ArticleBlood advances2022
Fludarabine exposure predicts outcome after CD19 CAR T-cell therapy in children and young adults with acute leukemia.
Article in Blood advances, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06879340 (A Phase 1 Multicenter, Open Label Trial Evaluating the Safety and Efficacy of DuoCAR20.19.22-D95 in Adult Patients With Relapsed or Refractory B-cell Malignancies), which is not on this map. Cited by 57 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Phase 1 Multicenter, Open Label Trial Evaluating the Safety and Efficacy of DuoCAR20.19.22-D95 in Adult Patients With Relapsed or Refractory B-cell Malignancies
Who cites it
57 citing papers in PubMed, 1 synthesis or guideline pooled it, 81 citations in OpenAlex.
- Pharmacokinetics and Pharmacodynamics of Systemic Corticosteroids in Autoimmune and Inflammatory Diseases: A Review of Current Evidence.Clinical pharmacokinetics · 2024Pooled it
- Minor histocompatibility antigen TCR-T.Blood advances · 2026Review
- Incorporating Immunotherapies into the Evolving Standard of Care for Pediatric B-Cell Precursor Acute Lymphoblastic Leukemia.Paediatric drugs · 2026Review
- Impact of fludarabine exposure on CAR T-cell outcomes in patients with large B-cell lymphoma.Blood advances · 2026Article
- Impact of fludarabine dosage on outcomes in large B-cell lymphoma patients treated with CAR T-cell therapy: a retrospective study of the CTIWP of the EBMT.Bone marrow transplantation · 2026Article
- TCM-derived immunometabolic modulators as systems adjuvants for CAR-T therapy in solid tumors: evidence hierarchy and translational roadmap.Journal of translational medicine · 2026Review
- Comparison of Fludarabine Versus Bendamustine as a Lymphodepleting Chemotherapy Prior to CAR-T for Large Cell Lymphoma.Transplantation and cellular therapy · 2026Article
- The evolving landscape of CAR T cell therapy in children and young adults with B cell acute lymphoblastic leukemia.Molecular therapy. Oncology · 2026Review
- Article
- Challenges and advances in CAR-T cell therapy for B-ALL.Biomarker research · 2026Review
- The quintessential role for CAR T cell therapy in children, adolescents and young adults with cancer.Nature reviews. Clinical oncology · 2026Review
- Physiologically Based Pharmacokinetic Virtual Twin Approach for Fludarabine Dosing in Pediatric Hematopoietic Stem Cell Transplantation.CPT: pharmacometrics & systems pharmacology · 2026Article
- Fludarabine dosing in the youngest children: safety first.Blood advances · 2026Article
- Cellular pharmacology of fludarabine: molecular determinants of transport and metabolism.Frontiers in pharmacology · 2026Review
- Towards Personalized Lymphodepletion: A Population Pharmacokinetic Fludarabine Model in Patients Receiving CAR T-Cell Therapy.Pharmaceutics · 2025Article
- International consensus guidelines for the conduct and reporting of CAR T-cell clinical trials in AML.Blood advances · 2025Article
- Significant matrix effect in fludarabine quantification in plasma: implications for CAR-T cell therapy monitoring.Bioanalysis · 2025Article
- Age-adjusted dosing of fludarabine for lymphodepletion in CAR T-cell therapy: a clinical trial simulation study.Blood advances · 2025Article
- Impact of fludarabine dose on outcome after allo-HSCT with reduced intensity conditioning for older patients with AML.Bone marrow transplantation · 2025Article
- Low Peripheral Blood Counts and Elevated Proinflammatory Cytokines Signal a Poor CD19 Chimeric Antigen Receptor T-cell Response in Acute Lymphoblastic Leukemia.Transplantation and cellular therapy · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
21 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The addition of fludarabine to cyclophosphamide as a lymphodepleting regimen prior to CD19 chimeric antigen receptor (CAR) T-cell therapy significantly improved outcomes in patients with relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL). Fludarabine exposure, previously shown to be highly variable when dosing is based on body surface area (BSA), is a predictor for survival in allogeneic hematopoietic cell transplantation (allo-HCT). Hence, we hypothesized that an optimal exposure of fludarabine might be of clinical importance in CD19 CAR T-cell treatment. We examined the effect of cumulative fludarabine exposure during lymphodepletion, defined as concentration-time curve (AUC), on clinical outcome and lymphocyte kinetics. A retrospective analysis was conducted with data from 26 patients receiving tisagenlecleucel for r/r B-ALL. Exposure of fludarabine was shown to be a predictor for leukemia-free survival (LFS), B-cell aplasia, and CD19-positive relapse following CAR T-cell infusion. Minimal event probability was observed at a cumulative fludarabine AUCT0-∞ ≥14 mg*h/L, and underexposure was defined as an AUCT0-∞ <14 mg*h/L. In the underexposed group, the median LFS was 1.8 months, and the occurrence of CD19-positive relapse within 1 year was 100%, which was higher compared with the group with an AUCT0-∞ ≥14 mg*h/L (12.9 months; P < .001; and 27.4%; P = .0001, respectively). Furthermore, the duration of B-cell aplasia within 6 months was shorter in the underexposed group (77.3% vs 37.3%; P = .009). These results suggest that optimizing fludarabine exposure may have a relevant impact on LFS following CAR T-cell therapy, which needs to be validated in a prospective clinical trial.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.