Secondary haematological dysplasia after CAR-T-cell therapy for acute lymphoblastic leukaemia in children

Abstract

The use of CAR-T is becoming more widespread in the treatment of haematological malignancies. In adults, secondary myelodysplastic syndromes (MDS) after CAR-T have been described. However, there are currently no data on the risk of MDS following CAR-T in children treated for acute lymphoblastic leukaemia (ALL). We studied all children treated with CAR-T cells at Hospital Sant Joan de Déu in Barcelona and those with persistent cytopenias were evaluated at the cytological, cytogenetic, and molecular levels to look for MDS. A total of 106 patients received CAR-T for ALL. Among 40 patients without early relapse or subsequent therapy after CAR-T, four fulfilled the WHO criteria for myelodysplasia. These four patients had received a haematopoietic stem cell transplantation (HSCT) prior to CAR-T and presented cytopenias with severe dysplastic changes in bone marrow after CAR-T. One patient had clonal MDS with high-risk cytogenetics arising from the host cells requiring a HSCT. Three patients had non-progressive dysplasia arising from the donor cells. Two are alive in complete remission with stable cytopenias and one succumbed to ALL relapse. This is the first description of post-CAR-T MDS and haematological dysplasia in children and highlights the need to monitor children with persistent post-CAR-T cytopenias.