Page 86 - 2019_06-Haematologica-web

Ferrata Storti Foundation
Haematologica 2019 Volume 104(6):1168-1175
Acute Myeloid Leukemia
Impact of induction regimen and allogeneic hematopoietic cell transplantation
on outcome in younger adults with
acute myeloid leukemia with
a monosomal karyotype
Frédéric Baron,1 Marian Stevens-Kroef,2 Michal Kicinski,3 Giovanna Meloni,4
Petra Muus,2,5 Jean-Pierre Marie,6 Constantijn J.M. Halkes,7 Xavier Thomas,8
9 10 11 12 Radovan Vrhovac, Francesco Albano, François Lefrère Sr., Simona Sica,
4 13 14 2
Marco Mancini, Adriano Venditti, Anne Hagemeijer, Joop H. Jansen, Sergio
Amadori,13 Theo de Witte,2 Roelof Willemze7 and Stefan Suciu3
1Groupe Interdisciplinaire de Génoprotéomique Appliquée (GIGA), Laboratory of Hematology, University of Liege, Belgium; 2Radboud University Medical Center, Nijmegen, the Netherlands; 3EORTC Headquarters, Brussels, Belgium; 4Department of Hematology, Sapienza University, Rome, Italy; 5King’s College Hospital, London, UK; 6Department of Hematology, Saint Antoine Hospital, Paris, France; 7Leiden University Medical Center, the Netherlands; 8CHU Lyon, France; 9University Hospital Center Zagreb, Croatia; 10University of Bari, Italy; 11Necker Hospital, Paris, France; 12Università Cattolica Sacro Cuore, Roma, Italy; 13University Tor Vergata, Roma, Italy and 14University of Leuven, Belgium
ABSTRACT
Monosomal karyotype confers a poor prognosis in patients with acute myeloid leukemia. Here, we determined the impact of the type of remission-induction chemotherapy and the impact of hav- ing a donor in younger acute myeloid leukemia patients with a monosomal karyotype included in two phase III trials. In the first trial patients were ran- domized to receive either daunorubicin, mitoxantrone, or idarubicin in addition to standard-dose cytarabine and etoposide for induction chemotherapy. In the second trial patients were randomized to standard- dose cytarabine or high-dose cytarabine induction, both with daunorubicin and etoposide. In both trials, patients who achieved a complete remission with or without complete hematologic recovery underwent allogeneic hematopoietic stem cell transplantation if they had a donor; otherwise, they underwent autologous transplantation. In comparison to patients with intermediate-risk cytogenetics without a monosomal karyotype (n=1,584) and with adverse cytogenetics without a monosomal karyotype (n=218), patients with a monosomal karyotype (n=188) were more likely not to achieve a complete remission with or without count recovery [odds ratio=2.85, 95% confidence interval (95%, CI): 2.10-3.88] and had shorter overall survival [hazard ratio, (HR)=2.44, 95% CI: 2.08-2.88]. There was no impact of the type of anthracycline or of the dose of cytarabine on out- comes in patients with a monosomal karyotype. Among monosomal karyotype patients who achieved a complete remission with or without count recovery, HLA-identical related donor availability was associated with longer survival from complete remission with or without count recov- ery (HR=0.59, 95% CI: 0.37-0.95). ClinicalTrials.gov identifiers: AML-10: NCT00002549; AML-12: NCT00004128.
Introduction
The prognosis of young adult patients with intermediate/high-risk acute myel- ogenous leukemia (AML) remains unsatisfactory. With current remission induc- tion chemotherapy, 15-40% of such patients fail to achieve a complete remission (CR), and only 30-50% of them remain alive for more than 5 years.1-4 Approximately 55% of AML patients have at least one chromosomal abnormali-
Correspondence:
FRÉDÉRIC BARON
f.baron@ulg.ac.be
Received: August 17, 2018. Accepted: November 29, 2018. Pre-published: December 6, 2018.
doi:10.3324/haematol.2018.204826
Check the online version for the most updated information on this article, online supplements, and information on authorship & disclosures: www.haematologica.org/content/104/6/1168
©2019 Ferrata Storti Foundation
Material published in Haematologica is covered by copyright. All rights are reserved to the Ferrata Storti Foundation. Use of published material is allowed under the following terms and conditions: https://creativecommons.org/licenses/by-nc/4.0/legalcode. Copies of published material are allowed for personal or inter- nal use. Sharing published material for non-commercial pur- poses is subject to the following conditions: https://creativecommons.org/licenses/by-nc/4.0/legalcode, sect. 3. Reproducing and sharing published material for com- mercial purposes is not allowed without permission in writing from the publisher.
1168
haematologica | 2019; 104(6)
ARTICLE