Early Post-Transplant Minimal Residual Disease Assessment Improves Risk Stratification in Acute Myeloid Leukemia

Biol Blood Marrow Transplant. 2018 Jul;24(7):1514-1520. doi: 10.1016/j.bbmt.2018.02.003. Epub 2018 Feb 12.

Abstract

We studied if the inclusion of early post-stem cell transplantation (SCT) minimal residual disease (MRD) assessments improved prognostication in patients with acute myeloid leukemia (AML). Two hundred sixty-nine AML patients in morphological complete remission (CR) who underwent a first SCT were included if they had evaluable pre-SCT MRD assessment by multiparametric flow cytometry. Post-SCT MRD assessments were performed at days +30, +100, and +180. The primary outcome was 1-year relapse incidence (RI). Of 269 patients in CR, 83 (30.8%) had detectable MRD pre-SCT. Post-SCT, during routine disease assessment time points, 9 of 241 evaluable patients (3.7%) at day +30, 6 of 191 evaluable patients (3.1%) at day +100, and 4 of 133 evaluable patients (3%) at day +180 were MRD positive while in CR. MRD positivity at day +30 predicted the highest risk of relapse at 1 year (group 1, 1-year RI 78%). Among MRD-negative patients at day +30, either adverse risk category by European Leukemia Net (ELN) or intermediate risk who were aged ≥60 years and/or pre-SCT MRD-positive represented the intermediate-risk group (group 2, 1-year RI 29%). The remaining patients represented the low-risk group (group 3, 1-year RI 5%). For patients in CR beyond day +30 post-SCT, detectable MRD at any time point predicted impending relapse within 2 months. Early post-SCT MRD assessment-combined with pre-SCT MRD assessment, ELN risk category, and age-improves risk stratification for relapse in AML patients post-transplant. Studies aimed at preventing impending relapse in this high-risk population are urgently needed.

Keywords: AML; Minimal residual disease; Risk stratification; Stem cell transplantation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Female
  • Hematopoietic Stem Cell Transplantation
  • Humans
  • Leukemia, Myeloid, Acute / pathology
  • Leukemia, Myeloid, Acute / therapy*
  • Male
  • Middle Aged
  • Neoplasm, Residual / pathology
  • Neoplasm, Residual / therapy*
  • Risk Factors
  • Stem Cell Transplantation / adverse effects*
  • Stem Cell Transplantation / methods
  • Young Adult