Secondary Chromosomal Abnormalities Appear to Be Less Prognostic for Children with Philadelphia Chromosome Positive (Ph+) Acute Lymphoblastic Leukemia (ALL) Treated with Intensified Imatinib and Chemotherapy: Results of the Children's Oncology Group (COG) Study AALL0031.
Notice bibliographique
Résumé
Abstract Abstract 2606 Poster Board II-582 Background: Secondary chromosomal aberrations at diagnosis occur frequently in both pediatric and adult patients with Ph+ ALL. Several studies have shown that the presence of additional cytogenetic abnormalities is a major negative prognostic factor among children and adults with Ph+ ALL. A Japanese study in adults with Ph+ ALL indicated that the adverse prognostic significance of secondary rearrangements was seen even in patients treated with imatinib-combined chemotherapy including consolidation with blood and marrow transplantation (BMT) (Haematologica 92:287, 2008). Two-year EFS in that study was 48.5±5.7%, and the 50 patients with secondary chromosomal abnormalities had a 35% - 40% lower EFS than those with t(9;22) only (p=0.003). COG AALL0031 treated children with imatinib in combination with intensive chemotherapy. This study had an overall 3 year EFS of 80±11% for those receiving chemotherapy only, an outcome similar to those receiving allogeneic BMT. We evaluated the impact of secondary chromosomal abnormalities in children and adolescents receiving this regimen. Methods: Children and adolescents (age 1–21 years) with Ph+ ALL enrolled on AALL0031 after completing 3- or 4-drug induction therapy. Imatinib was given at 340mg/m2/day for an increasing number of days in combination with an intense chemotherapy backbone. Cohort 4 received imatinib for 126 (N=12) and cohort 5 for 280 continuous days (N=50) prior to maintenance therapy. The first two cycles of the intensive chemotherapy included ifosfamide and etoposide (cycle 1) and high dose (HD) methotrexate and HD cytarabine (cycle 2). Patients were non-randomly assigned to an HLA-identical related donor BMT, if a donor was available, or to an intensive chemotherapy regimen that continued for approximately 2.2 years. Unrelated donor BMT was not allowed; these patients were taken off protocol but included in survival evaluation by an intent-to-treat evaluation. Results: Satisfactory cytogenetic results were available for 71 (76%) of 93 enrolled children. Secondary aberrations were present in 46 (65%) patients. The most frequent secondary aberrations were +der(22) (N=21), =50 chromosomes (N=14), −7/del(7p) (N=11), abnormal (9p) (N=7), and +8 (N=5). The overall 3 year CCR was 79±6% for patients in cohorts 4/5, including those with non evaluable cytogenetics (N=55). When outcome analyses were limited to Ph+ ALL patients in cohorts 4/5 (N=43), three-year CCR for patients with Ph+ alone (N=14) was 86±10% versus 71±9% for those with Ph+ and secondary abnormalities (N=29) (p=0.19). Conclusions: In this study, the lower 3 year CCR seen in patients with Ph+ ALL with secondary chromosomal abnormalities was not significantly different than for children with Ph+ alone possibly reflecting small patient numbers. The lower 3 year CCR for Ph+ ALL with secondary chromosomal abnormalities in those treated on AALL0031 (∼15% lower) appeared to be less than that seen in the previous adult trial (∼35%). This may be the result of the addition of imatinib to intensified chemotherapy reducing the poor prognostic significance of additional chromosome abnormalities seen in previous studies. Larger patient numbers and longer follow-up will be necessary to answer this question. Disclosures: Schultz: DOR Biopharma: Membership on an entity's Board of Directors or advisory committees; Genzyme Canada: Membership on an entity's Board of Directors or advisory committees.
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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 | 0,002 |
| 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 | 0,001 |
| 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 ».