Biomarkers Consortium - Minimal Residual Disease (MRD) Detection in Adult Acute Lymphoblastic Leukemia (ALL)

This project completed in December 2019.

Leukemias are life-threatening, but treatable, cancers of the blood or bone marrow resulting in abnormally high numbers of immature white blood cells. Minimal residual disease (MRD) is the number of leukemic cells detected in the blood or bone marrow of a patient in a state of remission after treatment is completed. MRD has been investigated extensively in pediatric acute lymphoblastic leukemia (ALL), and its detection is associated with subsequent relapse, event-free or relapse-free survival (EFS or RFS, respectively). However, data concerning the association of MRD to outcomes in adult ALL have not been as well investigated. The goal of the Minimal Residual Disease Detection in Adult Acute Lymphoblastic Leukemia project is to establish MRD as an indicator of clinical outcomes in adult ALL. An additional goal of the project is to standardize methodologies used for laboratory analyses of MRD. The project, supported through the Biomarkers Consortium and conducted and funded by a number of collaborating institutions as members of the project team, launched in late 2014.

A trial level meta-analysis from published data conducted by the MRD in All team suggests high correlation between EFS and MRD and that MRD has potential to be a surrogate endpoint for ALL. However, a more detailed analysis of the data will need to be conducted to prove MRD’s surrogacy in ALL. The FDA will lead a patient level analysis as a next step in this qualification process, and this work is currently ongoing. In addition, the team continues to work on developing better flow cytometry assays for the detection of MRD in ALL and hopes to eventually have these kits approved by the FDA.


  • Evaluate existing data to determine the utility of MRD for predicting event-free survival (EFS) in pediatric and adult ALL.
  • Standardize MRD testing in Intergroup labs and export standardization to the community.

Results & Accomplishments

Guidance Documents

Meta-analysis will follow PRISMA guidelines

Scientific Publications

A QA program for MRD testing demonstrates that systematic education can reduce discordance among experienced interpreters. Keeney M, Wood BL, Hedley BD, DiGiuseppe JA, Stetler-Stevenson M, Paietta E, Lozanski G, Seegmiller AC, Greig BW, Shaver AC, Mukundan L, Higley HR, Sigman CC, Kelloff G, Jessup JM, Borowitz MJ. Cytometry B Clin Cytom. 2017 May 5. doi: 10.1002/cyto.b.21528. [Epub ahead of print] PMID: 28475275

Association of Minimal Residual Disease With Clinical Outcome in Pediatric and Adult Acute Lymphoblastic Leukemia: A Meta-analysis. Berry DA, Zhou S, Higley H, Mukundan L, Fu S, Reaman GH, Wood BL, Kelloff GJ, Jessup JM, Radich JP. JAMA Oncol. 2017 May 11:e170580. doi: 10.1001/jamaoncol.2017.0580. [Epub ahead of print] PMID: 28494052


Public-Sector Partners:
National Cancer Institute (NCI)
U.S. Food and Drug Administration (FDA)

Private-Sector Partners:
AbbVie Inc.*
Amgen, Inc.*
BD Biosciences, Becton Dickinson and Company*
Beckman Coulter, Beckman Coulter Life Sciences*
Genentech, a member of the Roche Group*
Pfizer Inc*

Academic Partners:
Hartford Health Hospital
Johns Hopkins University
Lawson Health Research Institute
MD Anderson Cancer Center
Montefiore Medical Center
Ohio State University
University of Washington
Vanderbilt University

*Provided financial or in-kind support for this program.

FNIH Contact

Stacey J. Adam, Ph.D. Director, Cancer;