Clinical responses in pediatric patients with relapsed/refractory leukemia treated with azacitidine and venetoclax
Bibliographic record
Abstract
Clinical responses in pediatric patients with relapsed/refractory leukemia treated with azacitidine and venetoclaxDespite optimization and escalation of risk-based chemotherapy regimens, children with relapsed or chemotherapyrefractory acute leukemias, particularly acute myeloid leukemia (AML), remain difficult to cure. 1,2Traditional intensive cytotoxic chemotherapy salvage regimens require extended inpatient hospitalization due to infectious risk during severe myelosuppression and are accompanied by therapy-related morbidity and deleterious impact upon quality-of-life. 3,4The combination of the hypomethylating agent azacitidine with venetoclax, an oral selective BH3mimetic inhibitor of the anti-apoptotic protein B-cell lymphoma 2 (BCL-2), is effective at remission induction in elderly or intensive induction chemotherapy-ineligible adults with previously-untreated AML and is Food and Drug Administration-approved for this indication. 5,6The recent VENAML phase I clinical trial demonstrated safety and activity of venetoclax combined with idarubicin and/or highdose cytarabine in children and adolescents/young adults (AYAs) with relapsed refractory AML (clinicaltrials gov.Identifier: NCT03194932). 7However, clinical experience with the azacitidine/venetoclax regimen in children has been limited to small case series. 8,9Herein, we report clinical characteristics and outcomes of 37 pediatric patients with relapsed/refractory acute leukemias treated at our institution with commercially-available azacitidine/venetoclax therapy.We analyzed data from patients aged 0-21 years with multiply-relapsed/refractory acute lymphoblastic leukemia (ALL), AML, or mixed-phenotype acute leukemia (MPAL) treated with azacitidine/venetoclax without or with the CD33 antibody-drug conjugate gemtuzumab ozogamicin (GO) at the Children's Hospital of Philadelphia from January 1 st , 2018 to March 31 st , 2022.Institutional Review Board exemption was obtained for retrospective chart review.Clinical data were abstracted from electronic medical records on baseline patient demographics, leukemia-associated immunophenotyping and genetic characteristics, therapy administration, clinical response, and post-azacitidine/venetoclax outcomes with clinical follow-up through June 30, 2022.Azacitidine 100 mg/m 2 daily was given intravenously on days 1-5 of each 28-day cycle.Venetoclax was given once daily as oral tablets (swallowed intact or crushed) with 3day 'ramp-up' dosing during cycle 1 to minimize tumor lysis syndrome (TLS) risk with body surface area-adjusted adult exposure-equivalent dosing (AED) of 200 mg (day 1),
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.002 | 0.005 |
| 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; both teacher heads agree on what is shown here.
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".