Results Of The DFCI ALL Consortium Protocol 05-001 For Children and Adolescents With Newly Diagnosed ALL
Bibliographic record
Abstract
Abstract Current treatment regimens for childhood ALL have resulted in long-term event-free survival (EFS) of approximately 80%. On DFCI ALL Consortium Protocol 05-001, patients (pts) with newly diagnosed ALL aged 1-18 years (yrs) who achieved complete remission (CR) were eligible to participate in a randomized comparison of native E.coli asparaginase (ASP) given intramuscularly (IM) and PEG ASP, the polyethylene glycol conjugate of E.coli ASP, given intravenously (IV). The objective was to compare the serum ASP activity (SAA), toxicity, and EFS of the two ASP preparations. An intensified consolidation regimen for VHR pts, including B-ALL pts with high end-induction minimal residual disease (MRD), was also evaluated. Methods All pts received 1 dose of PEG ASP (2500 IU/m2) during the 4-week (wk) multiagent induction phase. After CR was achieved, final risk group was assigned based on age, presenting WBC, CNS status, cytogenetics and end-induction MRD (assessed by PCR). All T-ALL pts were considered HR. Pts were considered VHR if they met one of the following criteria: i) B-ALL with high end-induction MRD; or ii) adverse cytogenetics (MLL gene rearrangement or hypodiploidy). BCR-ABL positive pts began daily imatinib at Day 18 and were allocated to allogeneic transplant in 1st CR. Beginning at wk 7, pts began the consolidation phase including 30 wks of ASP, either IM E.coli ASP 25000 IU/m2 weekly or IV PEG 2500 IU/m2 every 2 wks. In addition, SR pts received every 3-wk cycles with vincristine, dexamethasone, 6MP and low-dose methotrexate (mtx) during consolidation; HR pts received doxorubicin (cumulative dose 300 mg/m2) with dexrazoxane instead of mtx during this phase. VHR pts received 2 additional cycles beginning at week 7 (cyclophosphamide/low-dose araC/6-MP and then high-dose araC/etoposide/dexamethasone), followed by the HR consolidation phase. Continuation phase was identical for all pts. Total duration of therapy was 25 months. Serum samples were obtained every 6 wks just prior to an ASP dose to measure SAA. EFS rates were calculated from date of registration, except for EFS by randomized arm, risk group, and end-induction MRD, which were calculated from time of randomization. Results Between 2005-2010, 551 evaluable pts enrolled, of whom 526 (95%) achieved CR. 463 pts participated in the ASP randomization. Median nadir SAA was significantly higher with IV PEG than with IM E.coli ASP,(Table 1) with more IV PEG-randomized pts achieving nadir SAA ≥ 0.1 IU/mL (p<0.01 at each time point). There was no significant difference in ASP-related allergy (p=0.36) and pancreatitis (p=0.54) between the two arms, and a trend toward more thrombotic events with E.coli ASP (p=0.07). With 4.5 yrs median follow-up, the 4-yr EFS for all 551 pts was 86% [95% CI 82-88%]. Outcome by pt characteristics are displayed in Table 2. The 4-yr EFS for B-ALL pts with high end-induction MRD was 77% [95% CI 60-88%]. There was no difference in EFS between the randomized arms (p=0.31). Conclusion Overall EFS on Protocol 05001 compares favorably with previously published outcomes for pediatric ALL. Intensified consolidation improved outcome for B-ALL pts with high end-induction MRD. Relatively favorable outcomes were also observed in other high-risk pt subsets, including older children/adolescents and pts with T-ALL. We have demonstrated that IV PEG is as effective as and no more toxic than weekly IM E.coli ASP in children and adolescents with ALL. Disclosures: Silverman: Sigma Tau Pharmaceuticals: Consultancy. Andrew:Sigma Tau Pharmaceuticals: Consultancy. Neuberg:Synta Pharmaceuticals: Trust owns stock; I am a Trustee Other. Sallan:Sigma Tau Pharmaceuticals: Consultancy.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".