| Literature DB >> 27121472 |
Philippe Rousselot1, Marie Magdelaine Coudé2, Nicola Gokbuget3, Carlo Gambacorti Passerini4, Sandrine Hayette5, Jean-Michel Cayuela2, Françoise Huguet6, Thibaut Leguay7, Patrice Chevallier8, Celia Salanoubat9, Caroline Bonmati10, Magda Alexis11, Mathilde Hunault12, Sylvie Glaisner13, Philippe Agape14, Christian Berthou15, Eric Jourdan16, José Fernandes17, Laurent Sutton18, Anne Banos19, Oumedaly Reman20, Bruno Lioure21, Xavier Thomas5, Norbert Ifrah12, Marina Lafage-Pochitaloff22, Anne Bornand23, Laure Morisset24, Valérie Robin25, Heike Pfeifer26, Andre Delannoy27, Josep Ribera28, Renato Bassan29, Marc Delord30, Dieter Hoelzer31, Herve Dombret32, Oliver G Ottmann33.
Abstract
Prognosis of Philadelphia-positive (Ph(+)) acute lymphoblastic leukemia (ALL) in the elderly has improved during the imatinib era. We investigated dasatinib, another potent tyrosine kinase inhibitor, in combination with low-intensity chemotherapy. Patients older than age 55 years were included in the European Working Group on Adult ALL (EWALL) study number 01 for Ph(+) ALL (EWALL-PH-01 international study) and were treated with dasatinib 140 mg/day (100 mg/day over 70 years) with intrathecal chemotherapy, vincristine, and dexamethasone during induction. Patients in complete remission continued consolidation with dasatinib, sequentially with cytarabine, asparaginase, and methotrexate for 6 months. Maintenance therapy was dasatinib and vincristine/dexamethasone reinductions for 18 months followed by dasatinib until relapse or death. Seventy-one patients with a median age of 69 years were enrolled; 77% had a high comorbidity score. Complete remission rate was 96% and 65% of patients achieved a 3-log reduction in BCR-ABL1 transcript levels during consolidation. Only 7 patients underwent allogeneic hematopoietic stem cell transplantation. At 5 years, overall survival was 36% and up to 45% taking into account deaths unrelated to disease or treatment as competitors. Thirty-six patients relapsed, 24 were tested for mutation by Sanger sequencing, and 75% were T315I-positive. BCR-ABL1(T315I) was tested by allele-specific oligonucleotide reverse transcription-quantitative polymerase chain reaction in 43 patients and detection was associated with short-term relapses. Ten patients (23%) were positive before any therapy and 8 relapsed, all with this mutation. In conclusion, dasatinib combined with low-intensity chemotherapy was well-tolerated and gave long-term survival in 36% of elderly patients with Ph(+) ALL. Monitoring of BCR-ABL1(T315I) from diagnosis identified patients with at high risk of early relapse and may help to personalize therapy.Entities:
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Year: 2016 PMID： 27121472 PMCID： PMC5085255 DOI： 10.1182/blood-2016-02-700153
Source DB: PubMed Journal: Blood ISSN： 0006-4971 Impact factor: 22.113