How I Diagnose Minimal/Measurable Residual Disease in B Lymphoblastic Leukemia/Lymphoma by Flow Cytometry

Assessment for minimal/measurable residual disease (MRD) is a powerful prognostic factor in B lymphoblastic leukemia/lymphoma (B-LL/L) that is quickly becoming standard of care in assessing patients with B-LL/L posttherapy. MRD can be assessed using methodologies including flow cytometry and molecular genetics, with the former being rapid, relatively inexpensive, and widely applicable in many hematopathology/flow cytometry laboratories.

This article presents an approach to MRD detection in B-LL/L by flow cytometry through case presentations with illustration of several potential pitfalls. We review normal maturation patterns, antigens used for assessment, flow panels that can be utilized, considerations to be made during therapy, and clinical impact. The benefits and drawbacks when using the "different from normal" and "leukemia associated phenotype" approaches are considered.

Evaluation for MRD in B-LL/L by flow cytometry relies on a knowledge of normal immunophenotypic patterns associated with B-cell maturation in states of rest and marrow regeneration so that one can identify patterns of antigen expression that differentiate abnormal, leukemic populations from regenerating hematogones or B-cell precursors. The nature of therapy can affect normal patterns, a phenomenon especially important to take into consideration given the increased use of targeted therapies in the treatment of B-LL/L.

Flow cytometry is widely available in many laboratories and is a cost-effective way to evaluate for B-LL/L MRD. However, panel validation and interpreter education are crucial for accurate assessment.