Steroid Failure At Day 28 After Acute Graft-Versus-Host Disease Treatment and Long-Term Outcomes Following Allogeneic Transplantation: Adverse Impact On Survival and Non-Relapse Mortality But No Increasing Risk Of Relapse
Notice bibliographique
Résumé
Abstract Background Acute graft-versus-host disease (aGVHD) is one of major complications following allogeneic hematopoietic stem cell transplantation (HSCT), among which severe aGVHD affects transplantation outcomes adversely. Standard treatment option is steroids for last 4 decades. However, long-term outcomes after aGVHD according to the response to steroids therapy have not been described fully. Methods Retrospective data of 393 consecutive patients who received allogeneic HSCT at the Princess Margaret Hospital from Mar 2001 to Oct 2007 were analyzed for the response to steroid therapy and for long-terms outcomes including overall survival (OS), non-relapse mortality (NRM), incidence of relapse, development of chronic GVHD and GVHD-specific survival (GSS). Response was defined as complete response (CR; complete resolution of aGVHD signs/symptoms in all organs involved), partial response (PR; any improvement in aGVHD), stable disease (SD; no improvement or no progression of aGVHD) or progressive disease (PD; worsening of aGVHD in at least 1 organ). Steroid failure was defined the case of SD/PD at day 28. Results Out of 393 patients, 305 patients (77.6%) were diagnosed of aGVHD with grade I (n=42, 10.7%), II (n=152, 38.7%), III (n=93, 23.7%), and IV (n=18, 4.6%). Among them, 278 patients (91.1%; 70.7% out of overall population) were treated with systemic steroids. Response to steroids therapy at day 28 was as follows: CR in 137 (49.3%), PR in 85 (30.6%) and SD/PD in 49 patients (17.6%), respectively. Thus, steroid failure was noted in 49 patients (17.6%) in the present study. The risk factors of steroid failure at day 28 were aGVHD grade III-IV (OR 4.116, p<0.001) and liver stage 2-4 GVHD (OR 2.480, p=0.015). Out of 305 patients who developed aGVHD of any grade, 204 patients (66.9%) eventually developed subsequent chronic GVHD including classical type of cGVHD in 89 patients (29.2%) and overlap syndrome in 115 patients (37.7%). Among 278 patients who received steroid therapy for aGVHD, the response to steroid therapy did not show significant association with the type or severity of chronic GVHD. As expected, better survival was noted in the responder group compared to those with steroid failure at day 28. The 5-year overall survival (OS) rates were significantly better in CR (69.94.3%) or PR groups (49.46.0%) compared to SD/PD group (i.e. those with steroid failure at day 28; 24.26.5%; p<0.001). The 5-year aGVHD-specific survival (aGSS) were also different in favor of CR (83.93.4%) or PR groups (71.95.7%) compared to SD/PD group (34.88.0%; p<0.001). The non-relapse mortality (NRM) were significantly higher in SD/PD group (65.08.0%) than in PR (28.15.7%) or CR groups (16.13.4%; p<0.001), while no differences of relapse risk were observed among the groups. In multivariate analysis, the steroids failure at D+28 was an independent risk factor for OS (HR 1.916, 95% CI=1.110-3.307, p=0.020), aGSS (HR 2.213, 95% CI=1.115-4.395, p=0.023), and NRM (HR 2.462, 95% CI 1.224-4.951, p=0.011). However, steroid failure at D+28 was not a risk factor for relapse in multivariate analysis (p=0.111). Conclusion Steroids response at day 28 for aGVHD significantly affects long-term outcomes after transplant without increasing relapse risk. Early achievement of response to steroids therapy within day 28 is associated with better OS, GSS and lower NRM. Disclosures: No relevant conflicts of interest to declare.
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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 | 0,001 |
| 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 | 0,000 | 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 ».