transplant options is challenging. This review appraises published literature on HSCT strategies and outcomes in individual paediatric ADs. We also provide a summary of the European Society for Blood and Marrow Transplantation (EBMT) Registry, where 343 HSCT procedures (176 autologous and 167 allogeneic) have been reported in 326 children (<18 years) for a range of AD indications. HSCT is a promising treatment modality, with potential long-term disease control or cure, but therapy-related morbidity and mortality need to be reduced. Further research is warranted to establish the position of HSCT in paediatric ADs via registries and prospective clinical studies to support evidence-based interspeciality guidelines and recommendations. K E Y W O R D S autoimmune diseases, haematopoietic stem cell transplantation, paediatric Selim Corbacioglu and Raffaella Greco contributed equally.

Autologous haematopoiesis stem cell transplantation (AHSCT) for treatment-refractory autoimmune diseases in children

“…The EBMT registry has documented 16 paediatric cases of progressive, treatment-resistant SSc since 1999 including limited disease course and outcome data. 22 In 2004, a European study of 57 patients with SSc included five children. Overall, most patients had a favourable response to AHSCT.…”

Patient-reported outcomes in HSCT for autoimmune diseases: Considerations on behalf of the EBMT ADWP, PAC, and Nurses Group

“… 1 In addition, with the increasing recognition of genetic risk variants contributing to the development of certain AIDs, it has become evident that allogeneic rather than autologous HSCT could be a promising approach for long-term disease control, particularly when there is overlap with autoinflammatory and immunodeficiency diseases in the pediatric setting. 7 , 8 A careful and multidisciplinary appraisal of potential benefits and risks by disease and transplant specialists, working closely together in a multidisciplinary team with patients and carers, is strongly recommended to determine individual suitability for HSCT. 9 …”