Allogeneic stem cell transplantation mitigates the adverse prognostic impact of high diagnostic BAALC and MN1 expression
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ORIGINAL ARTICLE
Allogeneic stem cell transplantation mitigates the adverse prognostic impact of high diagnostic BAALC and MN1 expression in AML Madlen Jentzsch 1 & Marius Bill 1 & Juliane Grimm 1 & Dominic Brauer 1 & Donata Backhaus 1 & Karoline Goldmann 1 & Julia Schulz 1 & Dietger Niederwieser 1 & Uwe Platzbecker 1 & Sebastian Schwind 1 Received: 6 July 2020 / Accepted: 24 August 2020 / Published online: 29 August 2020 # The Author(s) 2020
Abstract For most acute myeloid leukemia (AML) patients, an allogeneic hematopoietic stem cell transplantation (HSCT) offers the highest chance of sustained remissions and long-term survival. At diagnosis, high expression of the AML-associated genes BAALC (brain and acute leukemia, cytoplasmic) and MN1 (meningioma-1) were repeatedly linked to inferior outcomes in patients consolidated with chemotherapy while data for patients receiving HSCT remain limited. Using clinically applicable digital droplet PCR assays, we analyzed the diagnostic BAALC/ABL1 and MN1/ABL1 copy numbers in 302 AML patients. High BAALC/ABL1 and MN1/ABL1 copy numbers associated with common adverse prognostic factors at diagnosis. However, while high diagnostic copy numbers of both genes associated with shorter event free survival (EFS) and overall survival (OS) in patients receiving chemotherapy, there was no prognostic impact in patients undergoing HSCT. Our data suggests that the adverse prognostic impact of high BAALC and MN1 expression are mitigated by allogeneic HSCT. But preHSCT BAALC/ ABL1 and MN1/ABL1 assessed in remission prior to HSCT remained prognosticators for EFS and OS independent of the diagnostic expression status. Whether allogeneic HSCT may improve survival for AML patients with high diagnostic BAALC or MN1 expression should be investigated prospectively and may improve informed decisions towards individualized consolidation options in AML. Keywords Acute myeloid leukemia . BAALC . MN1 . Allogeneic stem cell transplantation
Introduction Acute myeloid leukemia (AML) is a highly heterogeneous disease for which reliable risk stratifications are needed to individualize treatment strategies [1]. Today, potential consolidation therapies for AML patients in remission after successful induction therapy include intensive chemotherapy cycles alone or an allogeneic hematopoietic stem cell transplantation (HSCT). Through immunological graft-versus-leukemia (GvL) effects, where the donor’s immunocompetent cells are believed to eradicate residual disease [2, 3], allogeneic HSCT Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00277-020-04235-8) contains supplementary material, which is available to authorized users. * Sebastian Schwind [email protected] 1
Medical Clinic and Policlinic 1, Hematology and Cellular Therapy, Leipzig University Hospital, Liebigstraße 22, Haus 7, 04103 Leipzig, Germany
remains the treatment option with the highest chance of sustained remissions in most AML patients, albeit the associated morbidity and mort
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