Factors influencing outcomes in therapy-related myeloid neoplasms following allogeneic hematopoietic stem cell transplantation
Notice bibliographique
Résumé
Abstract Introduction: Therapy-related myeloid neoplasms (t-MN), including therapy-related myelodysplastic syndrome (t-MDS) and acute myeloid leukemia (t-AML), arise after exposure to cytotoxic or immunosuppressive treatments. Although the 2022 International Consensus Classification (ICC) no longer recognizes t-MN as distinct, the term persists due to historically poor prognosis. Many cases, however, have favorable or intermediate-risk genetics. This study examines clinical and molecular predictors of outcomes after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in t-MN. Methods: We retrospectively analyzed 141 t-MN patients who underwent allo-HSCT from Jan 2010 to May 2024. Collected variables included demographics, prior therapies, disease features, transplant parameters, and outcomes. The primary endpoint was 2-year overall survival (OS); secondary endpoints were 2-year non-relapse mortality (NRM) and cumulative incidence of relapse (CIR). Kaplan-Meier and competing risk analyses were performed. Results: Among 141 patients (median age 60; 47% male), 62.4% had t-AML, 33.3% t-MDS, and 4.3% other diagnoses. Median time from primary disease to t-MN was 6 years. In t-AML, prior cancers included solid tumors (48.9%) and hematologic neoplasms (35.2%), with 17% having had autologous HSCT. In t-MDS, 74.5% had prior hematologic malignancy and 51.1% had prior autologous HSCT. Overall, 85% had a history of cytotoxic therapy. Pre-HSCT therapies included induction chemotherapy (61%), hypomethylating agents (HMA) alone (22%), HMA plus venetoclax (7.1%), or none (7.8%). Common cytogenetics were chromosome 7 abnormalities (27%), complex karyotype (20.6%), monosomal karyotype (24.1%), and TP53 mutations (7.1%). ELN 2022 risk classification: 12.1% favorable, 39.6% intermediate, 37.4% adverse. With 2-year median follow-up, OS was 52.8%, NRM 29.2%, and CIR 21.1%. Grade II–IV acute GVHD occurred in 26.2%; chronic GVHD in 30.2% (with moderate or severe cases in 20.2%). OS was higher in t-AML vs. t-MDS (57.3% vs. 40.6%, p=0.045). Outcomes did not significantly differ by primary disease type: OS was 50.2% for solid tumors, 53.6% for hematologic neoplasms, 58.8% for benign diseases (p=0.42); NRM: 28.3%, 29.9%, 29.4% respectively (p=0.58); CIR: 25.9%, 19.6%, 11.8% (p=0.31). Among prior hematologic malignancies, prior autologous HSCT did not impact OS, NRM, or CIR. In t-AML, the 2022 European LeukemiaNet (ELN) risk stratification showed 2-year OS: 63.6% (favorable), 62.8% (intermediate), 54.8% (adverse) (p=0.42). NRM did not significantly differ (36.4%, 28.0%, 9.4%; p=0.15), but CIR was higher in adverse (42.1%) vs. intermediate (11.4%) and favorable (0%) (p=0.002). Using the Disease Risk Index (DRI) classification (Armand et al., Blood 2014), 2-year OS was 66.7% (low-risk), 59.5% (intermediate-risk), and 36.5% (high-risk) (p=0.007). NRM: 33.3% (low-risk), 29.6% (intermediate-risk), 27.2% (high-risk) (p=0.99); CIR: 6.0% (low-risk), 12.7% (intermediate-risk), 42.8% (high-risk) (p<0.001). Adverse cytogenetics were associated with inferior outcomes: complex karyotype (OS 35.3% vs. 58.4%, p=0.02; CIR 48.2% vs. 16.1%, p<0.001), chromosome 7 abnormalities (OS 31.1% vs. 61.1%, p<0.001; CIR 43.1% vs. 15.2%, p<0.001), del(5q) (OS 29.2% vs. 55.9%, p=0.005; CIR 56.2% vs. 18.2%, p<0.001). At the time of analysis, no patient with both TP53 mutation and complex karyotype survived beyond 2 years. Conditioning intensity and chronic GVHD severity did not affect OS. Multivariable analysis identified Karnofsky performance status (KPS) <90, chromosome 7 abnormalities, and del(5q) as adverse OS predictors. Chromosome 7 abnormalities, del(5q), and bone marrow graft source were associated with higher relapse. Conclusion: Allo-HSCT offers curative potential for t-MN. Outcomes were better in t-AML vs. t-MDS. ELN 2022 effectively predicted relapse, but DRI better predicted both OS and CIR. Adverse cytogenetics (complex karyotype, del(5q), chromosome 7 abnormalities, TP53 mutations) predicted poor survival. These findings underscore the importance of molecular risk stratification and highlight the need for innovative therapies for high-risk groups.
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 | 0,002 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 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) | 0,002 | 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 ».