Exploring the Dilemma of Allogeneic Hematopoietic Cell Transplantation after Chimeric Antigen Receptor T Cell Therapy: To Transplant or Not?

Patients with refractory or relapsed (R/R) B cell acute lymphoblastic leukemia (B-ALL) and highly aggressive B cell non-Hodgkin lymphoma (B-NHL) have a very dismal prognosis and limited treatment options. The advent of chimeric antigen receptor (CAR) T cell therapy constitutes a milestone in current cell and gene therapies, covering the unmet need of treatment of high-risk patients and bringing immunotherapies one step closer toward cancer therapeutics, including hematologic malignancies. CAR T cells targeting CD19 antigen have shown startling remission rates in heavily pretreated B-ALL and B-NHL patients, in whom CAR T cell therapy may sometimes be their last-resort treatment. However, a high proportion of these patients evade immune surveillance by CAR T cells losing their initial deep responses, which leads to disease recurrence as either CD19-positive or CD19-negative relapse. As a result, many investigators have questioned the need for consolidative allogeneic hematopoietic stem cell transplantation (allo-HCT) after CAR T cell therapy, once a patient has achieved remission. There remains much controversy regarding whether CAR T cells should be a bridge therapy to allo-HCT or a definitive treatment, owing to the paucity of strong evidence-based data. In this context, here we review the existing data regarding the necessity, safety, and outcomes of allo-HCT performed after autologous anti-CD19 CAR T cell therapy in B-ALL and B-NHL patients.