Clinical stem cell therapies for severe autoimmune diseases

In the past 5 years approximately 500 patients worldwide suffering from severe autoimmune disease (AD) have received an autologous hematopoietic stem cell transplantation (HSCT) as treatment following high-dose chemotherapy. The EBMT and EULAR data base contains 370 registrations, the most frequently transplanted ADs being multiple sclerosis (MS), systemic sclerosis (SSc), rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), systemic lupus erythematosus (SLE) and idiopathic thrombocytopenic purpura (ITP). Around 70% responded initially well, with durable remission/stabilization seen more frequently in MS and SSc than in RA and SLE, the latter having around 2/3 relapses, the majority of which respond to simple agents. Overall 8% transplant-related mortality was seen with large inter AD differences (12.5% in SSc and only one patient in RA) probably reflecting the degree of vital organ involvement at the time of transplant. This phase I/II data has led to a running phase III randomized trial in SSc called the Autologous Stem cell Transplantation International Scleroderma (ASTIS) trial, and it will soon begin in MS (ASTIMS) and RA (ASTIRA). The concept of immunological "re-setting" has evolved, and needs to be confirmed by longer follow-up and the multicentre, international phase III randomized studies.

Resetting the immune system in refractory Crohn’s disease: Is autologous hematopoietic stem cell transplantation the way forward?

Preparing for Growth: Current Capacity and Challenges in Hematopoietic Stem Cell Transplantation Programs

The Impact of Pre-Transplant Depression on Outcomes of Allogeneic and Autologous Hematopoietic Stem Cell Transplantation

Autologous Hematopoietic Stem Cell Transplantation (HSCT) for Autoimmune Diseases: 10 Years Experience from the European Group for Blood and Marrow Transplantation (EBMT) Working Party on Autoimmune Diseases

Autologous Hematopoietic Stem Cell Transplantation (HCT) is a Safe and Effective Treatment for Primary Plasma Cell Leukemia: The CIBMTR Experience.

Osteochondroma after Hematopoietic Stem Cell Transplantation in Childhood. An Italian Study on Behalf of the AIEOP-HSCT Group

Outcome of relapsed/refractory acute promyelocytic leukaemia in children, adolescents and young adult patients - a 25-year Italian experience.

Serological Response Following BNT162b2 Anti-Sars-Cov-2 mRNA Vaccination in Hematopoietic Stem Cell Transplantation Patients

Role of Hematopoietic Stem Cell Transplantation As Salvage Treatment of Acute Promyelocytic Leukemia Initially Treated with All-Trans-Retinoic Acid: A Retrospective Analysis of the Japan Adult Leukemia Study Group (JALSG) APL97 Study

Incidence and Risk Factors for Secondary Autoimmune Diseases (AD) After Hematopoietic Stem Cell Transplantation (HSCT) for a Severe Autoimmune Disease-A Retrospective EBMT WP AD Study

High-dose immunosuppressive therapy and autologous hematopoietic stem cell transplantation (HSCT) have shown efficacy in systemic sclerosis in phase 1 and small phase 2 trials. To compare efficacy and safety of HSCT vs 12 successive monthly intravenous pulses of cyclophosphamide. The Autologous Stem Cell Transplantation International Scleroderma (ASTIS) trial, a phase 3, multicenter, randomized (1:1), open-label, parallel-group, clinical trial conducted in 10 countries at 29 centers with access to a European Group for Blood and Marrow Transplantation-registered transplant facility. From March 2001 to October 2009, 156 patients with early diffuse cutaneous systemic sclerosis were recruited and followed up until October 31, 2013. HSCT vs intravenous pulse cyclophosphamide. The primary end point was event-free survival, defined as time from randomization until the occurrence of death or persistent major organ failure. A total of 156 patients were randomly assigned to receive HSCT (n = 79) or cyclophosphamide (n = 77). During a median follow-up of 5.8 years, 53 events occurred: 22 in the HSCT group (19 deaths and 3 irreversible organ failures) and 31 in the control group (23 deaths and 8 irreversible organ failures). During the first year, there were more events in the HSCT group (13 events [16.5%], including 8 treatment-related deaths) than in the control group (8 events [10.4%], with no treatment-related deaths). At 2 years, 14 events (17.7%) had occurred cumulatively in the HSCT group vs 14 events (18.2%) in the control group; at 4 years, 15 events (19%) had occurred cumulatively in the HSCT group vs 20 events (26%) in the control group. Time-varying hazard ratios (modeled with treatment × time interaction) for event-free survival were 0.35 (95% CI, 0.16-0.74) at 2 years and 0.34 (95% CI, 0.16-0.74) at 4 years. Among patients with early diffuse cutaneous systemic sclerosis, HSCT was associated with increased treatment-related mortality in the first year after treatment. However, HCST conferred a significant long-term event-free survival benefit. isrctn.org Identifier: ISRCTN54371254.

Autologous Hematopoietic Stem Cell Transplantation (AHSCT) in Severe Auto-Immune Disease Adult Patients: Analysis of Outcomes from the French Society for Bone Marrow Transplantation and Cellular Therapy (SFGMT-TC) in Light of the European Society for Blood and Marrow Transplantation (EBMT) Activity

Evolution, trends, outcomes, and economics of hematopoietic stem cell transplantation in severe autoimmune diseases.

The optimal treatment strategy with the use of hematopoietic stem cell transplantation (HSCT) for relapsed and refractory Hodgkin lymphoma (HL) remains unclear. We performed a retrospective analysis using registry data from the Japanese Society for Hematopoietic Cell Transplantation. Adult patients with HL who underwent a first autologous or a first allogeneic HSCT between 2002 and 2009 were included. Patients who underwent HSCT in first complete remission (CR) were excluded. Autologous and allogeneic HSCT were performed in 298 and 122 patients, respectively. For autologous HSCT, overall survival at 3 years (3yOS) was 70%, and sex, age, disease status, and performance status (PS) at HSCT were prognostic factors. OS was favorable even in patients who underwent autologous HSCT in disease status other than CR. For allogeneic HSCT, 3yOS was 43%, and sex and PS at HSCT were prognostic factors. Disease status at HSCT, previous autologous HSCT, and conditioning intensity did not affect OS. Moreover, graft-versus-host disease did not affect progression-free survival or relapse/progression rate. A first allogeneic HSCT without a previous autologous HSCT was performed in 40 patients. 3yOS was 45%, and was significantly inferior to that in patients who underwent their first autologous HSCT. This result was retained after the correction by the different patient characteristics according to the type of HSCT. In conclusion, autologous HSCT is effective in prolonging survival in patients with relapsed and refractory HL. Allogeneic HSCT might be beneficial even to relapsed HL after autologous HSCT, although establishing the role of allogeneic HSCT remains a challenge.