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

Retrospective analysis of AD pts treated by HSCT as reported to the EBMT data management system ProMISe until November 2009. Each EBMT participating centre was asked to identify all pts having developed at least one AD and those not having developed AD after HSCT as controls with complete detailed information on HSCT and outcome of original disease and treatment and outcome of secondary AD for cases. Cumulative incidence curves were used to estimate incidence of AD considering death as a competing event. Associations of patients and graft characteristics with secondary AD were evaluated by multivariate analyses, using Cox proportional hazards. All tests were two-sided. The type I error rate was fixed at 0.05 to determinate factors associated with time to event outcomes.

Out of 338 patients from 26 centres in 12 European countries, 33 developed at least one secondary AD within 569 (19-1489) days after HSCT, 305 pts without secondary AD served as controls. Characteristics of both groups are in table 1. The cumulative incidence of secondary AD after HSCT for primary AD was 6.5 (±1) % after 3 years and 11.1 (±2) % after 5 years. Diagnoses of secondary AD were thyroiditis (n=13), autoimmune hemolytic anemia (AIHA) (n=4), autoimmune thrombopenia (n=3), acquired hemophilia (n=3), Graves' disease, rheumatoid arthritis, sarcoidosis, antiphospholipid syndrome and psoriatic arthritis in 2 pts each and myasthenia gravis and vasculitis in 1 pt each. Two pts developed two secondary AD. After multivariate analysis age younger than 33 years p=0.016 (overall median age at HSCT), primary systemic lupus erythematosus (SLE) p= 0.003, ex vivo manipulation p= 0.015 and HSCT performed after the year 2002 p=0.02 remained as risk factors for secondary AD. At last follow-up within 5.9 years (0.25-15 years) after HSCT, 28/33 pts with secondary AD were alive and 257/305 nonAD pts. 0ne Systemic Sclerosis pt and one Multiple Sclerosis transplanted pt died from secondary embolic antiphospholipid syndrome and acquired hemophilia respectively. 26 primary AD pts received specific therapy after HSCT for their secondary AD. The pts with acquired hemophilia received steroids plus cyclophosphamide and additional Rituximab or ivIG or plasmapheresis, those with immune thrombocytopenia responded to steroids. One pt with thrombocytopenia followed by AIHA needed additional immunosuppression and Rituximab. Two pts with AIHA received steroids, cyclophosphamide and additional Rituximab, and one case also ivIG and ultimately allogeneic HSCT for secondary AID.

At last follow-up, 12 pts remained in remission of secondary AD without treatment, 15 pts needed ongoing therapy, 3 pts had persistent secondary AD without therapy.

This first multicenter study after HSCT for primary AD showed that secondary AD occurred in 10% of 338 pts after HSCT and led to death in 2 pts. Younger age and SLE as primary AD were significant risk factors for secondary AD, but contrary to previous single centre US experience, conditioning with ATG or alemtuzumab did not increase the secondary AD risk. Secondary AD after HSCT should be added to the post transplant follow up clinical parameters.

Lenhoff: Celgene: Honoraria.