Treatment of Steroid-Resistant Graft-Versus-Host Disease with Monoclonal Antibodies in Children.
Notice bibliographique
Résumé
Abstract Acute graft-versus-host disease (aGVHD) carries a major risk of morbidity and mortality in patients undergoing hematopoietic stem cell transplantation (HSCT). The prognosis is poor if aGVHD does not respond to corticosteroid treatment. Recently, monoclonal antibodies such as daclizumab, a humanized monoclonal IgG1, and infliximab, a chimeric monoclonal antibody that binds the precursor of tumor-necrosis factor-alfa, have shown promising results in the treatment of corticosteroid-resistant aGVHD. The reported response rate to monoclonal antibody therapy in adults with aGVHD reaches as high as 67%. Data describing the efficacy of monoclonal antibodies in children with corticosteroid-resistant aGVHD are limited. We conducted a retrospective analysis to evaluate the efficacy of daclizumab and/or infliximab in children diagnosed with steroid-resistant aGVHD in the Hospital for Sick Children, Toronto, from July 2002 to December 2005. Corticosteroid-resistant aGVHD was defined as aGVHD which did not respond or worsened after a minimum of 5 days of corticosteroid therapy. Complete response was defined as full recovery without any signs of aGVHD; partial response was defined as improvement of aGVHD symptoms in at least one organ without worsening in other organs. Sixteen children were treated for aGVHD, thirteen of them had aGVHD grade 3 or 4. The organs involved were gut (n=6), skin (n=4), liver (n=2) and multi-organ involvement (n=4). Thirteen children were given daclizumab; one was treated with infliximab and 2 children with their combination. Fourteen children received a full course of monoclonal antibodies for aGVHD. An additional child died after the first dose (from multi-organ failure) and one child developed reactive arthritis attributed to daclizumab. Seven of the 14 children (50%) who completed treatment responded: 5 had complete response and 2 had a partial response. Nine out of the 16 children died during the study period: 8 due to Transplant Related Mortality (TRM) and 1 due to relapse; three children developed fatal fungal infection and one had fatal adenovirus infection during or shortly after monoclonal antibody treatment. Median length of follow up in the remaining 7 patients was 18 months. We conclude that monoclonal antibodies were effective in the treatment of children with corticosteroid-resistant acute GVHD. The risk for infection, mainly fungal, was high.
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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 | 0,002 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,001 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 0,000 |
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 ».