isrctn.org Identifier: ISRCTN54371254.

To specify the incidence and risk factors for secondary autoimmune diseases (ADs) after HSCT for a primary AD, we retrospectively analyzed AD patients treated by HSCT reported to EBMT from 1995 to 2009 with at least 1 secondary AD (cases) and those without (controls). After autologous HSCT, 29 of 347 patients developed at least 1 secondary AD within 21.9 (0.6-49) months and after allogeneic HSCT, 3 of 16 patients. The observed secondary ADs included: autoimmune hemolytic anemia (n ‫؍‬ 3), acquired hemophilia (n ‫؍‬ 3), autoimmune thrombocytopenia (n ‫؍‬ 3), antiphospholipid syndrome (n ‫؍‬ 2), thyroiditis (n ‫؍‬ 12), blocking thyroid-stimulating hormone receptor antibody (n ‫؍‬ 1), Graves disease (n ‫؍‬ 2), myasthenia gravis (n ‫؍‬ 1), rheumatoid arthritis (n ‫؍‬ 2), sarcoidosis (n ‫؍‬ 2), vasculitis (n ‫؍‬ 1), psoriasis (n ‫؍‬ 1), and psoriatic arthritis (n ‫؍‬ 1). After autologous HSCT for primary AD, the cumulative incidence of secondary AD was 9.8% ؎ 2% at 5 years. Lupus erythematosus as primary AD, and antithymocyte globulin use plus CD34 ؉ graft selection were important risk factors for secondary AD by multivariate analysis. With a median follow-up of 6.2 (0.54-11) years after autologous HSCT, 26 of 29 patients with secondary AD were alive, 2 died during their secondary AD (antiphospholipid syndrome, hemophilia), and 1 death was HSCT-related. This European multicenter study underlines the need for careful management and follow-up for secondary AD after HSCT. (Blood. 2011;118(6):1693-1698)

Autoimmune hematological diseases (AHDs) may occur after allogeneic hematopoietic stem cell transplantation (HSCT), but reports on these complications in large cohorts of pediatric patients are lacking. Between 1998 and 2011, 1574 consecutive children underwent allogeneic HSCT in 9 Italian centers. Thirty-three children (2.1%) developed AHDs: 15 autoimmune hemolytic anemia (45%), 10 immune thrombocytopenia (30%), 5 Evans' syndrome (15%), 2 pure red cell aplasia (6%), and 1 immune neutropenia (3%). The 10-year cumulative incidence of AHDs was 2.5% (95% confidence interval, 1.7 to 3.6). In a multivariate analysis, the use of alternative donor and nonmalignant disease was statistically associated with AHDs. Most patients with AHDs (64%) did not respond to steroids. Sustained complete remission was achieved in 87% of cases with the anti-CD20 monoclonal antibody (rituximab). Four patients (9%) (1 autoimmune hemolytic anemia, 1 Evans' syndrome, 2 immune thrombocytopenia) died at a median of 87 days after AHD diagnosis as a direct or indirect consequence of their disorder. Our data suggest that AHDs are a relatively rare complication occurring after HSCT that usually respond to treatment with rituximab.

Key Points• Autoimmune diseases do occur after CBT in approximately 5% of patients.• Of these, AIHA or ITP were observed the most often and were treated with prednisone, CSA, and RTX.To describe the incidence, risk factors, and treatment of autoimmune diseases (ADs) occurring after cord blood transplantation (CBT), we analyzed both CBT recipients reported to EUROCORD who had developed at least 1 new AD and those who had not. Fifty-two of 726 reported patients developed at least 1 AD within 212 days (range, 27-4267) after CBT. Cumulative incidence of ADs after CBT was 5.0% ؎ 1% at 1 year and 6.6% ؎ 1% at 5 years. Patients developing ADs were younger and had more nonmalignant diseases (P < .001). ADs target hematopoietic (autoimmune hemolytic anemia, n ‫؍‬ 20; Evans syndrome, n ‫؍‬ 9; autoimmune thrombocytopenia, n ‫؍‬ 11; and immune neutropenia, n ‫؍‬ 1) and other tissues (thyroiditis, n ‫؍‬ 3; psoriasis, n ‫؍‬ 2; Graves disease, n ‫؍‬ 1; membranous glomerulonephritis, n ‫؍‬ 2; rheumatoid arthritis, n ‫؍‬ 1; ulcerative colitis, n ‫؍‬ 1; and systemic lupus erythematosus, n ‫؍‬ 1). Four patients developed 2 ADs (3 cases of immune thrombocytopenia followed by autoimmune hemolytic anemia and 1 Evans syndrome with rheumatoid arthritis). By multivariate analysis, the main risk factor for developing an AD was nonmalignant disease as an indication for CBT (P ‫؍‬ .0001). Hematologic ADs were most often treated with steroids, rituximab, and cyclosporine. With a median follow-up of 26 months (range, 2-91), 6 of 52 patients died as a consequence of ADs. We conclude that CBT may be followed by potentially life-threatening, mainly hematologic ADs. (Blood. 2013;121(6):1059-1064)