达沙替尼
医学
微小残留病
内科学
化疗
累积发病率
造血干细胞移植
急性淋巴细胞白血病
胃肠病学
伊马替尼
费城染色体
移植
肿瘤科
化疗方案
外科
白血病
淋巴细胞白血病
髓系白血病
染色体易位
化学
生物化学
基因
作者
J.-H. Yoon,Ho‐Young Yhim,Jae‐Yong Kwak,Jae‐Sook Ahn,Deok‐Hwan Yang,J.-J. Lee,Se Joo Kim,J.-S. Kim,S.J. Park,Chul Won Choi,Hyeon‐Seok Eom,S.-K. Park,Soo Young Choi,S.-H. Kim,D.-W. Kim,S. Lee
标识
DOI:10.1093/annonc/mdw123
摘要
The use of imatinib combined with chemotherapy has demonstrated improved outcome in adults with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-positive ALL). However, a substantial proportion of patients continue to die as a result of disease progression.We assessed the minimal residual disease (MRD)-based effect and long-term outcome of first-line incorporation of dasatinib (100 mg once daily) into chemotherapy alternatively for adults with Ph-positive ALL. The primary end point was the major molecular response (MMR) rate by the end of the second dasatinib cycle. Patients with a donor proceeded to allogeneic stem cell transplantation (SCT) as early as possible. MRD monitoring was centrally evaluated by real-time quantitative polymerase chain reaction (4.5-log sensitivity) using bone marrow samples.Fifty-one patients (median age, 46 years) were enrolled and treated with this strategy. After the first dasatinib cycle, 50 patients (98.0%) achieved complete remission (CR). By the end of the second dasatinib cycle, 46 (93.9%) of 49 assessable patients had persistent CR, and 38 (77.6%) had MMR (32.7%) or undetectable MRD (44.9%). On the basis of the MRD kinetics by this time point, the numbers of early-stable, late, and poor molecular responders were 23 (46.9%), 15 (30.7%), and 11 (22.4%), respectively. Thirty-nine patients (76.5%) underwent allogeneic SCT in CR1. After a median follow-up of 54 months, the 4-year cumulative incidence of relapse and disease-free survival (DFS) rate for all patients were 30.0% and 52.0%, respectively, and the corresponding outcomes among those receiving allogeneic SCT in CR1 were 20.5% and 64.1%, respectively. Poor molecular responders had a higher risk of relapse and DFS than those of early-stable molecular responders.This dasatinib-based protocol was effective for achieving a good quality molecular response and durable DFS in adults with Ph-positive ALL.clinicaltrials.gov, NCT01004497.
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