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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
 J.-H. Yoon  ;  H-Y. Yhim  ;  J-Y. Kwak  ;  J.-S. Ahn  ;  D.-H. Yang  ;  J.-J. Lee  ;  S.-J. Kim  ;  J.-S. Kim  ;  S. J. Park  ;  C.W. Choi  ;  H.-S. Eom  ;  S.-K. Park  ;  S.-Y. Choi  ;  S.-H. Kim  ;  D.-W. Kim  ;  S. Lee 
Citation
 ANNALS OF ONCOLOGY, Vol.27(6) : 1081-1088, 2016 
Journal Title
 ANNALS OF ONCOLOGY 
ISSN
 0923-7534 
Issue Date
2016
MeSH
Adult ; Aged ; Dasatinib/administration & dosage* ; Disease-Free Survival ; Female ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/epidemiology ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/pathology ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/therapy* ; Male ; Middle Aged ; Neoplasm, Residual/epidemiology ; Neoplasm, Residual/pathology* ; Philadelphia Chromosome ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/epidemiology ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy* ; Remission Induction ; Stem Cell Transplantation ; Transplantation, Homologous ; Treatment Outcome
Keywords
Philadelphia chromosome ; acute lymphoblastic leukemia ; allogeneic stem cell transplantation ; dasatinib ; minimal residual disease
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.
Full Text
https://academic.oup.com/annonc/article-lookup/doi/10.1093/annonc/mdw123
DOI
10.1093/annonc/mdw123
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Soo Jeong(김수정) ORCID logo https://orcid.org/0000-0001-8859-3573
Kim, Jin Seok(김진석) ORCID logo https://orcid.org/0000-0001-8986-8436
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/152802
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