Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8429998 | Biology of Blood and Marrow Transplantation | 2018 | 34 Pages |
Abstract
Here we compare outcomes between the tyrosine kinase inhibitors (TKIs) plus chemotherapy regimen and allogeneic hematopoietic stem cell transplantation (transplantation cohort) in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+âALL) and explore factors associated with prognosis. Data from 145 Ph+âALL patients were analyzed retrospectively. Patients were treated with imatinib plus chemotherapy and then transplantation or continuous TKIs with chemotherapy based on patient preference. A total of 145 Ph+âALL patients were recruited for this study (median age, 37 years; range, 14 to 65). Among these patients, 81 were men (55.9%) and 86 underwent IKZF1 detection, which identified 59 patients (68.6%) with IKZF1 deletions. After treatment 136 patients (95.8%) achieved complete remission (CR) eventually. With a median follow-up of 33 months (range, 4 to 114) for CR patients, 77 patients (57.9%) underwent transplantation and 56 (42.1%) received continuous TKIs with chemotherapy. At the 4-year follow-up the cumulative incidence of relapse (CIR), disease-free survival (DFS), and overall survival (OS) were 29.4% (95% confidence interval [CI], 24.9% to 34.4%), 60.9% (95% CI, 56.5% to 65.3%), and 69.2% (95% CI, 65.1% to 73.3%), respectively. Multivariate analysis showed that WBCâcounts <â30âÃâ109/L at diagnosis (hazard ratio [HR], 4.2; 95% CI, 1.9 to 9.2; Pââ<â.001; HR, 2.6; 95% CI, 1.4 to 4.9; Pâ=â.003; HR, 2.7; 95% CI, 1.4 to 5.4; Pâ=â.003), 3-log reduction of BCR-ABL levels from baseline after 2 consolidation cycles (HR, 4.4; 95% CI, 1.9 to 9.9; Pâ<â.001; HR, 3.1; 95% CI, 1.7 to 5.9; Pâ <â.001; HR, 3.5; 95% CI, 1.9 to 8.7; Pâ=â.001; defined as “minimal residual disease low level”), and transplantation (HR, 5.0; 95% CI, 2.2 to 11.2; Pââ<â.001; HR, 3.3; 95% CI, 1.7 to 6.4; Pâââ<â.001; HR, 4.1; 95% CI, 1.9 to 8.7; Pâââ<â.001) were the favorable factors of CIR, DFS, and OS. According to the first 2 risk factors, CR patients were divided into 3 groups: low risk (no factor, nâ=â42, 31.6%), intermediate risk (1 factor, nâ=â73, 54.9%), and high risk (2 factors, nâ=â18, 13.5%). In the low-risk group at the 4-year follow up no significant difference existed between the transplant and nontransplant arms for the probabilities of CIR (8.5% versus 7.7%, Pâ=â.671), DFS (88.2% versus 83.9%, Pâ=â.426), and OS (96.6% versus 83.3%, Pâ=â.128). In the intermediate- and high-risk groups at the 4-year follow-up, CIR (23.6% versus 36.9%, Pâ=â.017; 37.5% versus 100.0%, Pâââ<.001), DFS (62.4% versus 43.8%, Pâ=â.048; 56.2% versus 0%, Pâââ<.001), and OS (76.1% versus 47.7%, Pâ=â.037; 51.4% versus 6.3%, Pâ=â.001) rates were significantly better in the transplant arm than in the nontransplant arm. In surviving patients of the low-risk group, no difference in complete molecular response (CMR) rates (85.7% versus 72.7%, Pâ=â.379) between the transplant and nontransplant arms was found. However, in the intermediate-risk group the proportion of CMR was significantly higher in the transplant arm than in the nontransplant arm (82.8% versus 42.9%, Pâ=â.006). In the high-risk group 4 of 7 transplant patients (57.1%) were in CMR, and no patients survived in the nontransplant arm. Allogeneic hematopoietic stem cell transplantation confers significant survival advantages for Ph+âALL patients compared with TKIs plus chemotherapy, especially in intermediate- and high-risk patients.
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Authors
Jing Wang, Qian Jiang, Lan-ping Xu, Xiao-Hui Zhang, Huan Chen, Ya-Zhen Qin, Guo-rui Ruan, Hao Jiang, Jin-song Jia, Ting Zhao, Kai-Yan Liu, Bin Jiang, Xiao-Jun Huang,