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

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.

Clonal evolution of acute myeloid leukemia revealed by high-throughput single-cell genomics

“…Immunophenotypes of the bone marrow cells from AML patients were assessed using eight-color flow cytometry on FACSCanto II (BD Biosciences) as part of the routine clinical workup 38 . Briefly, BM cells that were stained with monoclonal antibodies were acquired on FACSCanto II instruments (BD Biosciences).…”

The applicability of multiparameter flow cytometry for the detection of minimal residual disease using different‐from‐normal panels to predict relapse in patients with acute myeloid leukemia after allogeneic transplantation

“…The detectable MRD in patients exhibiting morphologic CR predicts an increased risk of leukemia recurrence and worse outcomes. 3,5,7,18,19 However, currently, a uniform approach for the detection of MRD is unavailable because AML is genetically diverse. PCR-based MRD detection of mutant transcripts is the most sensitive approach and has been widely used to monitor MRD in patients with chronic myelogenous leukemia (CML), Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL), acute promyelocytic leukemia (APL), 20 and a small group of AML subtypes (eg, NPM1/RUNX1-RUNX1T1/CBFB-MYH11/PML-RARA-positive samples).…”

“…However, leukemia relapse still accounts for most deaths after transplantation. [1][2][3][4] Based on accumulating evidence, a minimal residual disease (MRD) assessment has crucial prognostic value for patients with AML in morphologic complete remission (CR) after receiving allo-HSCT. [5][6][7][8][9][10][11] However, questions remain unanswered, particularly regarding the optimal method for MRD detection in patients with AML, which encompasses a wide range of myeloid neoplasms with diverse abnormalities.…”

How close are we to incorporating measurable residual disease into clinical practice for acute myeloid leukemia?

“…The impact of post-HSCT MRD status is, however, less clear. 55,59 While patients with persistent or recurrent MRD after HSCT appear to have relatively poor outcomes, one analysis suggests that pre-HSCT MRD status carries relatively more prognostic information than post-HSCT MRD status. 55 In this study, only pre-HSCT MRD was independently associated with long-term outcomes.…”