Adam Bryant, MD; Harold Atkins, MD, FRCPC; C. Elizabeth
Pringle, MD; David Allan, MD, MSc; Grizel Anstee, MD; Isabelle Bence-Bruckler,
MD, FRCPC; Linda Hamelin, MScN; Michael Hodgins, MD; Harry Hopkins, RPh, FCSH;
Lothar Huebsch, MD, FRCPC, Sheryl McDiarmid, MBA; Mitchell Sabloff, MD, FRCPC;
Dawn Sheppard, MD, MSc, FRCPC; Jason Tay, MD, MSc, FRCPC; Christopher Bredeson,
MD, MSc, FRCPC. Myasthenia Gravis Treated With Autologous Hematopoietic Stem
Cell Transplantation. JAMA Neurology.
Online.
Abstract
Importance 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.
Objective To report 7
cases of severe MG treated with autologous HSCT in which consistent, durable,
symptom-free, and treatment-free remission was achieved.
Design, Setting, and Participants 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.
Interventions
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.
Main Outcomes and Measures
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.
Results 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.
Conclusions and Relevance
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.
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