Use of tyrosine kinase inhibitors for paediatric Philadelphia chromosome-positive acute lymphoblastic leukaemia: a systematic review and meta-analysis
Bibliographic record
Abstract
OBJECTIVES: To investigate the effectiveness and safety of tyrosine kinase inhibitors (TKIs) in the management of paediatric Philadelphia chromosome-positive acute lymphoblastic leukaemia (Ph+ALL). DESIGN: A systematic review and meta-analysis. DATA SOURCES: Electronic searches were conducted on CENTRAL, MEDLINE, EMBASE, SIOP, ASPHO, ASCO, ASH and four Chinese databases from inception to 8 March 2020. Language of publications was restricted in English and Chinese. ELIGIBILITY CRITERIA: Prospective and retrospective comparative studies were included. DATA EXTRACTION AND SYNTHESIS: Two authors independently assessed and extracted data. Quality of studies was assessed by the Cochrane Collaboration's tool and Newcastle-Ottawa Scale. Subgroup analysis was performed by comparing different types of TKIs. Quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation approach. RESULTS: Two randomised controlled trials (RCTs) and four cohort studies enrolling 536 patients were included. For RCTs, the pooled HR was 0.68 (95% CI 0.26 to 1.78) in overall survival (OS), 0.63 (95% CI 0.28 to 1.42) in event-free survival (EFS), respectively, comparing TKI arm with non-TKI arm for treatment of paediatric Ph+ALL. There was significant difference in OS and EFS between imatinib arm and dasatinib arm (HR 2.26, 95% CI 1.02 to 5.01; HR 2.36; 95% CI 1.27 to 4.39, respectively). For cohort studies, the pooled HR was 0.25 (95% CI 0.14 to 0.47) in OS, 0.25 (95% CI 0.12 to 0.56) in EFS, respectively, comparing TKI arm with non-TKI arm. There was no significance difference in adverse drug reaction between TKI group and without TKI group (risk ratio (RR) 0.82, 95% CI 0.63 to 1.08 in RCT; RR 1.01, 95% CI 0.64 to 1.59 in cohort studies; respectively), and imatinib versus dasatinib (RR 0.97, 95% CI 0.77 to 1.23). The quality of evidence was rated as low for OS, EFS and adverse drug reaction (ADR). CONCLUSIONS: The combination of TKIs with chemotherapy is likely to improve the OS and EFS rates in paediatric Ph+ALL, and dasatinib is superior than imatinib. Large sample size and prospective controlled studies are warranted. PROSPERO REGISTRATION NUMBER: CRD42018104107.
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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 | 0.003 | 0.005 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.026 | 0.006 |
| Bibliometrics | 0.001 | 0.004 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.002 |
| Research integrity | 0.001 | 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".