Philadelphia-Negative Clonal Hematopoiesis Following Imatinib Therapy in Patients with Chronic Myeloid Leukemia (CML).
Notice bibliographique
Résumé
Abstract There is an increasing number of reports of Philadelphia-negative (Ph-) clonal hematopoiesis developing in patients (pts) with CML treated with imatinib. The significance of these abnormalities remains unclear. To examine the incidence, natural history and risk factors for the development of Ph- clones, we undertook a retrospective review of 142 consecutive pts with CML treated with imatinib and followed at VGH or BCCA between June 1999 and July 2004. Four pts were excluded due to incomplete records. Out of 138 pts, there were 76 (55%) males. The median age at diagnosis was 48.6 yrs (range 19.3–82.8). At the time of initiation of imatinib, 93 (67%) pts were in stable phase, 33 (24%) in accelerated phase and 12 (9%) in blast phase. 126 pts had received prior therapy with hydroxyurea (81%), interferon (53%), hematopoietic stem cell transplantation (17%), cytarabine (11%), or other therapy (17%). The median number of prior therapies was 2 (range 0–4). The median time from diagnosis to treatment with imatinib was 12.7 mos (range 0–240.1) and the median duration of imatinib therapy was 15.2 mos (range 0.6–45.1). Best responses to imatinib were complete hematologic response (96%), major cytogenetic response (53%) and complete cytogenetic response (43%). The event-free survival (EFS) at 3 yrs from the start of imatinib was 59% (95%CI 47–70%). Of the 138 pts, 7 (5%) pts developed Ph- clonal abnormalities: −7 and +8 (2 pts), +8 (2 pts), −7 (1 pt), −X and −22 (1 pt) and t(12;16) (1 pt). One pt had −7 and 1 pt had +8 in both Ph- and Ph+ cells. For the pts who developed Ph- clonal abnormalities, the median time from diagnosis to the start of imatinib was 28.4 mos (range 0.7–143.9). Six of these 7 pts had received prior therapy. The median time from the start of imatinib therapy to the development of the Ph- clone was 11.9 mos (range 2.7–23.5). All but two of the Ph- clones were transient and none was associated with myelodysplasia. Two of the 7 pts had progressed on imatinib. There was no difference in EFS or overall survival between pts with or without Ph- clones. In univariate analysis comparing characteristics of pts with and without Ph- clones, no predictive factors could be identified. In conclusion, the development of Ph- clonal hematopoiesis in pts with CML treated with imatinib occurred in ~5% of this series and did not appear to confer a worse prognosis. The majority of the Ph- clones included −7 and/or +8 and were transient without associated myelodysplasia. Finally, the observation of −7 (to our knowledge the first such case reported) or +8 in both Ph- and Ph+ cells in the same patient could be explained by the existence of a Ph- monoclonal state prior to the BCR/ABL mutation.
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 | 0,001 | 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 ».