Dasatinib and low-intensity chemotherapy in elderly patients with Philadelphia chromosome–positive ALL
In: Blood, Jg. 128 (2016-08-11), Heft 6, S. 774-782
serialPeriodical
Zugriff:
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-ABL1T315I 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-ABL1T315I from diagnosis identified patients with at high risk of early relapse and may help to personalize therapy.
Titel: |
Dasatinib and low-intensity chemotherapy in elderly patients with Philadelphia chromosome–positive ALL
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Autor/in / Beteiligte Person: | Rousselot, Philippe ; Coudé, Marie Magdelaine ; Gokbuget, Nicola ; Gambacorti Passerini, Carlo ; Hayette, Sandrine ; Cayuela, Jean-Michel ; Huguet, Françoise ; Leguay, Thibaut ; Chevallier, Patrice ; Salanoubat, Celia ; Bonmati, Caroline ; Alexis, Magda ; Hunault, Mathilde ; Glaisner, Sylvie ; Agape, Philippe ; Berthou, Christian ; Jourdan, Eric ; Fernandes, José ; Sutton, Laurent ; Banos, Anne ; Reman, Oumedaly ; Lioure, Bruno ; Thomas, Xavier ; Ifrah, Norbert ; Lafage-Pochitaloff, Marina ; Bornand, Anne ; Morisset, Laure ; Robin, Valérie ; Pfeifer, Heike ; Delannoy, Andre ; Ribera, Josep ; Bassan, Renato ; Delord, Marc ; Hoelzer, Dieter ; Dombret, Herve ; Ottmann, Oliver G. |
Zeitschrift: | Blood, Jg. 128 (2016-08-11), Heft 6, S. 774-782 |
Veröffentlichung: | 2016 |
Medientyp: | serialPeriodical |
ISSN: | 0006-4971 (print) ; 1528-0020 (print) |
DOI: | 10.1182/blood-2016-02-700153 |
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