Measurable residual disease by flow cytometry in acute myeloid leukemia is prognostic, independent of genomic profiling

Ganzel, Chezi, Sun, Zhuoxin, Baslan, Timour, Zhang, Yanming, Gönen, Mithat, Abdel-Wahab, Omar I, Racevskis, Janis, Garrett-Bakelman, Francine, Lowe, Scott W, Fernandez, Hugo F, Ketterling, Rhett, Luger, Selina M, Litzow, Mark, Lazarus, Hillard M, Rowe, Jacob M, Tallman, Martin S, Levine, Ross L, Paietta, Elisabeth (December 2022) Measurable residual disease by flow cytometry in acute myeloid leukemia is prognostic, independent of genomic profiling. Leukemia Research, 123. p. 106971. ISSN 0145-2126

DOI: 10.1016/j.leukres.2022.106971


Measurable residual disease (MRD) assessment provides a potent indicator of the efficacy of anti-leukemic therapy. It is unknown, however, whether integrating MRD with molecular profiling better identifies patients at risk of relapse. To investigate the clinical relevance of MRD in relation to a molecular-based prognostic schema, we measured MRD by flow cytometry in 189 AML patients enrolled in ECOG-ACRIN E1900 trial (NCT00049517) in morphologic complete remission (CR) (28.8 % of the original cohort) representing 44.4 % of CR patients. MRD positivity was defined as ≥ 0.1 % of leukemic bone marrow cells. Risk classification was based on standard cytogenetics, fluorescence-in-situ-hybridization, somatic gene analysis, and sparse whole genome sequencing for copy number ascertainment. At 84.6 months median follow-up of patients still alive at the time of analysis (range 47.0-120 months), multivariate analysis demonstrated that MRD status at CR (p = 0.001) and integrated molecular risk (p = 0.0004) independently predicted overall survival (OS). Among risk classes, MRD status significantly affected OS only in the favorable risk group (p = 0.002). Expression of CD25 (α-chain of the interleukin-2 receptor) by leukemic myeloblasts at diagnosis negatively affected OS independent of post-treatment MRD levels. These data suggest that integrating MRD with genetic profiling and pre-treatment CD25 expression may improve prognostication in AML.

Item Type: Paper
Subjects: diseases & disorders > cancer
diseases & disorders
Investigative techniques and equipment
diseases & disorders > neoplasms
diseases & disorders > cancer > cancer types > acute myeloid leukemia
Investigative techniques and equipment > flow cytometry
diseases & disorders > cancer > cancer types > leukemia
diseases & disorders > cancer > prognosis
diseases & disorders > cancer > cancer types
CSHL Authors:
Communities: CSHL labs > Krasnitz lab
CSHL labs > Lowe lab
SWORD Depositor: CSHL Elements
Depositing User: CSHL Elements
Date: December 2022
Date Deposited: 02 Oct 2023 18:43
Last Modified: 11 Jan 2024 20:12
PMCID: PMC9789386
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