Oncotarget

Research Papers:

High BAALC copy numbers in peripheral blood prior to allogeneic transplantation predict early relapse in acute myeloid leukemia patients

Madlen Jentzsch, Marius Bill, Juliane Grimm, Julia Schulz, Karoline Goldmann, Stefanie Beinicke, Janine Häntschel, Wolfram Pönisch, Georg-Nikolaus Franke, Vladan Vucinic, Gerhard Behre, Thoralf Lange, Dietger Niederwieser and Sebastian Schwind _

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Oncotarget. 2017; 8:87944-87954. https://doi.org/10.18632/oncotarget.21322

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Abstract

Madlen Jentzsch1, Marius Bill1, Juliane Grimm1, Julia Schulz1, Karoline Goldmann1, Stefanie Beinicke1, Janine Häntschel1, Wolfram Pönisch1, Georg-Nikolaus Franke1, Vladan Vucinic1, Gerhard Behre1, Thoralf Lange1, Dietger Niederwieser1 and Sebastian Schwind1

1Department of Hematology and Oncology, University of Leipzig, Leipzig, Germany

Correspondence to:

Sebastian Schwind, email: [email protected]

Keywords: acute myeloid leukemia, allogeneic stem cell transplantation, residual disease, BAALC, prognosis

Received: July 18, 2017     Accepted: August 17, 2017     Published: September 27, 2017

ABSTRACT

High BAALC expression levels at acute myeloid leukemia diagnosis have been linked to adverse outcomes. Recent data indicate that high BAALC expression levels may also be used as marker for residual disease following acute myeloid leukemia treatment. Allogeneic hematopoietic stem cell transplantation (HSCT) offers a curative treatment for acute myeloid leukemia patients. However, disease recurrence remains a major clinical challenge and identification of high-risk patients prior to HSCT is crucial to improve outcomes. We performed absolute quantification of BAALC copy numbers in peripheral blood prior (median 7 days) to HSCT in complete remission (CR) or CR with incomplete peripheral recovery in 82 acute myeloid leukemia patients using digital droplet PCR (ddPCR) technology. An optimal cut-off of 0.14 BAALC/ABL1 copy numbers was determined and applied to define patients with high or low BAALC/ABL1 copy numbers. High pre-HSCT BAALC/ABL1 copy numbers significantly associated with higher cumulative incidence of relapse and shorter overall survival in univariable and multivariable models. Patients with high pre-HSCT BAALC/ABL1 copy numbers were more likely to experience relapse within 100 days after HSCT. Evaluation of pre-HSCT BAALC/ABL1 copy numbers in peripheral blood by ddPCR represents a feasible and rapid way to identify acute myeloid leukemia patients at high risk of early relapse after HSCT. The prognostic impact was also observed independently of other known clinical, genetic, and molecular prognosticators. In the future, prospective studies should evaluate whether acute myeloid leukemia patients with high pre-HSCT BAALC/ABL1 copy numbers benefit from additional treatment before or early intervention after HSCT.


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