Autologous Stem Cell Transplant for Myasthenia Gravis: A Single-Centre Experience
Notice bibliographique
Résumé
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.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,001 | 0,000 |
| Communication savante | 0,001 | 0,000 |
| Science ouverte | 0,000 | 0,001 |
| Intégrité de la recherche | 0,001 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 0,001 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».