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
Annals of oncology : official journal of the European Society for Medical Oncology / ESMO
2016Jun ; 27 ( 6 ) :1081-8.
PMID : 26951627
ÀúÀÚ »ó¼¼Á¤º¸
Yoon, J-H - Department of Hematology, Catholic BMT Center Leukemia Research Institute, College of Medicine, The Catholic University of Korea, Seoul.
Yhim, H-Y - Division of Hematology-Oncology, Department of Internal Medicine, Chonbuk National University Medical School, Jeonju.
Kwak, J-Y - Division of Hematology-Oncology, Department of Internal Medicine, Chonbuk National University Medical School, Jeonju.
Ahn, J-S - Department of Hematology-Oncology, Chonnam National University Hwasun Hospital, Jeollanamdo.
Yang, D-H - Department of Hematology-Oncology, Chonnam National University Hwasun Hospital, Jeollanamdo.
Lee, J-J - Department of Hematology-Oncology, Chonnam National University Hwasun Hospital, Jeollanamdo.
Kim, S-J - Division of Hematology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul.
Kim, J-S - Division of Hematology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul.
Park, S J - Division of Hematology-Oncology, Department of Internal Medicine, Korea University School of Medicine, Seoul.
Choi, C W - Division of Hematology-Oncology, Department of Internal Medicine, Korea University School of Medicine, Seoul.
Eom, H-S - Hematologic Oncology Clinic, Center for Specific Organs Center, National Cancer Center, Goyang.
Park, S-K - Division of Hematology-Oncology, Department of Internal Medicine, Soonchunhyang University School of Medicine, Bucheon, Republic of Korea.
Choi, S-Y - Leukemia Research Institute, College of Medicine, The Catholic University of Korea, Seoul.
Kim, S-H - Leukemia Research Institute, College of Medicine, The Catholic University of Korea, Seoul.
Kim, D-W - Department of Hematology, Catholic BMT Center Leukemia Research Institute, College of Medicine, The Catholic University of Korea, Seoul.
Lee, S - Department of Hematology, Catholic BMT Center Leukemia Research Institute, College of Medicine, The Catholic University of Korea, Seoul leeseok@catholic.ac.kr.
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. PATIENTS AND
METHODS: 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.
RESULTS: 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. CONCLUSION: This dasatinib-based protocol was effective for achieving a good quality molecular response and durable DFS in adults with Ph-positive ALL. TRIAL REGISTRATION: clinicaltrials.gov, NCT01004497. CI - ??The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.
keyword
Philadelphia chromosome; acute lymphoblastic leukemia; allogeneic stem cell transplantation; dasatinib; minimal residual disease
¸µÅ©