A Simple Tool for the Prediction of Azacytidine Treatment Failure in Patients with Myelodysplastic Syndrome
Notice bibliographique
Résumé
Introduction:The development of a tool to predict the sensitivity of MDS patients to azacytidine has great clinical applicability. Furthermore, a tool that is able to dynamically predict response to azacytidine while on therapy would be of utility to the clinician who must determine when the efficacy of the drug has been lost. Goal: The purpose of this work was to evaluate clinical and laboratory parameters to develop markers of ineffective hematopoiesis that correlate with the development of resistance to azacytidine in MDS patients. Methods: We conducted a retrospective cohort study of all patients with MDS with Int-2/hi risk IPSS score treated with 5-azacytidine at the London Health Science Centre between January 2008 and December 2014. The study was approved by the institutional Research Ethics Board. Relevant data, including bone marrow aspirate and biopsy, cytogenetics, peripheral blood counts, transfusion frequency, and azacytidine dosing and administration were extracted from the electronic patient record. Response to azacytidine, as assessed by IWG 2006 criteria, was recorded and time to treatment failure was calculated. The parameter representative of ineffective erythropoiesis was derived using an ROC curve generated by comparing the RDW during time periods of low red blood cell transfusion burden to time periods of high transfusion burden. Parameters representative of ineffective hematopoiesis in each of the megakaryocytic and granulocytic lineages were derived using ROC curves generated by comparing changes in each of the respective counts during time periods with effective erythropoiesis and known azacytidine treatment response (based on bone marrow blast counts and cytogenetic profile), and time periods with effective erythropoiesis and proven treatment failure. The parameter for ineffective erythropoiesis was defined as hemoglobin Results: The characteristics of all MDS patients included in the cohort is summarized in Table 1. There was a total of 97 patients in the cohort, with 74 patients receiving greater than 3 treatment cycles and having sufficient response data for the derivation of hematopoietic parameters. The presence of ineffective erythropoiesis after the 3rd cycle of azacytidine had a significant correlation with the time to treatment failure (Figure 1). The median time to treatment failure of MDS patients was 144 days for patients with ineffective erythropoiesis after 3 cycles of azacytidine, while it was 418 days for patients with effective erythropoiesis. The parameters for ineffective megakaryopoiesis and ineffective granulopoiesis after 3 cycles of azacytidine had no correlation with time to treatment failure. There were 25 patients who attained response to azacytidine beyond 6 cycles and who had proven treatment failure based on either increasing blast count or cytogenetic evolution along with sufficient peripheral blood count data corresponding to the time of treatment failure. Among these patients, the development of ineffective granulopoiesis followed by the development of ineffective megakaryopoiesis had a positive predictive value of 87% for disease progression. Conclusion: The presence of ineffective erythropoiesis after 3 cycles of azacytidine was the strongest predictor of azacytidine treatment failure in Int-2/Hi IPSS MDS patients. The earliest peripheral blood markers of disease progression after initial response reflect the development of ineffective granulopoiesis followed by ineffective megakaryopoiesis, with effective erythropoiesis preserved. Download : Download high-res image (207KB) Download : Download full-size image Disclosures Lazo-Langner: Daiichi Sankyo: Research Funding; Alexion: Research Funding; Bayer: Honoraria; Pfizer: Honoraria.
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 | 0,003 | 0,012 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,001 |
| Bibliométrie | 0,007 | 0,002 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,001 | 0,001 |
| Intégrité de la recherche | 0,001 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,003 | 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 ».