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- Title
High risk-myelodysplastic syndrome following CAR T-cell therapy in a patient with relapsed diffuse large B cell lymphoma: A case report and literature review.
- Authors
Buttini, Eugenia Accorsi; Farina, Mirko; Lorenzi, Luisa; Polverelli, Nicola; Radici, Vera; Morello, Enrico; Colnaghi, Federica; Almici, Camillo; Ferrari, Emilio; Bianchetti, Andrea; Leoni, Alessandro; Re, Federica; Bosio, Katia; Bernardi, Simona; Malagola, Michele; Re, Alessandro; Russo, Domenico
- Abstract
Background: Chimeric antigen receptor (CAR) T-cell therapy represents the most advanced immunotherapy against relapsed/refractory B cell malignancies. While cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome are distinctive, known CAR T-cell acute adverse events, hematological toxicity has been increasingly reported. Cytopenia following CAR T-cell treatment is attributed in most cases to lymphodepletion regimens, bridging chemotherapy, or radiotherapy. However, when cytopenia becomes prolonged, the development of myelodysplastic syndrome (MDS) should be considered. Case presentation: We report a case of high risk (HR)-MDS following CAR T-cell therapy in a patient with relapsed diffuse large B cell lymphoma. Eight months after CAR T-cell infusion, the blood count showed progressive, worsening cytopenia and the bone marrow biopsy revealed multilineage dysplasia without excess of blasts associated with chromosome 7 deletion and RUNX1 mutation. Next generation sequencing analysis, retrospectively performed on stored samples, showed a germ line CSF3R mutation, CEBPA clonal hematopoiesis, but no RUNX1 lesion. Conclusion: We describe a case of HR-MDS, with deletion of chromosome 7 and acquisition of RUNX1 mutation, developing after CAR T-cell therapy in a patient with clonal hematopoiesis (CH). Previous chemotherapy favored MDS onset; however, we could not exclude the fact that the impairment of immunosurveillance related to either lymphodepletion or CAR T-cell infusion may play a role in MDS development. Thus, we designed a multicenter prospective study (ClonHema-CAR-T-Study) to investigate if cytopenia after CAR T-cell treatment may be due to underling CH as well as the presence of secondary myeloid malignancies.
- Subjects
DIFFUSE large B-cell lymphomas; B cell lymphoma; NUCLEOTIDE sequencing; T cells; CHIMERIC antigen receptors; CYTOKINE release syndrome
- Publication
Frontiers in Oncology, 2023, Vol 13, p1
- ISSN
2234-943X
- Publication type
Article
- DOI
10.3389/fonc.2023.1036455