A Two Step Approach to Autologous Peripheral Blood Stem Cell Transplantation for Refractory Chronic Inflammatory Bowel Diseases – Results of a Pilot Study

Abstract

Introduction: In about 5% chronic inflammatory bowel diseases (IBD) are refractory to current medical or surgical treatment. Ubiquitous bacterial antigens are supposed to trigger an uncontrolled immune reaction in IBD based on a genetic predisposition. Therefore it is intriguing to try to eliminate the disturbed immune reactions and to redevelop a better immunological tolerance. Methods: We used a two step approach towards autologous peripheral blood stem cell transplantation (aPBSCT) in patients with IBD refractory to corticosteroids, aminosalicylates, immunosuppressors, antibiotics and Infliximab. Remission is induced with cyclophosphamide (2.0g/m2/d on two successive days), and peripheral blood stem cells are harvested. In case of relapse despite maintenance therapy aPBSCT can be performed after high-dose cyclophosphamide (50mg/kg bw/d on four successive days). Results: 6 patients were included in this pilot study. In the two patients with severe ulcerative colitis stem cell mobilisation therapy induced a response. In one patient colectomy was performed for safety reasons, in the other one due to relapse. In all 4 patients with Crohn’s disease (CD) mobilisation chemotherapy induced an endoscopical and clinical remission. Two have a heterozygous mutation of the NOD–2-gene (3020insC-mutation, C2104T mutation). In one of them, there was an early relapse in the terminal ileum. Resection was performed followed by maintenance therapy with budesonide. In the other patient with involvement of the total colon, after complete remission there is a beginning relapse in the sigmoid colon, which will be resected. Two CD patients have no mutation of the NOD–2-gene. In one patient with refractory Crohn’s colitis, mobilisation therapy induced a complete remission since 12 months on low dose methylprednisolone and thioguanine. In one patient with CD and multiple relapses after subtotal colectomy mobilisation chemotherapy followed by aPBSCT ultimately led to a complete disappearance of the disease, which lasts three years until now. Conclusions: Stem cell mobilisation chemotherapy with cyclophosphamide induces a remission in refractory IBD. High-dose cyclophosphamide followed by aPBSCT may be a beneficial new option for selected patients with refractory Crohn’s disease.