期刊
NATURE MEDICINE
卷 28, 期 4, 页码 713-+出版社
NATURE PORTFOLIO
DOI: 10.1038/s41591-022-01702-9
关键词
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资金
- Damon Runyon Physician-Scientist Award
- Burroughs Wellcome Fund Postdoctoral Enrichment Program
- American Society of Hematology-Robert Wood Johnson Foundation
- Harold Amos Medical Faculty Development Program
- Fauci Fellowships - National Italian American Foundation
- Mario Luvini fellowship grant - Fondazione Ticinese per la Ricerca sul Cancro
- National Cancer Institute (NCI) [K08CA194256]
- Lymphoma Research Foundation (LRF) Career Development Award
- Gilead Research Scholar Award
- Gabrielle's Angel Foundation
- Emerson Collective Award
- Laffey-McHugh Foundation
- Berman and Maguire Funds for Lymphoma Research at the University of Pennsylvania
- NCI [1K99CA212302, R00CA212302]
- Center for Precision Medicine Accelerator Award [1R01CA219871-01A1]
- University of Pennsylvania-Novartis Alliance
- Scholar in Clinical Research award from the Leukemia and Lymphoma Society
- American-Italian Cancer Foundation Postdoctoral Research Fellowship
- Associazione Italiana contro le Leucemie-Linfomi e Mieloma Milano e Provincia Organizzazione Non Lucrativa di Utilita Sociale
- National Institutes of Health/NCI MSK Cancer Center Support Grant [P01 CA23766, P30 CA008748]
- LRF Postdoctoral Fellowship Grant
- Parker Institute for Cancer Immunotherapy
- Starr Cancer Consortium
- Tri-Institutional Stem Cell Initiative
- Lymphoma Foundation
- Susan and Peter Solomon Divisional Genomics Program
- Cycle for Survival
- [1P01CA214278]
- [R01CA226983]
- [K08HL143189]
- [R01-CA228358]
- [R01-CA228308]
- [R01-HL147584]
- [P01-CA023766]
- [R01-HL125571]
- [R01-HL123340]
- [P01-AG052359]
This study investigated the changes in the intestinal microbiome of patients with B cell lymphoma and leukemia after receiving anti-CD19 CAR T cell therapy, and found that these changes are associated with clinical outcomes.
Anti-CD19 chimeric antigen receptor (CAR) T cell therapy has led to unprecedented responses in patients with high-risk hematologic malignancies. However, up to 60% of patients still experience disease relapse and up to 80% of patients experience CAR-mediated toxicities, such as cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome. We investigated the role of the intestinal microbiome on these outcomes in a multicenter study of patients with B cell lymphoma and leukemia. We found in a retrospective cohort (n = 228) that exposure to antibiotics, in particular piperacillin/tazobactam, meropenem and imipenem/cilastatin (P-I-M), in the 4 weeks before therapy was associated with worse survival and increased neurotoxicity. In stool samples from a prospective cohort of CAR T cell recipients (n = 48), the fecal microbiome was altered at baseline compared to healthy controls. Stool sample profiling by 16S ribosomal RNA and metagenomic shotgun sequencing revealed that clinical outcomes were associated with differences in specific bacterial taxa and metabolic pathways. Through both untargeted and hypothesis-driven analysis of 16S sequencing data, we identified species within the class Clostridia that were associated with day 100 complete response. We concluded that changes in the intestinal microbiome are associated with clinical outcomes after anti-CD19 CAR T cell therapy in patients with B cell malignancies.
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