Conventional Reinduction/Consolidation-Type Therapy Versus Short Course High Intensity Combination Chemotherapy As Post-Induction Treatment for Children with Relapsed Acute Lymphoblastic Leukemia. Early Results of Study ALL-REZ BFM 2002
Bibliographic record
Abstract
Abstract Abstract 871 Background: Children with relapsed ALL are at a high risk for treatment failure and require improvement of induction and consolidation therapy. Subsequent ALL-REZ BFM trials have been conducted with the aim to define risk factors and to determine adequate intensity and duration of therapy, risk-adapted SCT indication and preventive/therapeutic CNS irradiation. Short course high intensity multiagent chemotherapy elements (R-courses) have been developed as standard of care consolidation therapy of relapsed childhood ALL in countries using ALL-REZ BFM protocols. A conventionally dosed, anthracycline-containing reinduction regimen, termed “Protocol II”, which has resulted in a striking improvement of outcomes in patients with primary ALL treated with BFM protocols, may also be considered as effective consolidation therapy of relapsed childhood ALL. Aim of the study: The multi-centre prospective randomized study ALL-REZ BFM 2002 was designed to compare the efficacy and toxicity of R-courses and Protocol II-Idarubicin (Prot II-IDA) as post-induction therapy in children with relapsed ALL. Patients and methods: A total of 538 children and adolescents aged 1–18 years with first relapse of acute lymphoblastic leukaemia were enrolled in approximately 100 hospitals in Germany, Austria, Switzerland, Czech Republic and Toronto, Canada. 420 patients (78%) were randomized to receive either Prot II-IDA or R-courses as post-induction therapy after uniform induction with F1/2 courses. Further treatment was stratified according to risk groups S1-4: Patients in group S1 (late isolated extramedullary relapse) received 3 more R-courses, local irradiation and maintenance chemotherapy. Patients in group S3/4 (early and very early precursor B cell and any T cell bone marrow relapse) received allogeneic hematopoietic stem cell transplantation (HSCT) from any donor. Patients in group S2 (intermediate risk, all others) were stratified according to the level of minimal residual disease (MRD) in the bone marrow after induction therapy, measured with a PCR-based, centrally reviewed assay: MRD good responders (<10e-3) received 5 additional R-courses followed by maintenance chemotherapy. MRD poor responders (≥10e-3) went on to HSCT from a well matched allogeneic donor. Results: 210 patients were allocated to Prot II-IDA course and 210 patients were allocated to R-courses. The randomized groups were well-balanced with respect to relevant clinical parameters including the proportion of patients receiving stem cell transplantation. The estimated 5-year probabilities of event-free survival (pEFS) of the two randomized groups (Prot II-IDA: 0.60 ± 0.04 vs. R-courses: 0.53 ± 0.04, P = 0.30) and overall survival (pOS, Prot II-IDA: 0.69 ± 0.04 vs. R-courses: 0.63 ± 0.04, P = 0.46) were not significantly different. However, the cumulative incidence of subsequent relapse was significantly lower in the Prot II-IDA arm (0.21 ± 0.01) compared to patients treated with R-courses (0.30 ± 0.01, p = 0.03). Treatment-related mortality was mainly associated with HSCT and not different in both arms (0.05 vs. 0.03). Whereas hematological toxicity was higher with Prot II-IDA, more patients suffered from mucositis with R-courses. Conclusion: More than 50% of children with relapsed ALL could be cured with the ALL-REZ BFM 2002 strategy. Post-induction therapy with Protocol II-IDA was associated with fewer subsequent relapses compared to R-courses. Toxicity was acceptable and EFS/OS probabilities were not different in both study arms. Protocol II-IDA will be taken forward as standard post-induction therapy in future ALL-REZ BFM trials. Disclosures: No relevant conflicts of interest to declare.
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) | 0.001 | 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".