Flow Cytometric Detection of Minimal Residual Disease in Acute Lymphoblastic Leukemia

Abstract

Assessment of minimal residual disease (MRD) during the first months of therapy gives information on the timely response to treatment, and proves to be a powerful and independent indicator of treatment outcome in patients with acute lymphoblastic leukemia (ALL). Immunological evaluation by flow cytometry (FCM) is one of the most attractive approaches to this. The present review summarizes the historical development of this approach over the last 20 years, and shows that current methodology is based on the existence of leukemia-associated patterns of derangement in antigen expression with respect to normal differentiation or location of occurrence. Recent clinical studies are summarized which proved that FCM is applicable to more than 90% of patients with ALL and gives prognostic information comparable to polymerase chain-reaction (PCR)-based technology. Ongoing efforts based on parallel application of both technologies are explained which are designed to clarify which approach bears the best cost-relevance ratio in order to be broadly used in the future for risk assessment and tailoring of treatment modalities. Concluding perspectives relate to further technical developments like usage of peripheral blood (PB) instead of bone marrow (BM), absolute quantification, or strategic placement of investigative time-points, which may allow to simplify the MRD approach and thus augment it's economic efficiency.

Drug-induced immunophenotypic modulation in childhood ALL: implications for minimal residual disease detection

“…This is highly relevant, since flow cytometric day 15 BM results can be used for low-risk definition in ALL patients treated according to BFM treatment protocols. 28 More generally, this is further corroborated by our finding of a strong concordance of MRD data obtained in parallel by flow cytometry and PCR technology in the same cohort of patients along all early time points of treatment. However, some differences have been observed, in particular the median levels of MRD detected by PCR resulted higher, whereas qualitative discordances corresponded mostly to PCR-positive/flow cytometry-negative samples collected at later time points in which hematogones may emerge.…”

Bone marrow minimal disseminated disease (MDD) and minimal residual disease (MRD) in childhood T‐cell lymphoblastic lymphoma stage III, detected by flow cytometry (FC) and real‐time quantitative polymerase chain reaction (RQ‐PCR)

“…More accurate methods to define BM microscopic involvement at diagnosis in order to refine current staging and for subsequent evaluation of early response to treatment may improve treatment stratification. Ours is the first study to apply two state-of-the-art methods concurrently in the evaluation of T-LLy, four-color FC, and RQ-PCR, both of which were found to reach a sensitivity of 0.01% blasts in normal BM cells in T-ALL [23,32,34,37,[39][40][41][42][43][44][45][46][47].…”

Differential expression of 9‐O‐acetylated sialoglycoconjugates on leukemic blasts: A potential tool for long‐term monitoring of children with acute lymphoblastic leukemia

“…3,40 -42 As experienced in BIOMED Concerted Action on MRD, using different triple combinations of antibodies (CD10 -CD20 -CD19, TdT-CD10 -CD19, TdT-CD5-CytCD3), sensitivity of 10 -4 in 82% and 10 -5 in 12% of the samples was reported. 42 Detection of MRD with a sensitivity of 0.01-1.13% has been observed using anti-CD58 antibody. 41 Achatinin-H is capable of detecting 0.1-1% leukemic cells by identifying 9-O-AcSG ϩ cells as a measure of MRD (Fig.…”