Complications and Toxicities Associated with Autologous Stem Cell Transplantation for Severe Autoimmune Diseases: Single Center Experience

Abstract BACKGROUND In the past 20 years, autologous hematopoietic stem cell transplantation (ASCT) has opened new avenues in the treatment of patients with severe, treatment-resistant autoimmune diseases with the aim of resetting the patient's immune system. Over the years, this has led to increased safety and efficacy of the procedure however it is still associated with morbidity and mortality. We evaluated the complications and toxicities associated with ASCT for autoimmune diseases at The Ottawa Hospital. METHODS Using the Ottawa stem cell transplant database, consecutive patients undergoing ASCT for autoimmune diseases were identified between 1999 and 2017. Through retrospective chart review, infectious complications, toxicities, length of hospital stay and survival outcomes were extracted. RESULTS Ninety patients underwent ASCT for an autoimmune disease at The Ottawa Hospital between 1999 and 2017 (median age 35 years, range 19-65 and 61% female). Of the 90 patients transplanted, 75 (83.3%) had a neurologic disease (53 with multiple sclerosis, 8 with myasthenia gravis, 5 with chronic inflammatory demyelinating polyneuropathy, 4 with neuromyelitis optica, and 5 with stiff person syndrome), 10 (11.1%) had a rheumatological disease (7 scleroderma and 3 rheumatoid arthritis), 4 (4.4%) ad Crohn's disease and 1 (1.1%) had immune thrombocytopenia. The median follow-up time in this study was 3.2 years from date of ASCT (range 0-15.75 years). The median length of stay in hospital was 30 days (range 12-215). The median engraftment time was 10 days for neutrophil recovery and 15 days for platelet recovery. The first 100 days following ASCT included 97 episodes of bacterial infections (28-bacteremia, 8-pneumonia, 29-UTI, 9-C. difficile colitis, 5-neutropenic enterocolitis, 12-skin infections, 4-line infections and 2 sinus/pharyngeal infections), 39 viral reactivations or infections (10-CMV, 7-BK, 2-adenovirus, 2-polyomavirus, 6-EBV, 4-HSV, 4-VZV and 4-respiratory viruses), and 7 episodes of fungal infection (4-mucocutaneous candidiasis, 1-candidemia, 1-yeast on urine culture and 1-C. lusitaneae from sputum). There were 9 patients (10%) that developed acute kidney injury, of which 3 recovered without hemodialysis, 1 recovered with temporary hemodialysis, and 2 required permanent hemodialysis. Ten patients (11.1%) developed liver dysfunction, all of which resolved. There were 17 episodes of hemorrhagic cystitis (5-BK, 2-adenovirus, 2-polyoma virus, 1-CMV, 3 tested negative for viruses, and 4 were untested). The 100-day transplant-related mortality was 2.3% and the overall survival plateaued at 93.5% beyond 2 years (95% CI at 2 years 84.9-97.2%). Two patients developed a secondary malignancy (metastatic adenocarcinoma in a scleroderma patient and acute leukemia in a multiple sclerosis patient that had received mitoxantrone). Five patients have died; 4 from organ toxicity (pulmonary hemorrhage at day -3 in a scleroderma patient, veno-occlusive disease at day 62 in a multiple sclerosis patient, heart failure at day 116 in a scleroderma patient, and bronchiolitis obliterans at day 415 in a neuromyelitis optica patient) and 1 from metastatic adenocarcinoma and advanced scleroderma. CONCLUSION This study confirms that the morbidity and mortality of ASCT for patients with autoimmune disease is similar to that for other patient groups undergoing ASCT. Patient selection should take this into consideration. Disclosures No relevant conflicts of interest to declare.