ArticleGene therapy2018
Fludarabine and neurotoxicity in engineered T-cell therapy.
Article in Gene therapy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 50 papers, 3 of them syntheses that pooled it.
What it found
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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 1/2 Multicenter Study Evaluating the Safety and Efficacy of KTE-C19 in Adults With Refractory Aggressive Non-Hodgkin Lymphoma
A Phase 2, Single-arm, Multicenter Trial to Determine the Efficacy and Safety of JCAR015 in Adult Subjects With Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia
Who cites it
50 citing papers in PubMed, 3 syntheses or guidelines pooled it.
- Lymphodepleting chemotherapy practices and effect on safety and efficacy outcomes in patients with solid tumours undergoing T cell receptor-engineered T cell (TCR-T) Therapy: a systematic review and meta-analysis.Cancer immunology, immunotherapy : CII · 2023Pooled it
- Monitoring Neurocognitive Functioning After Pediatric Cellular Therapy or Hematopoietic Cell Transplant: Guidelines From the COG Neurocognition in Cellular Therapies Task Force.Transplantation and cellular therapy · 2022Guideline
- Effect of transplant status in CD19-targeted CAR T-cell therapy: a systematic review and meta-analysis.Medical oncology (Northwood, London, England) · 2018Pooled it
- Efficacy and safety of CD19 CAR T constructed with a new anti-CD19 chimeric antigen receptor in relapsed or refractory acute lymphoblastic leukemia.Journal of hematology & oncology · 2020Trial
- Neurological complications of current and emerging CAR-T cell therapies.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Review
- HosTIL territory: mapping the landscape of toxicity in TIL therapy.Journal for immunotherapy of cancer · 2026Review
- mRNA engineering of allogeneic mesenchymal stem cells enables coordinated delivery of T cell engagers and immunotherapeutic cues.Nature biomedical engineering · 2026Article
- Delayed fatal neurotoxicity in post CAR-T cell therapy for multiple myeloma, a case report.Leukemia research reports · 2026Article
- Chimeric Antigen Receptor T-Cell Therapy in Dialysis-Dependent Patients With Multiple Myeloma: Insights From a 5-Case Series.Kidney medicine · 2025Article
- Research progress on chimeric antigen receptor-based immunotherapy against autoimmune diseases.Human vaccines & immunotherapeutics · 2025Review
- Neuroimaging Findings in Children and Young Adults With Neurotoxicity After CAR T-Cell Therapy for B-Cell Malignancies.Neurology · 2025Article
- Lymphodepletion chemotherapy in chimeric antigen receptor-engineered T (CAR-T) cell therapy in lymphoma.Bone marrow transplantation · 2025Review
- CD19 -targeted CAR T therapy treating hematologic malignancies: hidden danger is the next neighbor to security?Frontiers in immunology · 2025Review
- The impact of age and renal function on the pharmacokinetics and protein binding characteristics of fludarabine in paediatric and adult patients undergoing allogeneic haematopoietic stem cell transplantation conditioning.European journal of clinical pharmacology · 2024Article
- Impact of diagnostic investigations in the management of CAR T-cell-associated neurotoxicity.Blood advances · 2024Article
- Stealth transgenes enable CAR-T cells to evade host immune responses.Journal for immunotherapy of cancer · 2024Article
- Her2 amplification, Rel-A, and Bach1 can influence APOBEC3A expression in breast cancer cells.PLoS genetics · 2024Article
- Bendamustine lymphodepletion is a well-tolerated alternative to fludarabine and cyclophosphamide lymphodepletion for axicabtagene ciloleucel therapy for aggressive B-cell lymphoma.American journal of hematology · 2023Article
- Challenges of Anti-Mesothelin CAR-T-Cell Therapy.Cancers · 2023Review
- Targeting myeloid-derived suppressor cells with gemcitabine to enhance efficacy of adoptive cell therapy in bladder cancer.Frontiers in immunology · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Adoptive T-cell therapy, incorporating engineered T cell receptors (TCRs) or chimeric antigen receptors (CARs), target tumor antigens with high affinity and specificity. To increase the potency of adoptively transferred T cells, patients are conditioned with lymphodepleting chemotherapy regimens prior to adoptive T-cell transfer (ACT), and data suggest that fludarabine is an important component of an effective regimen. In a recent clinical trial using CAR-T cells engineered to target the CD19 B-cell antigen to treat acute lymphoblastic leukemia, JCAR-015 (NCT02535364), two patient deaths due to cerebral edema led to trial suspension. The lymphodepleting agent fludarabine was suggested as the causative agent, in part due to its known association with neurotoxicity and its ability to induce greater potency. In a similar CAR-T study also incorporating fludarabine in the preconditioning regimen, ZUMA-1 (NCT02348216), one patient died of cerebral edema. However, subsequent deaths in the JCAR-015 study after removal of fludarabine and improved understanding behind the mechanisms of CAR-T-related encephalopathy syndrome (CRES) indicate that fludarabine is not the primary causative agent of cerebral edema and that it can be safely incorporated into the preconditioning regimen for ACT. Since entering clinical use in the late 1980s as a chemotherapy agent, fludarabine and similar analogs have been associated with lethal neurological toxicity, yet the manifestation and timing of symptoms are distinct to those observed recently in ACT. Herein, we review the history of fludarabine development as a chemotherapeutic agent, and discuss the safety of its continued use in preconditioning regimens for ACT.
Indexed as
Identifiers
29789639What 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.