title: Minimal residual disease-based effect and long-term outcome of first-line dasatinib combined with chemotherapy for adult Philadelphia chromosome-positive acute lymphoblastic leukemia.
abstract: 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.
authors.affiliation: Department of Hematology, Catholic BMT Center; Leukemia Research Institute, College of Medicine, The Catholic University of Korea, Seoul.
authors.forename: J-H
authors.initials: JH
authors.lastname: Yoon
authors.affiliation: Division of Hematology-Oncology, Department of Internal Medicine, Chonbuk National University Medical School, Jeonju.
authors.forename: H-Y
authors.initials: HY
authors.lastname: Yhim
authors.affiliation: Division of Hematology-Oncology, Department of Internal Medicine, Chonbuk National University Medical School, Jeonju.
authors.forename: J-Y
authors.initials: JY
authors.lastname: Kwak
authors.affiliation: Department of Hematology-Oncology, Chonnam National University Hwasun Hospital, Jeollanamdo.
authors.forename: J-S
authors.initials: JS
authors.lastname: Ahn
authors.affiliation: Department of Hematology-Oncology, Chonnam National University Hwasun Hospital, Jeollanamdo.
authors.forename: D-H
authors.initials: DH
authors.lastname: Yang
authors.affiliation: Department of Hematology-Oncology, Chonnam National University Hwasun Hospital, Jeollanamdo.
authors.forename: J-J
authors.initials: JJ
authors.lastname: Lee
authors.affiliation: Division of Hematology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul.
authors.forename: S-J
authors.initials: SJ
authors.lastname: Kim
authors.affiliation: Division of Hematology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul.
authors.forename: J-S
authors.initials: JS
authors.lastname: Kim
authors.affiliation: Division of Hematology-Oncology, Department of Internal Medicine, Korea University School of Medicine, Seoul.
authors.forename: S J
authors.initials: SJ
authors.lastname: Park
authors.affiliation: Division of Hematology-Oncology, Department of Internal Medicine, Korea University School of Medicine, Seoul.
authors.forename: C W
authors.initials: CW
authors.lastname: Choi
authors.affiliation: Hematologic Oncology Clinic, Center for Specific Organs Center, National Cancer Center, Goyang.
authors.forename: H-S
authors.initials: HS
authors.lastname: Eom
authors.affiliation: Division of Hematology-Oncology, Department of Internal Medicine, Soonchunhyang University School of Medicine, Bucheon, Republic of Korea.
authors.forename: S-K
authors.initials: SK
authors.lastname: Park
authors.affiliation: Leukemia Research Institute, College of Medicine, The Catholic University of Korea, Seoul.
authors.forename: S-Y
authors.initials: SY
authors.lastname: Choi
authors.affiliation: Leukemia Research Institute, College of Medicine, The Catholic University of Korea, Seoul.
authors.forename: S-H
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Department of Hematology, Catholic BMT Center; Leukemia Research Institute, College of Medicine, The Catholic University of Korea, Seoul.
authors.forename: D-W
authors.initials: DW
authors.lastname: Kim
authors.affiliation: Department of Hematology, Catholic BMT Center; Leukemia Research Institute, College of Medicine, The Catholic University of Korea, Seoul. Electronic address: leeseok@catholic.ac.kr.
authors.forename: S
authors.initials: S
authors.lastname: Lee
mesh_terms: D000328:Adult; D000368:Aged; D000069439:Dasatinib / Q000008:administration & dosage*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000453:epidemiology / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D018365:Neoplasm, Residual / Q000453:epidemiology / Q000473:pathology*; D010677:Philadelphia Chromosome; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000453:epidemiology / Q000473:pathology / Q000628:therapy*; D012074:Remission Induction; D033581:Stem Cell Transplantation; D014184:Transplantation, Homologous; D016896:Treatment Outcome
chemical_list: D000069439:Dasatinib
keywords: Philadelphia chromosome; acute lymphoblastic leukemia; allogeneic stem cell transplantation; dasatinib; minimal residual disease