Minimal residual disease-based effect and long-term outcome of first-line dasatinib combined with chemotherapy for adult Philadelphia chromosome-positive acute lymphoblastic leukemia
- Authors
- Yoon, J. -H.; Yhim, H. -Y.; Kwak, J. -Y.; Ahn, J. -S.; Yang, D. -H.; Lee, J. -J.; Kim, S. -J.; Kim, J. -S.; Park, S. J.; Choi, C. W.; Eom, H. -S.; Park, S. -K.; Choi, S. -Y.; Kim, S. -H.; Kim, D. -W.; Lee, S.
- Issue Date
- Jun-2016
- Publisher
- Oxford University Press
- Keywords
- minimal residual disease; dasatinib; Philadelphia chromosome; acute lymphoblastic leukemia; allogeneic stem cell transplantation
- Citation
- Annals of Oncology, v.27, no.6, pp 1081 - 1088
- Pages
- 8
- Journal Title
- Annals of Oncology
- Volume
- 27
- Number
- 6
- Start Page
- 1081
- End Page
- 1088
- URI
- https://scholarworks.bwise.kr/sch/handle/2021.sw.sch/9106
- DOI
- 10.1093/annonc/mdw123
- ISSN
- 0923-7534
1569-8041
- Abstract
- Background: 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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