Minimal residual disease-based effect and long-term outcome of first-line dasatinib combined with chemotherapy for adult Philadelphia chromosome-positive acute lymphoblastic leukemia.
Ann Oncol
; 27(6): 1081-1088, 2016 06.
Article
em En
| MEDLINE
| ID: mdl-26951627
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 ANDMETHODS:
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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Leucemia Mielogênica Crônica BCR-ABL Positiva
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Neoplasia Residual
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Leucemia-Linfoma Linfoblástico de Células Precursoras
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Dasatinibe
Tipo de estudo:
Guideline
Limite:
Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article