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.
Bibliographic record
Abstract
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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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".