Significance of minimal residual disease monitoring by real-time quantitative polymerase chain reaction in core binding factor acute myeloid leukemia for transplantation outcomes

Cancer. 2020 May 15;126(10):2183-2192. doi: 10.1002/cncr.32769. Epub 2020 Feb 26.

Abstract

Background: Despite the well-defined role of minimal residual disease (MRD) monitoring by real-time quantitative polymerase chain reaction (RT-PCR) for RUNX1/RUNX1T1 and CBFB-MYH11 transcripts in core binding factor (CBF) acute myeloid leukemia (AML) after intensive chemotherapy, there has been a paucity of data assessing the utility of MRD monitoring at and after allogeneic hematopoietic stem cell transplantation (HSCT).

Methods: Patients with CBF AML who underwent HSCT in complete remission (first or second) from January 2007 through December 2018 were included in this analysis.

Results: MRD by polymerase chain reaction at HSCT was assessed in 50 of 76 patients, and 44 (88%) had evidence of MRD (MRDpos). MRDpos patients had 3-year overall survival (OS) and leukemia-free survival (LFS) rates of 69.3% and 66.3%, respectively. Six MRD-negative patients had 3-year OS and LFS rates of 100% and 100%, respectively. Thirty-five of the 70 evaluable patients (50%) had a day +100 MRD assessment by RT-PCR, and 14 (40%) were MRDpos. The presence of MRD by RT-PCR on day +100 was not associated with lower estimates of LFS (75% vs 82.2%; P = .3) but was associated with a higher relapse incidence, although the difference did not reach statistical significance (27.6% vs 9.7%; P = .2).

Conclusions: Durable complete remissions can be achieved in patients with CBF AML with HSCT even if they are MRDpos by RT-PCR at HSCT. The clinical impact of frequent MRD monitoring for identifying a group at high risk for early relapse and then for determining the best time point for therapeutic interventions to prevent impending relapse warrants investigation in prospectively designed clinical trials.

Keywords: acute myeloid leukemia; allogeneic stem cell transplantation; core binding factor leukemia; measurable residual disease; real-time quantitative polymerase chain reaction (RT-PCR).

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Core Binding Factor Alpha 2 Subunit / genetics
  • Core Binding Factor beta Subunit / genetics
  • Core Binding Factors / genetics*
  • Female
  • Hematopoietic Stem Cell Transplantation
  • Humans
  • Leukemia, Myeloid, Acute / diagnosis*
  • Leukemia, Myeloid, Acute / genetics
  • Leukemia, Myeloid, Acute / therapy
  • Male
  • Middle Aged
  • Myosin Heavy Chains / genetics
  • Neoplasm, Residual / diagnosis*
  • Neoplasm, Residual / genetics
  • Neoplasm, Residual / therapy
  • Oncogene Proteins, Fusion / genetics
  • Prognosis
  • RUNX1 Translocation Partner 1 Protein / genetics
  • Real-Time Polymerase Chain Reaction / methods*
  • Transplantation, Homologous

Substances

  • CBFB protein, human
  • Core Binding Factor Alpha 2 Subunit
  • Core Binding Factor beta Subunit
  • Core Binding Factors
  • MYH11 protein, human
  • Oncogene Proteins, Fusion
  • RUNX1 Translocation Partner 1 Protein
  • RUNX1 protein, human
  • RUNX1T1 protein, human
  • Myosin Heavy Chains