Allogeneic HSCT for Autoimmune Diseases: A Retrospective Study From the EBMT ADWP, IEWP, and PDWP Working Parties

Abstract

Background: This retrospective study assessed the use and long-term outcome of allogeneic hematopoietic stem cell transplantation (HSCT) in patients with severe autoimmune diseases (ADs), reported to the European Society for Blood and Marrow Transplantation (EBMT) registry. Methods: Between 1997 and 2014, 128 patients received allogeneic HSCT for various hematological ( n = 49) and non-hematological ( n = 79) refractory ADs. The median age was 12.7 years (0.2–62.2). Donors were syngeneic for seven, matched related for 46, unrelated for 51, haploidentical for 15, and cord blood for nine patients. Results: The incidence of grades II-IV acute graft-vs.-host disease (GvHD) was 20.8% at 100 days. Cumulative incidence of chronic GvHD was 27.8% at 5-years. Non-relapse mortality (NRM) was 12.7% at 100-days. Overall survival (OS) and Progression-Free Survival (PFS) were 70.2 and 59.4% at 5-years, respectively. By multivariate analysis, age <18 years, males, and more recent year of transplant were found to be significantly associated with improved PFS. Reduced conditioning intensity was associated with a lower NRM. On a subgroup of 64 patients with detailed information a complete clinical response was obtained in 67% of patients at 1-year. Conclusions: This large EBMT survey suggests the potential of allogeneic HSCT to induce long-term disease control in a large proportion of refractory ADs, with acceptable toxicities and NRM, especially in younger patients.

Hematopoietic Cell Transplantation in Patients With Primary Immune Regulatory Disorders (PIRD): A Primary Immune Deficiency Treatment Consortium (PIDTC) Survey

“…The study illustrates that HCT can be effective for patients with PIRD; resolution of disease symptoms occurred in at least a portion of the patients across most disease groups, but overall long-term survival remained poor (67% at 5-years) with a large portion of deaths occurring in the first 2 years of life. The survival found in this cohort is similar to that recently published for HCT in a broad spectrum of autoimmune and autoinflammatory diseases from European centers (70% at 5-years) (17). Both studies gathered retrospective data spanning a broad timeframe where there has been significant advances in conditioning regimen, targeted immune modulatory therapies for GVHD, and supportive care.…”

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)

“…Likewise, the numbers of patients who have received allo-HSCT for neurological ADs are low [21], even in a recent EBMT analysis of allo-HSCT [24].…”

“…Allogeneic HSCT represents an attractive option for patients with refractory ADs, offering the advantage of complete eradication of autoreactive cells combined with the regeneration of a healthy immune system tolerant to autoantigens. However, because of its significantly higher level of NRM risk, allo-HSCT has rarely been used in the treatment of ADs [21,24,26,128]. Only anecdotal data are available to date for allo-HSCT in neuroinflammatory ADs, notably severe NMO, where sustained clinical benefit with resolution of detectable anti-AQP-4Ab has been reported [129].…”

Prospects of the Use of Cell Therapy to Induce Immune Tolerance

“…Encouragingly, a method for long-term ex vivo HSC expansion has been developed recently (48) that might make homogeneous HSCT easier. Moreover, some patients might develop disease flares resulting from the re-induction of autoimmunity driven by genetic predisposition, and allogeneic HSCT could be used as an alternative therapy (49). The further development of more effective and safer HSCT methods remains the next challenge in cell therapy so that this approach can be used more widely in the future for patients with ADs.…”