Minimal residual disease monitoring cannot fully replace bone marrow morphology in assessing disease status in pediatric acute lymphoblastic leukemia

Abstract

Minimal residual disease monitoring cannot fully replace bone marrow morphology in assessing disease status in pediatric acute lymphoblastic leukemia. APMIS 2020; 128: 414-419.Minimal residual disease (MRD) monitoring has a strong prognostic value in childhood lymphoblastic leukemia (ALL) and is currently utilized in all major pediatric ALL protocols. MRD monitoring is done by multiparameter flow cytometry, IG/TCR quantitative PCR or reverse transcriptase quantitative PCR of leukemic fusion transcripts providing a reliable measurement of treatment response. However, occasionally bone marrow (BM) aspirates may not yield representative material or be misinterpreted due to treatment-induced changes in MRD marker profile, undetected subclones at diagnosis, contamination with peripheral blood or cell adhesion and stroma cell interactions posing a risk for underestimating MRD levels and misclassifying resistant disease that may be detected by traditional BM morphology methods, immunohistochemistry, karyotyping and FISH. We present four cases with high MRD levels where MRD monitoring failed to provide the correct stratification information. Through these cases, we discuss the continued need to consider all available information including BM smears, touch imprints and trephine biopsy preparations not only at diagnosis but throughout remission monitoring in pediatric ALL.

Post-chemotherapy Changes in Bone Marrow in Acute Leukemia With Emphasis on Detection of Residual Disease by Immunohistochemistry

“…Despite the current use of flow cytometry and quantitative PCR test for MRD assessment, recently, there were very few studies highlighting the need for post-induction bone marrow examination to monitor residual disease status in addition to the present study. Rathe et al reported the importance of a complete bone marrow examination (aspirate, imprint, and trephine biopsy) along with IHC in post-induction remission assessment of ALL cases, in addition to the flow cytometry and quantitative PCR, which failed to detect MRD [ 14 ]. Similarly, another study (sample size=246) highlighted the role of bone marrow examination (especially bone marrow biopsy) for the morphologic assessment of residual disease in AML [ 15 ].…”

Comparison of Multiparameter Flow Cytometry and ClonoSEQ Studies for Precursor B-Lymphoblastic Leukemia Minimal Residual Disease Detection on Bone Marrow Samples

“…It is also true that MRD value may very low, e.g., less than 1% by MFC and molecular methods, while there is resistant disease with more than 20% B-lymphoblasts, as reported by Rathe, et al [16]. Despite MRD monitoring by MFC and NGS cannot fully replace bone marrow morphology in assessing disease status in acute leukemias, as recommended in a series of case report by Rathe [16], the finding in our study and others indicate the limitation of morphologic evaluation on B-ALL residual disease evaluation. Clusters of immature B-cells may not necessary indicate residual leukemic cells and could represent regenerate B-cell precursors.…”