Measurable residual disease by flow cytometry in acute myeloid leukemia is prognostic, independent of genomic profiling
Copyright © 2022 Elsevier Ltd. All rights reserved..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:123 |
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| Enthalten in: |
Leukemia research - 123(2022) vom: 01. Dez., Seite 106971 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Ganzel, Chezi [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 30.11.2022 Date Revised 16.02.2024 published: Print-Electronic ClinicalTrials.gov: NCT00049517 Citation Status MEDLINE |
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| doi: |
10.1016/j.leukres.2022.106971 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM348461771 |
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| 520 | |a 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 | ||
| 650 | 4 | |a Clinical Trial | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Acute myeloid leukemia | |
| 650 | 4 | |a CD25 | |
| 650 | 4 | |a Flow cytometry | |
| 650 | 4 | |a Genomic profiling | |
| 650 | 4 | |a MRD | |
| 650 | 4 | |a Measurable residual disease | |
| 650 | 4 | |a Minimal residual disease | |
| 700 | 1 | |a Sun, Zhuoxin |e verfasserin |4 aut | |
| 700 | 1 | |a Baslan, Timour |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Yanming |e verfasserin |4 aut | |
| 700 | 1 | |a Gönen, Mithat |e verfasserin |4 aut | |
| 700 | 1 | |a Abdel-Wahab, Omar I |e verfasserin |4 aut | |
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| 700 | 1 | |a Lowe, Scott W |e verfasserin |4 aut | |
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| 700 | 1 | |a Ketterling, Rhett |e verfasserin |4 aut | |
| 700 | 1 | |a Luger, Selina M |e verfasserin |4 aut | |
| 700 | 1 | |a Litzow, Mark |e verfasserin |4 aut | |
| 700 | 1 | |a Lazarus, Hillard M |e verfasserin |4 aut | |
| 700 | 1 | |a Rowe, Jacob M |e verfasserin |4 aut | |
| 700 | 1 | |a Tallman, Martin S |e verfasserin |4 aut | |
| 700 | 1 | |a Levine, Ross L |e verfasserin |4 aut | |
| 700 | 1 | |a Paietta, Elisabeth |e verfasserin |4 aut | |
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