Autologous Stem Cell Transplant for Myasthenia Gravis: A Single-Centre Experience
Bibliographic record
Abstract
Abstract Myasthenia Gravis is an antibody-mediated disease that affects the neuromuscular junction. Despite advances in immune-targeted therapies, a subset of patients demonstrate refractory disease with severe or life-threatening symptoms. Disease control has been achieved using autologous hematopoietic stem cell transplant (HSCT) in a variety of autoimmune conditions including multiple sclerosis, chronic inflammatory demyelinating polyneuropathy, stiff person syndrome, and others. Here we report our center’s experience using autologous HSCT in seven patients with myasthenia. Seven myasthenia patients underwent HSCT between 2001 and 2011. Six patients were female. Median age (range) was 37 at diagnosis (17-52) and 43 at HSCT (24-55). Before HSCT, myasthenia severity, standardized by the Myasthenia Foundation of America (MGFA) clinical classification, was graded as moderate in 2 patients, severe in 3 patients, and life-threatening in 2 patients. Treatment regimens included pyridostigmine in all patients, and immune-targeted therapies including: steroid therapy in all patients, an additional immunomodulating drug in 6 patients, and plasma exchange or intravenous immunoglobulin in all patients. All patients had at least one myasthenia-related emergency department visit or hospitalization prior to HSCT, 3 requiring ICU stays and 2 requiring intubation. All patients underwent HSCT mobilization with cyclophosphamide and filgrastim. Stem cells were harvested from peripheral blood and selected for CD34+ cells in all cases. Conditioning regimens used busulfan, cyclophosphamide, and antithymocyte globulin (Bu-Cy-ATG) in 4 patients, Cy-ATG and total body irradiation in 2 patients, and etoposide, melphalan and dexamethasone in 1 patient who was undergoing HSCT for relapsed follicular lymphoma (FL). Median post-HSCT follow-up was 40 months (range 29-149). At last follow-up MGFA postintervention status was classified as complete stable remission (CSR) in all patients, indicating patients bad been experiencing no myasthenia symptoms and were on no myasthenia therapy for at least one year. Six patients had no further hospitalizations or emergency department visits post HSCT. One patient required hospitalizations in the 6 months post HSCT but at time of writing had been not hospitalized for myasthenia for more than 10 years. One patient died 29 months post HSCT from relapsed FL. At time of death this patient’s myasthenia was in CSR. There were no HSCT regimen-related deaths. No patients required ICU care during HSCT admission. Absolute neutrophil count exceeded 0.5 x 109/L on median post HSCT day 11 (range 13 - 28). Median hospital stay, including administration of conditioning regimen was 34 days (range 20-43). In the first post-HSCT year the cohort experienced 6 viral reactivations in 3 patients: 3 cases CMV viremia, 1 case BK virus-induced hemorrhagic cystitis, 1 case VZV dermatitis, 1 case oral HSV. Two late post-HSCT complications were observed: one case of acquired amegakaryocytic thrombocytopenia (post-HSCT day 701), and one case of relapsed FL (post-HSCT day 846) resulting in patient death. HSCT resulted in longstanding symptom- and treatment-free remission in seven patients with refractory myasthenia gravis. The procedure was tolerable however the intense immune depletion transiently increased risk of viral reactivation. This experience demonstrates that in selected myasthenia gravis cases, HSCT is a viable option for long-term disease control. The novel application of HSCT for this and other autoimmune conditions is an area that warrants further exploration and long-term follow-up. Disclosures No relevant conflicts of interest to declare.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".