Hematopoietic cell transplantation (HCT) has been evaluated as a treatment option for patients with autoimmune diseases (ADs) that respond poorly to conventional immunosuppressive treatments and supportive care. However, HCT use varies widely based on geography and disease type.
In an analysis of data from the European Society for Blood and Marrow Transplantation (EBMT) registry, John A. Snowden, MBChB, MD, from the Department of Hematology at the Sheffield Teaching Hospitals National Health Service Foundation Trust in the United Kingdom, and co-authors assessed trends and outcomes associated with HCT for a variety of ADs. They found that center experience, accreditation, and a country’s socioeconomic status are related to HCT outcomes.
The findings “confirm that [use of] HCT for severe ADs is sustained and increasing, despite the introduction and widespread adoption of biologic and other modern therapies,” wrote Dr. Snowden about the study published in Blood Advances.
EBMT is a not-for-profit society representing more than 600 HCT centers in Europe and other areas, and the registry includes data on more than 2,000 patients over the course of more than 20 years. Since 1994, 247 centers in 40 countries have reported data on HCT in this setting.
The researchers analyzed data from 1,951 patients with ADs undergoing their first autologous HCT (AHCT; median age = 37 years; range = 3-76 years) or allogeneic HCT (alloHCT; median age = 12 years; range = <1-62 years) between January 1994 and December 2015. Most HCT activity (74%) took place in Italy, Germany, Sweden, the United Kingdom, the Netherlands, Spain, France, and Australia.
Reasons for undergoing HCT included multiple sclerosis (MS; n=839), connective tissue disorders (n=596), inflammatory arthritis (IA; n=178), vasculitis (n=46), inflammatory bowel disease (n=191), hematologic immune cytopenia (n=97), and type 1 diabetes (n=20).
There were two peaks of activity, the authors reported: one in 1999 when IA was the most common indication and then a “gradual upward trend” from 2006 to 2015 as MS, systemic sclerosis, and Crohn’s disease became the most common indications.
The national transplant rates between 2010 and 2015 varied substantially among participating countries, and they correlated with countries’ socioeconomic status, per the Human Development Index (a measurement evaluating a country’s achievements in longevity, knowledge, and standard of living; p=0.006). However, there was no significant association between transplant rates and the Health Care Expenditure (HCE; the total annual consumption of health goods and services plus capital investment in health-care infrastructure; p=0.2) or team density (the number of transplant teams divided by the population; p=0.2).
After a median follow-up of 34 months (range = 1-234 months), the global three- and five-year overall survival (OS) rates for the 1,839 patients undergoing AHCT were 89 percent and 86 percent, respectively, and three- and five-year progression-free survival (PFS) rates were 57 percent and 49 percent.
Relapse incidence (RI) rates at three and five years were 38 percent and 46 percent, and non-relapse mortality (NRM) rates were 4.6 percent and 5.3 percent.
“In support of a learning and experiential curve, there was significant improvement in NRM along with PFS and relapse rate [across time periods],” the authors reported (see TABLE). Several other factors were associated with better PFS outcomes, including AHCT performed for the most common indications (MS, systemic sclerosis, and Crohn’s disease; p=0.001), younger patient age (p=0.001), greater center experience (defined as ≥23 transplants conducted for specific AD; p=0.001), longer center learning (defined as time from first HCT for AD ≥6 years; p=0.01), and JACIE (the Joint Accreditation Committee of the International Society for Cellular Therapy and EBMT) accreditation status (p=0.02).
“Economic factors may influence outcome,” the researchers added: In a univariate analysis of patients with MS and systemic sclerosis, AHCT performed in countries with lower HCE was associated with increased risk of NRM and inferior PFS rates. “Such association of economic factors with outcome in the field of ADs requires further investigation.”
Though there were limited data on patients undergoing alloHCT, long-term outcomes showed global three- and five-year OS rates of 67 percent and 64 percent, respectively, PFS rates of 59 percent and 56 percent, and RI rates of 21 percent and 24 percent. NRM rates rose from 13 percent at 100 days, then plateaued at 20 percent at three and five years. As with AHCT, outcomes appeared to improve over subsequent time periods. Better relapse outcomes were observed in patients younger than 18 years (p=0.002), but no effect was observed with regard to center experience (defined as ≥2 patients).
“The future of HCT in ADs very much depends on the ‘dynamic’ with alternative treatment options, including the new biologic agents,” the researchers concluded. “Moving forward, there is now a strong argument for a focus on ‘implementation science’ to methodically drive the field of HCT for AD into routine, fully funded, high-quality clinical practice, across [specialties].” They added, though, that HCT for ADs is likely to be more resource-intensive than standard HCT, which may slow its uptake.
The study is limited by its retrospective design and reliance on information from a registry database.
Dr. Snowden reports receiving funding from Sanofi and Jazz Pharmaceuticals.
Snowden JA, Badoglio M, Labopin M, et al. Evolution, trends, outcomes and economics of haematopoietic stem cell transplantation in severe autoimmune diseases. Blood Advances. 2017 December 20.