Consolidative allogeneic hematopoietic stem cell transplantation after chimeric antigen receptor T-cell therapy for rela
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Consolidative allogeneic hematopoietic stem cell transplantation after chimeric antigen receptor T-cell therapy for relapsed/refractory B-cell acute lymphoblastic leukemia: who? When? Why? Huiwen Jiang1,2, Yu Hu1,2 and Heng Mei1,2*
Abstract Although anti-CD19 chimeric antigen receptor (CAR) T-cell therapy shows good efficacy in patients with relapsed/ refractory B-cell acute lymphoblastic leukemia (r/r B-ALL), it fails to improve long-term leukemia-free survival (LFS). Allogeneic hematopoietic stem cell transplantation (allo-HSCT) after CAR T-cell therapy has emerged as a promising strategy to prolong LFS. Nevertheless, which patients are likely to benefit from consolidative allo-HSCT, as well as the optimal therapeutic window, remain to be explored. Recent clinical data indicate that patients with complex karyotypes, adverse genes, and high pre-infusion minimal residual disease (MRD) by flow cytometry in the bone marrow, were at high risk of relapse after CAR T-cell therapy. High pre-lymphodepletion lactate dehydrogenase, low prelymphodepletion platelet count, absence of fludarabine in lymphodepletion, persistent leukemic sequence by high throughput sequencing in bone marrow after CAR T-cell infusion, and early loss of CAR T cells have also been linked to relapse after CAR T-cell therapy. In patients having these risk factors, consolidative allo-HSCT after CAR T-cell therapy may prolong LFS. Allo-HSCT provides optimal clinical benefit in patients with MRD-negative complete remission, typically within three months after CAR T-cell therapy. Herein, we summarize the clinical data on consolidative allo-HSCT after anti-CD19 CAR T-cell therapy, as well as the potential factors associated with allo-HSCT benefit. We also discuss the optimal therapeutic window and regimen of consolidative allo-HSCT. Finally, and most importantly, we provide recommendations for the assessment and management of r/r B-ALL patients undergoing anti-CD19 CAR T-cell therapy. Keywords: Chimeric antigen receptor-modified T-cell therapy, Allogeneic hematopoietic stem cell transplantation, Relapsed or refractory B-cell acute lymphoblastic leukemia, Prognosis
* Correspondence: [email protected] 1 Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China 2 Hubei Clinical Medical Center of Cell Therapy for Neoplastic Disease, Wuhan 430022, China
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