Incidence and Risk Factors for Secondary Autoimmune Diseases (AD) After Cord Blood Transplantation (CBT). Retrospective Analysis on Behalf of Eurocord and the EBMT Autoimmune Diseases Working Party.
Authors: Daikeler Thomas , Labopin Myriam , Socié Gérard , Faraci Maura , Abdel-Rahman Fawzi , Yesilipek M. Akif , Arcese William , O'Meara Anne , Sirvent Anne , Voswinkel Jan , Verdeguer Amparo , Gandemer Virginie , Schoemans Hélène , Cant Andrew J. , Messina Chiara , Sedlacek Petr , Vora Ajay J. , Mialou Valerie , Díez Jose Luis , Sorà Federica , Jubert Charlotte , Herr Andrée-Laure , Ruggeri Annalisa , Crotta Alessandro , Gluckman Eliane , Farge Dominique , Rocha Vanderson 
Published: October 2019

Abstract
Abstract 3460
Autoimmune diseases (AD) have been reported after haematopoetic stem cell transplantation (HSCT) and most commonly autoimmune cytopenias (AIC) are observed. Proposed risk factors are unrelated donor HSCT and presence of chronic graft-versus-host disease (GVHD). Use of CB cells is increasing as an alternative source of adults HSC for allotransplant however incidence and risk factors of AD after CBT have not been described. Since CB lymphocytes are immature and most of the CBT are HLA mismatched, we hypothesize a high incidence and diversity of secondary AD and. Therefore, we conducted a retrospective study in order to describe incidence, nature and risk factors for secondary AD after CBT. We include CBT recipients reported to EUROCORD up to December 2008. All centres were asked to participate to the survey even if they did not observe any case of AD after CBT. For those with AD, detailed information on diagnosis, treatment and outcome were asked. Median follow-up was 44 months (3.2-217). 42 out of 651 patients (pts) from 35 centres had developed at least one secondary AD at a median of 198 days (27-4267) after CBT. The remaining 609 pts without secondary AD served as control group (nonAD). Characteristics of both groups are given in table 1. Cumulative incidence of secondary AD after CBT was 5±1% after 3 years and 6.5±1% after 10 years. Diagnosis of secondary AD were autoimmune haemolytic anemia (AIHA) in 16, autoimmune thrombopenia (ITP) in 9, EVANS syndrome in 6, autoimmune thyroiditis in 3, glomerulonephritis in 2, Graves disease, psoriasis, psoriasis arthritis, immune neutropenia, ulcerative colitis and vasculitis in 1 patient each. Three pts developed ITP followed by AIHA. Median time to develop a AIC was 180 days (27-4267) and non-hematological AD was 322 days (70-1117), respectively (p=0.13). At onset of AD, 3 pts had acute GvHD, 6 chronic GvHD and in 10 pts an infection. In multivariate analysis adjusted for differences between the two groups, the following factors were associated with higher incidence of secondary AD: 1) age<10 years (8.8% vs 3.6%, HR:2.5; p=0.01); 2) CBT after 2006 (8.5% vs 3.4%, HR:2.23; p=0.01) and 3) non-malignant haematological disorders (12.5% vs 4.2%, HR 2.5, p=0.008). There was a trend of higher incidence of AD after unrelated compared to related CBT (6.7% vs 1.6%, HR: 3.71, p=0.07). Number of HLA disparities, cell dose, single or double CBT or use of ATG were not associated with incidence of AD. At last assessment, 317 of overall 651 pts and 35 of 42 pts with secondary AD were alive, respectively. Of 32 pts with AIC, all received immunosuppression as first line therapy (systemic steroids associated or not to CsA, cyclophosphamide) and in 14 ptsrituximab was added. Of those 14 pts receiving anti-CD20, 8 had a complete remission (CR), 3 a partial remission (PR) and 3 did not respond (died due to haemorrhage or infection associated to AIC). Of the 18 remainders 9 had a CR, 5 a PR and 4 did not respond (1 died). Among 6 patients without CR to first line treatment with rituximab, 1 responded to a second line with rituximab, 2 were alive after a different treatment and 3 died. Twenty-five patients with AIC were alive at last follow-up. Of 10 patients with other AD (non AIC), 7 were treated with immunosuppressive treatment (systemic steroids, CsA, tacrolimus), 2 with replacement therapy (thyroid hormone) and 1 treatment was not given (Graves disease); of those 9 patients treated, 7 achieved a CR and 2 a PR. All pts with non-AIC were alive at last follow-up. In conclusion, AD occur in more than 6% of 651 pts after CBT. Most often AIC (n=32) was diagnosed and it is associated with morbidity and mortality (7 pts died of 32). Younger age at transplantation and CBT for non-malignant disease are important risk factors for secondary AD.
Table 1: Characteristics of pts developing AD or not (nonAD) Pts characteristics AD pts nonAD pts P female sex 36% 45% age at HSCT 2.23 (0.2–43.24) years 10.7 (0.11–66.5) years 0.0001 year of HSCT 2006 (95–08) 2006 (92–08) 0.04 Type of donor unrelated 95% 90% 0.26 Indication for HSCT (n) ALL 10 184 AML 2 150 MDS 4 67 AA 5 52 SCID 6 51 CML 3 24 NHL 0 21 Hemoglobinopathy 0 15 Histiocytosis 2 14 Metabolic diseases 9 19 others 1 11 Graft Single cord 85% 77% 0.25 Double cord 14% 23% HLA compatibility 5/6+6/6 68% 48% 0.02 Conditioning RIC 80% 73% 0.34 TBI 20% 43% 0.0004 Serotherapy 73% 74% 0.86 Host CMV status positive 45% 58% 0.11

Disclosures:
No relevant conflicts of interest to declare.