title: Myasthenia Gravis Treated With Autologous Hematopoietic Stem Cell Transplantation.
abstract: Some patients with myasthenia gravis (MG) do not respond to conventional treatment and have severe or life-threatening symptoms. Alternate and emerging therapies have not yet proved consistently or durably effective. Autologous hematopoietic stem cell transplant (HSCT) has been effective in treating other severe autoimmune neurologic conditions and may have similar application in MG.
  
  
  
  To report 7 cases of severe MG treated with autologous HSCT in which consistent, durable, symptom-free, and treatment-free remission was achieved.
  
  
  
  This retrospective cohort study reports outcomes at The Ottawa Hospital, a large, Canadian, tertiary care referral center with expertise in neurology and HSCT, from January 1, 2001, through December 31, 2014, with a median follow-up of 40 months (range, 29-149 months). Data collection and analysis were performed from February 1 through August 31, 2015. All patients with MG treated with autologous HSCT at The Ottawa Hospital were included. All had persistent severe or life-threatening MG-related symptoms despite continued use of intensive immunosuppressive therapies.
  
  
  
  Autologous hematopoietic stem cell grafts were mobilized with cyclophosphamide and granulocyte colony-stimulating factor, collected by peripheral blood leukapheresis, and purified away from contaminating lymphocytes using CD34 immunomagnetic selection. Patients were treated with intensive conditioning chemotherapy regimens to destroy the autoreactive immune system followed by graft reinfusion for blood and immune reconstitution.
  
  
  
  The primary outcome was MG disease activity after autologous HSCT measured by frequency of emergency department visits and hospitalizations and Myasthenia Gravis Foundation of America (MGFA) clinical classification, MGFA therapy status, and MGFA postintervention status. Safety outcomes included all severe autologous HSCT-related complications.
  
  
  
  Seven patients underwent autologous HSCT, 6 for MG and 1 for follicular lymphoma with coincident active MG. Mean (SD) ages at MG diagnosis and at autologous HSCT were 37 (11) and 44 (10) years, respectively. Five patients (71%) had concurrent autoimmune or lymphoproliferative illnesses related to immune dysregulation. All patients had distinct clinical and electromyographic evidence of MG (MGFA clinical classification IIIb-V). All patients achieved durable MGFA complete stable remission with no residual MG symptoms and freedom from any ongoing MG therapy (MGFA postintervention status of complete stable remission). Three patients (43%) experienced transient viral reactivations, and 1 (14%) developed a secondary autoimmune disease after autologous HSCT, all of which resolved or stabilized with treatment. There were no treatment- or MG-related deaths.
  
  
  
  Autologous HSCT results in long-term symptom- and treatment-free remission in patients with severe MG. The application of autologous HSCT for this and other autoimmune neurologic conditions warrants prospective study.
authors.affiliation: Division of Hematology, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Adam
authors.initials: A
authors.lastname: Bryant
authors.affiliation: Division of Hematology, University of Ottawa, Ottawa, Ontario, Canada2The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada3The Bone Marrow Transplant Programme, University of Ottawa, The Ottawa Hospital, Ottawa, Ontario, Canada.
authors.forename: Harold
authors.initials: H
authors.lastname: Atkins
authors.affiliation: Division of Neurology, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: C Elizabeth
authors.initials: CE
authors.lastname: Pringle
authors.affiliation: Division of Hematology, University of Ottawa, Ottawa, Ontario, Canada2The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada3The Bone Marrow Transplant Programme, University of Ottawa, The Ottawa Hospital, Ottawa, Ontario, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Allan
authors.affiliation: The Bone Marrow Transplant Programme, University of Ottawa, The Ottawa Hospital, Ottawa, Ontario, Canada.
authors.forename: Grizel
authors.initials: G
authors.lastname: Anstee
authors.affiliation: Division of Hematology, University of Ottawa, Ottawa, Ontario, Canada3The Bone Marrow Transplant Programme, University of Ottawa, The Ottawa Hospital, Ottawa, Ontario, Canada.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Bence-Bruckler
authors.affiliation: The Bone Marrow Transplant Programme, University of Ottawa, The Ottawa Hospital, Ottawa, Ontario, Canada.
authors.forename: Linda
authors.initials: L
authors.lastname: Hamelin
authors.affiliation: The Bone Marrow Transplant Programme, University of Ottawa, The Ottawa Hospital, Ottawa, Ontario, Canada5Department of Pharmacy, The Ottawa Hospital, Ottawa, Ontario, Canada.
authors.forename: Michael
authors.initials: M
authors.lastname: Hodgins
authors.affiliation: Department of Pharmacy, The Ottawa Hospital, Ottawa, Ontario, Canada.
authors.forename: Harry
authors.initials: H
authors.lastname: Hopkins
authors.affiliation: The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada3The Bone Marrow Transplant Programme, University of Ottawa, The Ottawa Hospital, Ottawa, Ontario, Canada.
authors.forename: Lothar
authors.initials: L
authors.lastname: Huebsch
authors.affiliation: The Bone Marrow Transplant Programme, University of Ottawa, The Ottawa Hospital, Ottawa, Ontario, Canada.
authors.forename: Sheryl
authors.initials: S
authors.lastname: McDiarmid
authors.affiliation: Division of Hematology, University of Ottawa, Ottawa, Ontario, Canada2The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada3The Bone Marrow Transplant Programme, University of Ottawa, The Ottawa Hospital, Ottawa, Ontario, Canada.
authors.forename: Mitchell
authors.initials: M
authors.lastname: Sabloff
authors.affiliation: Division of Hematology, University of Ottawa, Ottawa, Ontario, Canada3The Bone Marrow Transplant Programme, University of Ottawa, The Ottawa Hospital, Ottawa, Ontario, Canada.
authors.forename: Dawn
authors.initials: D
authors.lastname: Sheppard
authors.affiliation: Division of Hematology, University of Ottawa, Ottawa, Ontario, Canada2The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada3The Bone Marrow Transplant Programme, University of Ottawa, The Ottawa Hospital, Ottawa, Ontario, Canada.
authors.forename: Jason
authors.initials: J
authors.lastname: Tay
authors.affiliation: Division of Hematology, University of Ottawa, Ottawa, Ontario, Canada2The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada3The Bone Marrow Transplant Programme, University of Ottawa, The Ottawa Hospital, Ottawa, Ontario, Canada.
authors.forename: Christopher
authors.initials: C
authors.lastname: Bredeson
mesh_terms: D000328:Adult; D000906:Antibodies / Q000627:therapeutic use; D018952:Antigens, CD34 / Q000276:immunology / Q000378:metabolism; D015331:Cohort Studies; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009157:Myasthenia Gravis / Q000188:drug therapy / Q000601:surgery*; D013997:Time Factors; D014182:Transplantation, Autologous / Q000379:methods; D016896:Treatment Outcome
chemical_list: D000906:Antibodies; D018952:Antigens, CD34; D007155:Immunologic Factors