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
National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China.
Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, 215006, China.
Bone Marrow Transplant. 2021 Jan;56(1):91-100. doi: 10.1038/s41409-020-0982-6. Epub 2020 Jun 24.
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.
复发/难治性费城染色体阳性急性淋巴细胞白血病（r/r Ph+ ALL）的预后极差。嵌合抗原受体T细胞（CART）疗法在B细胞恶性肿瘤中取得了前所未有的疗效，但其在r/r Ph+ ALL患者长期生存中的作用尚不清楚。我们分析了CART对56例接受淋巴细胞清除化疗后分剂量使用人源化CD19靶向CART的r/r Ph+ ALL成年患者的影响。51/56（91.1%）例患者达到完全缓解（CR）或血细胞计数恢复不全的CR（CRi），其中38例患者经骨髓BCR-ABL1拷贝检测微小残留病（MRD）为阴性。随后，30/51例CR/CRi患者接受了巩固性异基因造血干细胞移植（alloHSCT）。将他们的结局与同期未接受alloHSCT的21/51例患者的结局进行比较。接受alloHSCT的CR/CRi患者的2年总生存（OS）率和无白血病生存（LFS）率显著优于未接受alloHSCT的患者（分别为58.9%，CI 49.8 - 68.0%对22.7%，CI 12.7 - 32.7%，p = 0.005；53.2%，CI 43.6 - 62.8%对18.8%，CI 9.2 - 28.4%，p = 0.000）。多因素分析显示，alloHSCT和CART治疗后MRD阴性是OS和LFS的独立预后因素。CART疗法对r/r Ph+ ALL患者非常有效，巩固性alloHSCT可延长其OS和LFS。
