Allogeneic haematopoietic stem cell transplantation improves outcome of adults with relapsed/refractory Philadelphia chromosome-positive acute lymphoblastic leukemia entering remission following CD19 chimeric antigen receptor T cells

• Published in: Bone marrow transplantation (Basingstoke) 2021-01, Vol.56 (1), p.91-100
• Main Authors: Gu, Bin, Shi, Bing-Yu, Zhang, Xiang, Zhou, Shi-Yuan, Chu, Jian-Hong, Wu, Xiao-Jin, Fu, Cheng-Cheng, Qiu, Hui-Ying, Han, Yue, Chen, Su-Ning, Yu, Lei, Ma, Xiao, Wu, De-Pei
• Format: Article
• Language: English
• Subjects: 45/100; 631/250/251; 631/532/1542; Acute lymphoblastic leukemia; Acute lymphocytic leukemia; Adults; Antigen receptors, T cell; Antigens; B-cell receptor; Bone marrow; Care and treatment; CD19 antigen; Cell Biology; Chemotherapy; Chimeric antigen receptors; Chromosomes; Health aspects; Hematology; Hematopoietic stem cells; Internal Medicine; Leukemia; Lymphatic leukemia; Lymphocytes; Lymphocytes B; Lymphocytes T; Medical prognosis; Medicine; Medicine & Public Health; Minimal residual disease; Multivariate analysis; Philadelphia chromosome; Prognosis; Public Health; Receptors; Remission; Stem cell transplantation; Stem Cells; Survival; T cells; Transplantation
• ISSN: 0268-3369; 1476-5365
• DOI: 10.1038/s41409-020-0982-6

Relapsed/refractory Philadelphia chromosome-positive acute lymphoblastic leukemia (r/r Ph+ ALL) has an extremely poor prognosis. Chimeric antigen receptor T-cell (CART) therapy has acquired unprecedented efficacy in B-cell malignancies, but its role in the long-term survival of r/r Ph+ ALL patients is unclear. We analyzed the effect of CART on 56 adults with r/r Ph+ ALL who accepted split doses of humanized CD19-targeted CART after lymphodepleting chemotherapy. 51/56 (91.1%) achieved complete remission (CR) or CR with inadequate count recovery (CRi), including 38 patients with negative minimal residual disease (MRD) tested by bone marrow BCR-ABL1 copies. Subsequently, 30/51 CR/CRi patients accepted consolidative allogeneic haematopoietic stem cell transplantation (alloHSCT). Their outcomes were compared with those of 21/51 contemporaneous patients without alloHSCT. The 2-year overall survival (OS) and leukemia-free survival (LFS) of CR/CRi patients with alloHSCT were significantly superior to those without alloHSCT (58.9%, CI 49.8–68.0% vs. 22.7%, CI 12.7–32.7%, p  = 0.005; 53.2%, CI 43.6–62.8% vs. 18.8%, CI 9.2–28.4%, p  = 0.000, respectively). Multivariate analysis revealed that alloHSCT and MRD-negative post-CART were the independent prognostic factors for OS and LFS. CART therapy is highly effective for r/r Ph+ ALL patients, and consolidative alloHSCT could prolong their OS and LFS.