Prognosis of Philadelphia-positive (Ph1) acutelymphoblastic 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 18months followed by dasatinib until relapse or death. Seventy-one patients with amedian age of 69 years were enrolled; 77% had a high comorbidity score.Complete remission ratewas 96% and 65% of patients achieved a3-logreduction inBCR-ABL1transcript levelsduringconsolidation.Only7patientsunderwent allogeneic hematopoietic stemcell transplantation. At 5 years, overall survivalwas 36% and up to 45% taking into account deaths unrelated to disease or treatment as competitors. Thirty-six patients relapsed, 24were tested formutation bySanger sequencing, and 75%were T315I-positive.BCR-ABL1T315Iwastested 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 BCRABL1T315I from diagnosis identified patientswith at high risk of early relapse and may help to personalize therapy.

Rousselot, P., Coudé, M., Gokbuget, N., Gambacorti Passerini, C., Hayette, S., Cayuela, J., et al. (2016). Dasatinib and low-intensity chemotherapy in elderly patients with Philadelphia chromosome-positive ALL. BLOOD, 128(6), 774-782 [10.1182/blood-2016-02-700153].

Dasatinib and low-intensity chemotherapy in elderly patients with Philadelphia chromosome-positive ALL

Gambacorti Passerini, C;
2016

Abstract

Prognosis of Philadelphia-positive (Ph1) acutelymphoblastic 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 18months followed by dasatinib until relapse or death. Seventy-one patients with amedian age of 69 years were enrolled; 77% had a high comorbidity score.Complete remission ratewas 96% and 65% of patients achieved a3-logreduction inBCR-ABL1transcript levelsduringconsolidation.Only7patientsunderwent allogeneic hematopoietic stemcell transplantation. At 5 years, overall survivalwas 36% and up to 45% taking into account deaths unrelated to disease or treatment as competitors. Thirty-six patients relapsed, 24were tested formutation bySanger sequencing, and 75%were T315I-positive.BCR-ABL1T315Iwastested 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 BCRABL1T315I from diagnosis identified patientswith at high risk of early relapse and may help to personalize therapy.
Articolo in rivista - Articolo scientifico
Dasatinib, TKI, Ph+ ALL
English
2016
128
6
774
782
reserved
Rousselot, P., Coudé, M., Gokbuget, N., Gambacorti Passerini, C., Hayette, S., Cayuela, J., et al. (2016). Dasatinib and low-intensity chemotherapy in elderly patients with Philadelphia chromosome-positive ALL. BLOOD, 128(6), 774-782 [10.1182/blood-2016-02-700153].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/115909
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