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• W2588449766 abstract "Abstract Secondary autoimmune disorders following hematopoietic stem cell transplantation (HSCT) for malignancies occur at a reported frequency of 2 to 5%. Patients undergoing HSCT for autoimmune disorders may however have an added propensity to this complication, given the genetic predisposition to autoimmunity. Therefore, we undertook a retrospective analysis of all patients who underwent an autologous HSCT (auto−HSCT) for an autoimmune disease to determine the occurrence of a second autoimmune disorder, its nature, outcome and risk factors. In all, 154 patients underwent auto−HSCT for various autoimmune diseases in the period from August 1996 to March 2006. The peripheral blood stem cell product was either CD34−selected (n=87) or unmanipulated (n=67), depending on disease−specific protocols. The conditioning regimens consisted of various combinations of cyclophosphamide with either antithymocyte globulin (ATG) or alemtuzumab, or cyclophosphamide with intravenous busulfan or total body irradiation, again depending on disease−specific protocols. The autoimmune diseases represented were systemic lupus erythematosus (SLE) (n=60, 38.9%), systemic sclerosis (SSc) (n=13, 8.4%), multiple sclerosis (MS) (n=42, 27.3 %), rheumatoid arthritis (n=6, 3.9%), Crohn’s disease (n=20, 13.0%) and others (n=13, 8.4%). There were 5 patients (2 with SLE, one each with MS, SLE and SSc) who developed an autoimmune disorder distinct from their underlying autoimmune disease at a median of 5 months (2 to 30 months) after HSCT. The frequency of a secondary autoimmune disease was 3 of 24 among patients receiving alemtuzumab, 2 of 102 among those receiving ATG and none (0 of 28) of those who received neither of these lympho−depleting antibodies (p=0.018). The difference between the frequency of this complication was also significantly higher among those receiving alemtuzumab compared to ATG (p=0.017). The frequency of a secondary autoimmune disease among those who received a CD34−selected graft was 2 of 87 versus 3 of 67 of those who received unselected stem cells (p=0.449). Two patients with SLE who received an ATG−containing conditioning regimen, developed acquired factor VIII inhibitors with severe bleeding. One patient each with MS, SSc and SLE, who received an alemtuzumab−containing conditioning regimen, developed severe autoimmune cytopenias. The 5 patients required multiple immunosuppressants to control the secondary autoimmune disorder. ATG and alemtuzumab induce a protracted post−HSCT lymphopenia, with particularly delayed reconstitution in T cell function. The resultant immune dysregulation in an autoimmune−prone patient may predispose to a second autoimmune disease. The increased likelihood of this complication seen with alemtuzumab recommends against its use in auto−HSCT for autoimmune disease. Conditioning Regimen and Occurrence of Secondary Autoimmune Disease Regimen Patients Treated (n) Primary Autoimmune Disease Secondary Autoimmune Disease/number Cy:Cyclophosphamide; rATG:rabbit antithymocyte globulin; eATG:equine ATG; Al:Alemtuzumab; Bu:IV Busufan; SLE:systemic lupus erythematosus; SSc:systemic sclerosis; CD:Crohn’s disease; MS:multiple sclerosis; RA:rheumatoid arthritis Cy/rATG 51 SLE, SSc, CD, MS, others None Cy/eATG 51 SLE Acquired FVIII inhibitor (n=2) Cy/Al 24 MS, SLE Autoimmune cytopenias (n=3) Cy/TBI 22 MS None Bu/Cy 6 RA None" @default.
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• W2588449766 date "2006-11-16" @default.
• W2588449766 modified "2023-09-28" @default.
• W2588449766 title "Immune Dysregulation after Hematopoietic Stem Cell Transplantation for Autoimmune Diseases Leading to Development of a Second Autoimmune Disorder: Role of Conditioning Regimen Used?." @default.
• W2588449766 doi "https://doi.org/10.1182/blood.v108.11.760.760" @default.
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