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

Eugenia Accorsi Buttini; Mirko Farina; Luisa Lorenzi; Nicola Polverelli; Vera Radici; Enrico Morello; Federica Colnaghi; Camillo Almici; Emilio Ferrari; Andrea Bianchetti; Alessandro Leoni; Federica Re; Katia Bosio; Simona Bernardi; Michele Malagola; Alessandro Re; Domenico Russo

doi:10.3389/fonc.2023.1036455

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

Front Oncol. 2023 Jan 20:13:1036455. doi: 10.3389/fonc.2023.1036455. eCollection 2023.

Authors

Eugenia Accorsi Buttini¹, Mirko Farina¹, Luisa Lorenzi², Nicola Polverelli¹, Vera Radici¹, Enrico Morello¹, Federica Colnaghi¹, Camillo Almici³, Emilio Ferrari³, Andrea Bianchetti³, Alessandro Leoni^{1

4}, Federica Re^{1

4}, Katia Bosio^{1

4}, Simona Bernardi^{1

4}, Michele Malagola¹, Alessandro Re⁵, Domenico Russo¹

Affiliations

¹ 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, Brescia, Italy.
² Department of Molecular and Translational Medicine, Section of Pathology, University of Brescia, ASST Spedali Civili di Brescia, Brescia, Italy.
³ Stem Cell Laboratory, Section of Hematology and Blood Coagulation, Clinical Chemistry Laboratory, Diagnostics Department, ASST Spedali Civili di Brescia, Brescia, Italy.
⁴ Research Center Ail (CREA), Chair of Hematology Department of Clinical and Experimental Science, University of Brescia, ASST Spedali Civili di Brescia, Brescia, Italy.
⁵ Hematology Unit, ASST Spedali Civili di Brescia, Brescia, Italy.

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.

Keywords: CAR T-cell therapy; clonal hematopoiesis; diffuse large B cell lymphoma; myelodysplastic syndrome; next generation sequencing.

Publication types

Case Reports