ArticleBlood2021
Investigation of product-derived lymphoma following infusion of piggyBac-modified CD19 chimeric antigen receptor T cells.
Article in Blood, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 149 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
149 citing papers in PubMed, 1 synthesis or guideline pooled it, 204 citations in OpenAlex.
- Mapping the clinical landscape of multifunctional CAR T cells: Targets, trends, and synergies.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Pooled it
- Donor-derived CARCIK-CD19 cells engineered with Sleeping Beauty transposon in acute lymphoblastic leukemia relapsed after allogeneic transplantation.Blood cancer journal · 2025Trial
- [The risk and management strategies for second primary tumor after CAR-T cell therapy].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2026Review
- Genomic features of clonal hematopoiesis-associated genes in primary and CAR T-cell-related secondary T-cell malignancies.Blood neoplasia · 2026Article
- Structure-based recasting of a mammalian DNA transpososome as an obligate heterodimer.bioRxiv : the preprint server for biology · 2026Article
- A guide to CAR T cell therapies: development, current status and future prospects.Nature reviews. Immunology · 2026Review
- Spectrum, pathobiology, mechanistic insights and diagnostic challenges of post-CAR T cell therapy lymphoproliferative disorders.Nature reviews. Clinical oncology · 2026Review
- The emerging roles of alternative splicing in modulating tumor immune responses and immunotherapies.Cell death and differentiation · 2026Review
- Review
- Emerging strategies to reduce the side effects of CAR-T cell therapy: focusing on gene editing and nanotechnology.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- CRISPR-Cas9 engineering of CAR-T cells: Can non-viral nanoparticles unlock safer and scalable genome editing?iScience · 2026Review
- Strategies to eliminate native T cell receptors for adoptive T cell therapies.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Review
- A Novel Strategy to Produce CAR-γδ T Cells via Site-Directed Gene Integration by a Combination of CRISPR/Cas9 and AAV.Cancer medicine · 2026Article
- Pathology associated with human CAR T cell administration in NOD.Cg-Veterinary pathology · 2026Article
- Secondary malignancy of T-cell origin after CAR T-cell therapy: EMA's conclusions from the evaluation of 38 suspected cases.Gene therapy · 2026Article
- Are we there yet? The road to faster and more efficient CAR T cell manufacturing.Journal of biological engineering · 2026Review
- Fine-tuning BACH2 dosage balances stemness and effector function to enhance antitumor T cell therapy.Nature immunology · 2026Article
- Beyond CAR-T and oncology: broadening chimeric antigen receptor technologies across cell types and diseases.Precision clinical medicine · 2026Review
- Position statement from the British Society of Blood and Marrow Transplantation and Cellular Therapy on insertional oncogenesis in gene-engineered advanced cell therapy products for treatment of haematological disorders.British journal of haematology · 2026Article
- In vivo engineering of CAR-T cells: delivery strategies and clinical translation.Biomarker research · 2026Review
89 more citing papers are in PubMed but not listed here.
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Authors and funding
20 authors at 6 institutions in 2 countries.
Funding
Abstract
We performed a phase 1 clinical trial to evaluate outcomes in patients receiving donor-derived CD19-specific chimeric antigen receptor (CAR) T cells for B-cell malignancy that relapsed or persisted after matched related allogeneic hemopoietic stem cell transplant. To overcome the cost and transgene-capacity limitations of traditional viral vectors, CAR T cells were produced using the piggyBac transposon system of genetic modification. Following CAR T-cell infusion, 1 patient developed a gradually enlarging retroperitoneal tumor due to a CAR-expressing CD4+ T-cell lymphoma. Screening of other patients led to the detection, in an asymptomatic patient, of a second CAR T-cell tumor in thoracic para-aortic lymph nodes. Analysis of the first lymphoma showed a high transgene copy number, but no insertion into typical oncogenes. There were also structural changes such as altered genomic copy number and point mutations unrelated to the insertion sites. Transcriptome analysis showed transgene promoter-driven upregulation of transcription of surrounding regions despite insulator sequences surrounding the transgene. However, marked global changes in transcription predominantly correlated with gene copy number rather than insertion sites. In both patients, the CAR T-cell-derived lymphoma progressed and 1 patient died. We describe the first 2 cases of malignant lymphoma derived from CAR gene-modified T cells. Although CAR T cells have an enviable record of safety to date, our results emphasize the need for caution and regular follow-up of CAR T recipients, especially when novel methods of gene transfer are used to create genetically modified immune therapies. This trial was registered at www.anzctr.org.au as ACTRN12617001579381.
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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.