Evaluation of MRD Testing in B-ALL

The standard-of-care for monitoring treatment response in B-lymphoblastic leukemia (B-ALL) is measurable residual disease (MRD) testing. Several testing methodologies, including immunophenotypic (flow cytometric) and molecular (polymerase chain reaction and next-generation sequencing) assays, are currently utilized. Moreover, optimal assays, treatment time points, specimen types, and specimen quality considerations are not established. The goal of this guideline is to establish evidence-based standards and expert recommendations on MRD testing methodologies and specimen considerations for pediatric and adult B-ALL. The guideline draft statements are now available for public comment and feedback; participation is encouraged by October 29, 2025.

The primary goal of this guideline is to address clinical evaluation of MRD in B-ALL. The evidence-based recommendations will focus on optimal MRD testing methods.

1a. In patients with Philadelphia chromosome negative (Ph-) B-ALL, which method (flow cytometry or NGS) is best for evaluating MRD status at post-induction, post-consolidation, pretransplant, and posttransplant treatment timepoints?

1b. In patients with Philadelphia chromosome positive (Ph+) B-ALL, which method (PCR, flow cytometry, or NGS) is best for evaluating MRD status at post-induction, post-consolidation, pretransplant, and posttransplant treatment timepoints?

2. In patients with B-ALL, do peripheral blood specimens have concordance with bone marrow aspirates for detecting MRD?

3. For bone marrow aspirates from B-ALL patients, what are the optimum and minimum cellularity requirements for accurate assessment of MRD?

• Guideline status: Open Comment Period
• Collaborators: Association for Molecular Pathology (AMP) and International Clinical Cytometry Society (ICCS)

All stakeholders—including pathologists, oncologists, hospital or laboratory managers, and patient advocacy group representatives—are encouraged to participate and provide feedback on the draft statements by October 29, 2025.

Review the following resources to provide your feedback:
•    Data extraction references
•    Draft statements and GRADE glossary
•    Expert panel disclosures of interest report 

PROSPERO Listing

The information, data, and draft recommendations provided by the College of American Pathologists are presented for informational and public feedback purposes only. The draft recommendations and supporting documents will be removed on November 5, 2025. The draft recommendations along with the public comments received and completed evidence review will be reassessed by the expert panel in order to formulate the final recommendations.

These draft materials should not be stored, adapted, or redistributed in any manner.

Please note: comments are not posted automatically. All comments will be posted on a weekly basis beginning October 15, 2025.