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Genomic CDKN2A/2B deletions in adult Ph+ ALL are adverse despite allogeneic stem cell transplantation

Pfeifer, Heike, Raum, Katharina, Markovic, Sandra, Nowak, Verena, Fey, Stephanie, Obländer, Julia, Pressler, Jovita, Böhm, Verena, Brüggemann, Monika, Wunderle, Lydia, Hüttmann, Andreas, Wäsch, Ralph, Beck, Joachim, Stelljes, Matthias, Viardot, Andreas, Lang, Fabian, Hoelzer, Dieter, Hofmann, Wolf-Karsten, Serve, Hubert, Weiss, Christel, Goekbuget, Nicola, Ottmann, Oliver G. and Nowak, Daniel 2018. Genomic CDKN2A/2B deletions in adult Ph+ ALL are adverse despite allogeneic stem cell transplantation. Blood 131 , pp. 1464-1475. 10.1182/blood-2017-07-796862

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Abstract

We investigated the role of copy number alterations to refine risk stratification in adult Philadelphia chromosome positive (Ph)+ ALL treated with tyrosine kinase inhibitors (TKI) and allogeneic stem cell transplantation (aSCT). 97 Ph+ ALL patients (median age 41 years, range 18-64 years) within the prospective multicenter GMALL studies 06/99 (n=8) and 07/2003 (n=89) were analysed. All patients received TKI and aSCT in first complete remission (CR1). Copy number analysis was performed with SNP arrays and validated by multiplex ligation-dependent probe amplification (MLPA). The frequencies of recurrently deleted genes were: IKZF1, 76%, CDKN2A/2B, 45%, PAX5, 43%, BTG1, 18%, EBF1, 13%, ETV6, 5%, RB, 14%. In univariate analyses, the presence of CDKN2A/2B deletions had a negative impact on all endpoints: overall survival (p=0.023), disease free survival (p=0.012) and remission duration (p=0.036). The negative predictive value of CDKN2A/2B deletions was retained in multivariable analysis along with other factors such as timing of TKI therapy, intensity of conditioning, achieving remission after induction phase I and BTG1 deletions. We therefore conclude that acquired genomic CDKN2A/2B deletions identify a subgroup of Ph+ ALL patients, who have an inferior prognosis despite aSCT in CR1. Their poor outcome was attributable primarily to a high relapse rate after aSCT.

Item Type: Article
Date Type: Published Online
Status: Published
Schools: Medicine
Publisher: American Society of Hematology
ISSN: 0006-4971
Date of First Compliant Deposit: 29 January 2018
Date of Acceptance: 1 January 2018
Last Modified: 18 Jan 2019 02:30
URI: http://orca.cf.ac.uk/id/eprint/108549

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