%A Accorsi Buttini,Eugenia %A Farina,Mirko %A Lorenzi,Luisa %A Polverelli,Nicola %A Radici,Vera %A Morello,Enrico %A Colnaghi,Federica %A Almici,Camillo %A Ferrari,Emilio %A Bianchetti,Andrea %A Leoni,Alessandro %A Re,Federica %A Bosio,Katia %A Bernardi,Simona %A Malagola,Michele %A Re,Alessandro %A Russo,Domenico %D 2023 %J Frontiers in Oncology %C %F %G English %K CAR T-cell therapy,myelodysplastic syndrome,diffuse large B cell lymphoma,next generation sequencing,Clonal hematopoiesis %Q %R 10.3389/fonc.2023.1036455 %W %L %M %P %7 %8 2023-January-20 %9 Case Report %+ Eugenia Accorsi Buttini,Unit of Blood Diseases and Bone Marrow Transplantation, Cell Therapies and Hematology Research Program, Department of Clinical and Experimental Science, University of Brescia, ASST Spedali Civili di Brescia,Italy,eugenia.accorsi@gmail.com %# %! HR-MDS following CAR T-cell therapy %* %< %T 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 %U https://www.frontiersin.org/articles/10.3389/fonc.2023.1036455 %V 13 %0 JOURNAL ARTICLE %@ 2234-943X %X BackgroundChimeric 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 presentationWe 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.ConclusionWe 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.