Complex karyotype, older age, and reduced first-line dose intensity determine poor survival in core binding factor acute myeloid leukemia patients with long-term follow-up

Mosna, Federico ; Papayannidis, Cristina ; Martinelli, Giovanni ; Bonalumi, Angela ; Tecchio, Cristina ; Candoni, Anna ; Capelli, Debora ; Piccin, Andrea ; Forghieri, Fabio ; Bigazzi, Catia ; Visani, Giuseppe ; Zambello, Renato ; Zanatta, Lucia ; Volpato, Francesca ; Paolini, Stefania ; Testoni, Nicoletta ; Gherlinzoni, Filippo ; Gottardi, Michele (2015) Complex karyotype, older age, and reduced first-line dose intensity determine poor survival in core binding factor acute myeloid leukemia patients with long-term follow-up. American Journal Of Hematology, 90 (6). pp. 471-575.
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Abstract

Approximately 40% of patients affected by core binding factor (CBF) acute myeloid leukemia (AML) ultimately die from the disease. Few prognostic markers have been identified. In this study we reviewed 192 patients with core binding factor acute myeloid leukemia (AML), treated with curative intent (age, 15-79 years) in 11 Italian institutions. Overall, 10-year overall survival (OS), disease-free survival (DFS), and event-free survival were 63.9%, 54.8%, and 49.9%, respectively; patients with the t(8;21) and inv(16) chromosomal rearrangements exhibited significant differences at diagnosis. Despite similarly high complete remission (CR) rate, patients with inv(16) experienced superior DFS and a high chance of achieving a second CR, often leading to prolonged OS also after relapse. We found that a complex karyotype (ie, ≥4 cytogenetic anomalies) affected survival; the KIT D816 mutation predicted worse prognosis only in patients with the t(8;21) rearrangement, whereas FLT3 mutations had no prognostic impact. We then observed increasingly better survival with more intense first-line therapy, in some high-risk patients including autologous or allogeneic hematopoietic stem cell transplantation. In multivariate analysis, age, severe thrombocytopenia, elevated lactate dehydrogenase levels, and failure to achieve CR after induction independently predicted longer OS, whereas complex karyotype predicted shorter OS only in univariate analysis. The achievement of minimal residual disease negativity predicted better OS and DFS. Long-term survival was also observed in a minority of elderly patients who received intensive consolidation treatment. All considered, we identified also among CBF AML patients a subgroup with poorer prognosis who might benefit from more intense first-line treatment.

Abstract
Document type
Article
Creators
CreatorsAffiliationORCID
Mosna, Federico
Papayannidis, Cristina
Martinelli, Giovanni
Bonalumi, Angela
Tecchio, Cristina
Candoni, Anna
Capelli, Debora
Piccin, Andrea
Forghieri, Fabio
Bigazzi, Catia
Visani, Giuseppe
Zambello, Renato
Zanatta, Lucia
Volpato, Francesca
Paolini, Stefania
Testoni, Nicoletta
Gherlinzoni, Filippo
Gottardi, Michele
Keywords
Core Binding Factor; AML; chemotherapy; t(8;21); inv(16)
Subjects
DOI
Deposit date
07 Jan 2016 09:22
Last modified
01 Jun 2016 21:00
Project name
NGS-PTL - Next Generation Sequencing platform for targeted Personalized Therapy of Leukemia
Funding program
EC - FP7
URI

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