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Excellent outcome after consolidation with autologous transplantation in patients with core binding factor acute myeloid leukemia

Bone Marrow Transplantation volume 55, pages 1690–1693 (2020)Cite this article

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Core binding factor (CBF) leukemias represented by t(8;21)(q22;q22) with the RUNX1-RUNX1T1 rearrangement and inv(16)(p13q22)/t(16;16)(p13;q22) with CBFB-MYH11 are identified in 10–15% of all patients with acute myeloid leukemia (AML) [1]. The respective rearrangements disrupt genes encoding for subunits of CBF, a transcription factor essential during regulation of hematopoiesis. Although prognosis of patients with CBF-AML in general is favorable [2], significant clinical heterogeneity is observed, and relapse incidence is around 40% even in patients undergoing intensive induction and consolidation treatment. Outcomes tend to be slightly less favorable in patients with the t(8;21)/RUNX1-RUNX1T1 as compared with the inv(16)/CBFB-MYH11. Mutations in genes activating tyrosine kinase signaling including KIT, N/KRAS, and FLT3 were detected with high frequencies in t(8;21)/RUNX1-RUNX1T1-positive AML, while being rare in inv(16)/CBFB-MYH11. High mutant KIT allele ratios defined a group of t(8;21)/RUNX1-RUNX1T1 patients with comparably poor prognosis, whereas high NRAS and KRAS mutant allele ratios lack KIT or FLT3 mutations and harbor favorable outcomes [3]. The expression of KIT was found to be higher in CBF-AML (even in KIT wild-type) as compared with other AML subgroups [4].

Patients with CBF-AML achieving a complete remission (CR) following induction chemotherapy are not considered candidates for allogeneic stem cell transplantation in first remission [5], but commonly receive chemotherapy consolidation with high-dose cytarabine. Addition of the multikinase inhibitor dasatinib to induction, consolidation, and maintenance therapy is being explored in CBF-AML [4]. Allogeneic stem cell transplantation is limited to patients with CBF-AML with molecular or clinical relapses following chemotherapy consolidation [6]. However, few data exist on the role of high-dose chemotherapy followed by autologous transplantation (ASCT) for consolidation of first-line treatment in CBF-AML.

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Funding

This work was supported by a grant of the EMPIRIS foundation to TP.

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Author notes

  1. These authors contributed equally: Martin Sula, Ulrike Bacher

Authors and Affiliations

  1. Department of Medical Oncology, University Hospital and University of Bern, Bern, Switzerland

    Martin Sula, Urban Novak & Thomas Pabst

  2. Department of Hematology, University Hospital and University of Bern, Bern, Switzerland

    Ulrike Bacher, Elisabeth Oppliger Leibundgut & Behrouz Mansouri Taleghani

  3. Center of Laboratory Medicine, University Hospital and University of Bern, Bern, Switzerland

    Ulrike Bacher

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  1. Martin Sula
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Contributions

Design of study and data analysis: TP and MS; contribution of vital and laboratory material: UN, UB, and BMT; writing of manuscript: MS, TP, and UB; critical review and final approval of manuscript: all authors.

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Correspondence to Thomas Pabst.

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Sula, M., Bacher, U., Oppliger Leibundgut, E. et al. Excellent outcome after consolidation with autologous transplantation in patients with core binding factor acute myeloid leukemia. Bone Marrow Transplant 55, 1690–1693 (2020). https://doi.org/10.1038/s41409-019-0762-3

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