Response to Front-Line Imatinib Treatment in Children and Adolescents with CML - Data from a Large Pediatric Cohort
Bibliographic record
Abstract
Abstract Purpose Results of the prospective trial "CML-PAED-II" assessing treatment efficacy and side effects in children and adolescents with newly diagnosed chronic myeloid leukemia (CML) are reported. Patients and Methods 156 patients (age range 1.3-18.0 years, 91 male) with newly diagnosed CML (N= 146 chronic phase (CML-CP), N= 3 accelerated phase (CML-AP), N= 7 blastic phase (CML-BP)) received imatinib upfront (300 mg/m², 400 mg/m², 500 mg/m², respectively). Therapy response, progression-free survival, causes of treatment failure and proportion of patients undergoing stem cell transplantation were analyzed in 148 patients with complete data. Results Event-free survival rate at 18 months for pediatric patients diagnosed in CML-CP (median follow-up time 25 months, range: 0.1-120) was 97% (95% CI, 94.2%-99.9%). According to the 2006 ELN-criteria complete hematologic response at month 3, complete cytogenetic response (CCyR) at month 12, and molecular response (MR3.0) at month 18 were achieved in 98%, in 63%, and 59% of the patients, respectively. At month 36 on continuous first line imatinib or 2nd generation tyrosine kinase inhibitor treatment, 86% of the patients achieved CCyR and 74% achieved MR3.0. 66% of the patients experienced at least one side effect. Imatinib-related anemia was the most frequent toxicity observed if all grades were considered (N=98; 66%) while neutropenia was the most frequently reported grade 3/4 hematologic adverse effect (N=22; 15%). Among non-hematologic toxicities, all grades of gastrointestinal toxicity were observed most frequently (N=57, 38%), however, it occurred at lower grades 1/2 in all but one patient. Higher grade 3/4 musculoskeletal pain was also frequent (N=53, 36%). Twenty-seven patients (18%) had to discontinue treatment temporarily while nine patients permanently terminated imatinib due to non-tolerable side effects (neutropenia N= 4, muscle cramps N= 3, skin N= 1, liver N= 1). Thirty-eight patients (27%) experienced imatinib failure because of unsatisfactory response (N= 27) or intolerance (N= 9). 28/148 patients (19%) underwent stem cell transplantation (SCT). In the SCT sub-cohort 2/23 patients diagnosed in CML-CP, 0/1 in CML-AP, and 2/4 in CML-BP, respectively, died of relapse (N=3) or SCT-related complications (N=2). Conclusion This large pediatric trial provides evidence confirming that first line imatinib in children is highly effective. Observed adverse effects are acceptable and mainly comprise hematological side effects. Long term outcome and effects of a potentially life-long TKI treatment have to be registered in cooperation with adult hematologists in extended surveillance follow-up studies. Disclosures Suttorp: Novartis: Research Funding. Schrappe: JAZZ Pharma: Consultancy, Research Funding; Baxalta: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; SigmaTau: Consultancy, Research Funding; Medac: Consultancy, Research Funding. Thiede: Novartis: Consultancy, Speakers Bureau; Bayer: Consultancy, Speakers Bureau; Roche: Consultancy; Agendix: Employment.
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 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 | 0.001 |
| 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) | 0.001 | 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".