Frequent occurrence of CD19-negative relapse after CD19 CAR T and consolidation therapy in 14 TP53 -mutated r/r B-ALL children

摘要

Despite high remission rates after CD19 CAR T-celltherapy in patients with refractory or relapsed B acutelymphoblastic leukemia (r/r B-ALL), relapses were com-monly observed [1–4]. To improve long-term disease-freesurvival (DFS), our and other centers have conductedpost-CD19 CAR consolidations with allogeneic hemato-poietic stem cell transplantation (allo-HCT) or CD22CAR T-cell infusion [5–9]. However, some patients stillrelapsed, but it is unknown which factors caused theirrelapses. TP53 mutation predicts nonresponse and pooroutcome in childhood B-ALL during traditional therapies.Genomic instability caused by TP53 mutation inducesleukemia cells to undergo genomic evolution to survivestress and treatment [10–12]. In our previous studies,CAR T therapy can overcome genetic adverse features including TP53 mutation to induce remission [5, 6], butit is unknown whether the long-term outcome wouldbe influenced by TP53 mutation and other geneticaberrations.