PS981 LONG TERM AML SURVIVORS HAVE INCREASED MORTALITY AND HIGH PREVALENCE OF CLONAL HEMATOPOIESIS
Notice bibliographique
Résumé
Background: Acute myeloid leukemia (AML) is defined by the accumulation of immature blasts in the bone marrow (BM) resulting, if left untreated, in acute BM failure. While AML presents in an acute form, it is clear today that most AML cases are preceded by a long phase of age related clonal hematopoiesis (ARCH) with almost no symptoms. The clinical and molecular trajectories of AML both before and after diagnosis are highly predictable. Recent studies identified the high risk individuals destined to evolve from ARCH to AML based on blood counts parameters (mainly red cell distribution width (RDW)) and molecular attributes such as clone size and the number of ARCH defining events. Most AML patients will achieve complete remission after induction chemotherapy, however most will relapse within a median time of 11 months despite post remission consolidation or bone marrow transplantation (BMT). A small fraction of AML patients will maintain at long term remission (LTR). Aims: The course of AML from ARCH to relapse is well characterized both clinically and molecularly, however, this information is missing for long term AML survivors, specifically for AML patients who did not receive BMT. The fact that AML has a long chronic history before its acute presentation might suggest that a recovery from the acute phase will not necessary result in resetting the hematopoietic system but rather to turn it back to its chronic phase before AML presentation. Methods: To answer the question whether preleukemic events are still present at LTR and what important clinical implications it might have, we studied morbidity, mortality and molecular structure among two unique LTR cohorts. One cohort is the electronic health records (HER) of 4.2 million individuals covering over 15 years of follow up and include 61 LTR survivors who did not undergo BMT (LTSnoBMT). The second cohort which contains molecular data, included analysis of genetic variation in 30 LTR cases at diagnosis and LTR, and was compared to a group of lymphoid malignancies patients at remission. Results: We found that the mortality among LTSnoBMT 10 years after diagnosis was 20%>50% higher in comparison to controls. In addition, several lab results were different between the LTSnoBMT and controls including higher red cell distribution width (RDW) among older (>55) LTSnoBMT. Recent studies found a correlation between high RDW and mortality among individuals carrying age related clonal hematopoiesis (ARCH) mutations. We also found that ARCH defining events were significantly more prevalent among LTSnoBMT in comparison to controls (63% vs 37% p = 0.039). Furthermore of the ARCH defining events among the LTSnoBMT 62% were recurrent AML variants as oppose to 21% among the controls (p = 0.002). Of the recurrent mutations IDH1/2 were the most common mutations and 2 out of 7 IDH1/2 cases experienced a late relapse (Figure 1). Summary/Conclusion: Altogether, even after the sustainable eradication of the malignant clone, the hematopoietic system/microenvironment does not normalize (abnormal blood counts, high prevalence of ARCH and higher mortality). image These results suggest that AML at LTR is a unique situation and that this group of patients are not fully recovered and should be further studied and treated.
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 distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 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) | 0,004 | 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 tête enseignante, 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 ».