Outcomes of Adult Philadelphia Positive Acute Lymphoblastic Leukemia Patients Treated with Pediatric Multi-Agent Chemotherapy and Imatinib and the Impact of Residual Disease Monitoring on Survival
Notice bibliographique
Résumé
Abstract The prognosis of Philadelphia positive acute lymphoblastic leukemia (Ph+ ALL) has improved markedly after the introduction of BCR ABL1 targeted tyrosine kinase inhibitors (TKI). With the addition of upfront TKI, ~90 % of patient will achieve complete remission (CR). Allogenic stem cell transplant (alloSCT) remains the cornerstone of post remission therapy based on large trials that predate the introduction of TKIs. This approach has since been challenged in more recent studies in which similar outcomes were observed with lifetime TKI therapy. Several reports have suggested a correlation between achieving a molecular negativity with chemotherapy + TKI and long term outcome, in patients who did not receive alloSCT, suggesting that a monitoring strategy might spare some patients with excellent response to chemotherapy and TKI the toxicity of (alloSCT), and with comparable outcome. We previously reported good overall survival and event free survival in patients treated with a TKI-modified version of the Dana Farber Cancer Institute (DFCI) pediatric ALL protocol. In this retrospective analysis we compared the long term outcome of Ph+ ALL patients who were transplanted and those who were not, mainly due to the unavailability of a donor. In addition, we reviewed the effect of residual disease monitoring (RDM) at post induction, 3, 6, 9 and 12 months, and correlated the achievement of complete and major molecular responses with survival. In the present study, 167 patients diagnosed with Ph+ ALL in our center were evaluated from year 2001-2015. One hundred and thirty three (133) received DFCI chemotherapy + imatinib. One hundred and nineteen (119; 89%) patients achieved CR following the induction phase. Fifty nine (59; 44.3 %) subsequently received an allogenic stem cell transplant from a sibling or matched unrelated donor, leaving 74 patients who were not transplanted and were evaluated for RDM. While there was no significant difference between the overall survival (OS) for the transplanted and not transplanted cohorts (median survival 3.3 years vs 5.3 years, and 5 year- OS 40% vs 50 %, respectively; p value = 0.40), there was an improved relapse free survival (RFS) in the transplanted group (5- year RFS, 55% vs 75%, respectively; p value= 0.033). Achieving CMR with un-detectable transcripts post-induction, and at 3 and 6 months, showed superior OS compared to those not achieving CMR (p values of 0.029, 0.0086 and 0.028, respectively), whereas superior RFS was associated with molecular negativity at 3, 6 and 9 months ( p values of 0.0076,0.0023 and 0.03, respectively). Molecular negativity at 12 months had no impact on survival. In conclusion, our data confirm that while the RFS of patients with Ph+ ALL who did not undergo alloSCT as post remission therapy was inferior to that of those who did, OS was similar in the two groups. Monitoring of residual disease at early time points during therapy, and especially at 3 and 6 months, appears to identify patients with a lower chance of relapse who can likely be spared the toxicity of alloSCT, and receive chemotherapy + TKI, followed by ongoing TKI maintenance. Further RDM studies are needed to better stratify such patients and to facilitate alloSCT decision making. Figure Figure. Disclosures Gupta: Incyte Corporation: Consultancy, Research Funding; Novartis: Consultancy, Honoraria, Research Funding. Schimmer:Novartis: Honoraria. Schuh:Amgen: Membership on an entity's Board of Directors or advisory committees.
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 | 0,001 | 0,001 |
| 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) | 0,001 | 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 ».