Megakaryocyte aplastic thrombocytopeniaafter CAR T-cell therapy in a patient withmultiple myeloma:A case report

Chimeric antigen receptor(CAR)T-cell therapy is an effective new treatment strategy for hematologic malignancies.The success of CAR T-cell therapy in treating leukemia and lymphoma has promoted its development for multiple myeloma(MM),and the initial results of CAR T cell therapy have been encouraging.CAR T-cell therapy target antigens that have been clinically evaluated in MM;these antigens include CD19,B cell maturation antigen(BCMA),CD38,and CD138.A barrier to the widespread use of CAR T-cell therapy is its toxicity,primarily cytokine release syndrome(CRS),and neurologic toxicity.This study reports a patient with refractory MM who also developed megakaryocyte aplastic thrombocytopenia after receiving CAR T-cell therapy;such a case or the unusual side effects involving medications are yet unreported.There are risks in using cyclosporine and other immunosuppressants that may lead to MM recurrence as the use of such substances is contradictory to previous treatments;therefore,we temporarily administered platelet infusion as supportive care.Thus far,the condition of the patient has been steady and the patient regularly takes blood test in the hospital.

Boosting CAR-T cell therapy with CRISPR technology

Chimeric antigen receptor(CAR)-T cell therapy has made remarkable breakthroughs in treating cancers,especially hematologic malignancies,yet its broader application in cancer treatment is hindered by multiple challenges.Meanwhile,the development of clustered regularly interspaced short palindromic repeats(CRISPR)and its derived technologies has provided unprecedentedly efficient tools for genomic and cellular reprogramming,offering potential advantages for developing CAR-T cell therapy.There is hence a rapidly increasing interest in applying CRISPR to engineer CART cells.Here,we present a review of recent research utilizing CRISPR to boost CAR-T cell therapy by enhancing its safety or effectiveness.We first provide an overview of CAR-T cell therapy and CRISPR technology,followed by discussions on how CRISPR and its related technologies can be adopted to tackle various issues associated with CAR-T cell therapy,either via knockout/knockin of specific genes or CRISPR-based screening.We also summarize clinical trials involving CRISPR-edited CAR-T cells.Lastly,we address the potential risks of applying CRISPR in CAR-T cell engineering.