Autologous non-myeloablative haemopoietic stem cell transplantation in relapsing-remitting multiple sclerosis: a phase I/II study

• Published in: Lancet neurology 2009-03, Vol.8 (3), p.244-253
• Main Authors: Burt, Richard K, MD, Loh, Yvonne, MD, Cohen, Bruce, MD, Stefosky, Dusan, MD, Balabanov, Roumen, MD, Katsamakis, George, MD, Oyama, Yu, MD, Russell, Eric J, MD, Stern, Jessica, MD, Muraro, Paolo, MD, Rose, John, MD, Testori, Alessandro, MD, Bucha, Jurate, MD, Jovanovic, Borko, PhD, Milanetti, Francesca, MD, Storek, Jan, MD, Voltarelli, Julio C, MD, Burns, William H, MD
• Format: Article
• Language: English
• Subjects: Adult; Alemtuzumab; Animals; Antibodies, Monoclonal - therapeutic use; Antibodies, Monoclonal, Humanized; Antibodies, Neoplasm - therapeutic use; Antilymphocyte serum; Antilymphocyte Serum - therapeutic use; Autografts; beta -Interferon; Clinical trials; Clostridium difficile; Corticoids; Cyclophosphamide; Cyclophosphamide - therapeutic use; Diarrhea; Disability Evaluation; Disease-Free Survival; Female; Follow-Up Studies; Hematopoietic Stem Cell Transplantation - methods; Hospitals; Humans; Immunosuppression; Immunosuppressive Agents - therapeutic use; Immunotherapy; Inventories; Leukocytes; Magnetic resonance imaging; Magnetic Resonance Imaging - methods; Male; Middle Aged; Monoclonal antibodies; Multiple sclerosis; Multiple Sclerosis, Relapsing-Remitting - pathology; Multiple Sclerosis, Relapsing-Remitting - therapy; Neurological complications; Neurological diseases; Neurology; Peripheral blood; Platelets; Quality of life; Rabbits; Remission; stem cell transplantation; Thrombocytopenic purpura; Transplantation, Autologous; Treatment Outcome; Young Adult
• ISSN: 1474-4422; 1474-4465
• DOI: 10.1016/S1474-4422(09)70017-1

Summary Background Autologous non-myeloablative haemopoietic stem cell transplantation is a method to deliver intense immune suppression. We evaluated the safety and clinical outcome of autologous non-myeloablative haemopoietic stem cell transplantation in patients with relapsing-remitting multiple sclerosis (MS) who had not responded to treatment with interferon beta. Methods Eligible patients had relapsing-remitting MS, attended Northwestern Memorial Hospital, and despite treatment with interferon beta had had two corticosteroid-treated relapses within the previous 12 months, or one relapse and gadolinium-enhancing lesions seen on MRI and separate from the relapse. Peripheral blood haemopoietic stem cells were mobilised with 2 g per m2 cyclophosphamide and 10 μg per kg per day filgrastim. The conditioning regimen for the haemopoietic stem cells was 200 mg per kg cyclophosphamide and either 20 mg alemtuzumab or 6 mg per kg rabbit antithymocyte globulin. Primary outcomes were progression-free survival and reversal of neurological disability at 3 years post-transplantation. We also sought to investigate the safety and tolerability of autologous non-myeloablative haemopoietic stem cell transplantation. Findings Between January, 2003, and February, 2005, 21 patients were treated. Engraftment of white blood cells and platelets was on median day 9 (range day 8–11) and patients were discharged from hospital on mean day 11 (range day 8–13). One patient had diarrhoea due to Clostridium difficile and two patients had dermatomal zoster. Two of the 17 patients receiving alemtuzumab developed late immune thrombocytopenic purpura that remitted with standard therapy. 17 of 21 patients (81%) improved by at least 1 point on the Kurtzke expanded disability status scale (EDSS), and five patients (24%) relapsed but achieved remission after further immunosuppression. After a mean of 37 months (range 24–48 months), all patients were free from progression (no deterioration in EDSS score), and 16 were free of relapses. Significant improvements were noted in neurological disability, as determined by EDSS score (p