Unmanipulated haploidentical hematopoietic stem cell transplantation is an excellent option for children and young adult relapsed/refractory Philadelphia chromosome-negative B-cell acute lymphoblastic leukemia after CAR-T-cell therapy

• Published in: Leukemia Vol. 35; no. 11; pp. 3092 - 3100
• Main Authors: Hu, Guan-Hua, Zhao, Xiang-Yu, Zuo, Ying-Xi, Chang, Ying-Jun, Suo, Pan, Wu, Jun, Jia, Yue-Ping, Lu, Ai-Dong, Li, Ying-Chun, Wang, Yu, Jiao, Shun-Chang, Zhang, Long-Ji, Kong, Jun, Yan, Chen-Hua, Xu, Lan-Ping, Zhang, Xiao-Hui, Liu, Kai-Yan, Cheng, Yi-Fei, Zhang, Le-Ping, Huang, Xiao-Jun
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.11.2021; Nature Publishing Group
• Subjects: 13/100; 631/67/1990/283/2125; 692/699/1541/1990/283/2125; Acute lymphoblastic leukemia; Acute lymphocytic leukemia; Adolescent; Antigens; Cancer; Cancer Research; Care and treatment; Cell therapy; Cellular therapy; Child; Child, Preschool; Children; Chimeric antigen receptors; Chromosomes; Confidence intervals; Critical Care Medicine; Drug Resistance, Neoplasm; Female; Follow-Up Studies; Graft vs Host Disease - etiology; Graft vs Host Disease - pathology; Graft vs Host Disease - therapy; Graft-versus-host reaction; Hematology; Hematopoietic Stem Cell Transplantation - methods; Hematopoietic stem cells; Humans; Immunotherapy, Adoptive - adverse effects; Infant; Intensive; Internal Medicine; Leukemia; Leukemia in children; Lymphatic leukemia; Lymphoblastic leukemia in children; Lymphocytes B; Lymphocytes T; Lymphocytic leukemia in children; Male; Medicine; Medicine & Public Health; Neoplasm Recurrence, Local - pathology; Neoplasm Recurrence, Local - therapy; Oncology; Patient outcomes; Patients; Philadelphia Chromosome; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - pathology; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - therapy; Prognosis; Relapse; Remission; Remission (Medicine); Retrospective Studies; Salvage Therapy; Stem cell transplantation; Stem cells; Survival; Survival Rate; Therapy; Transplantation; Transplantation, Haploidentical; Young adults; China
• ISSN: 0887-6924; 1476-5551; 1476-5551
• DOI: 10.1038/s41375-021-01236-y

Although chimeric antigen receptor T-cell (CAR-T) therapy produces a high complete remission rate among patients with relapsed/refractory B-cell acute lymphoblastic leukemia, relapse remains an urgent issue. It is uncertain whether consolidative haploidentical-allogeneic hematopoietic stem cell transplantation (haplo-HSCT) is suitable for achieving sustainable remission. Therefore, we aimed to assess the efficacy and safety of bridging CAR-T therapy to haplo-HSCT. Fifty-two patients with relapsed/refractory Philadelphia chromosome-negative B-cell acute lymphoblastic leukemia who underwent haplo-HSCT after CAR-T therapy were analyzed. The median time from CAR-T therapy to haplo-HSCT was 61 days. After a median follow-up of 24.6 months, the 1-year probabilities of event-free survival, overall survival, and cumulative incidence of relapse were 80.1% (95% confidence interval (CI), 69.0–90.9), 92.3% (95% CI, 85.0–99.5), and 14.1% (95% CI, 10.7–17.4), respectively, while the corresponding 2-year probabilities were 76.0% (95% CI, 64.2–87.7), 84.3% (95% CI, 74.3–94.3), and 19.7% (95% CI, 15.3–24.0), respectively. No increased risk of 2-year cumulative incidence of graft-versus-host disease, treatment-related mortality, or infection was observed. A pre-HSCT measurable residual disease-positive status was an independent factor associated with poor overall survival (hazard radio: 4.201, 95% CI: 1.034–17.063; P  = 0.045). Haplo-HSCT may be a safe and effective treatment strategy to improve event-free survival and overall survival after CAR-T therapy.