Should evaluation for minimal residual disease be routine in acute myeloid leukemia?

Coustan‐Smith, Elaine; Campana, Dario

doi:10.1097/moh.0b013e32835dd90a

Cited by 34 publications

(43 citation statements)

References 64 publications

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“…Therefore, measuring MRD levels at key points during chemotherapy can steer decisions about intensity of subsequent chemotherapy and eligibility for allogeneic hematopoietic stem cell transplantation (1,57). Moreover, MRD is likely to become increasingly used as eligibility and response criteria in clinical trials of new anti-AML agents.…”

Section: Discussionmentioning

confidence: 99%

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Universal monitoring of minimal residual disease in acute myeloid leukemia

et al. 2018

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Section: Discussionmentioning

confidence: 99%

“…Nevertheless, leukemia may subsequently relapse due to persisting chemoresistant cells indistinguishable from normal hematopoietic progenitors by conventional morphologic analysis, i.e., minimal residual disease (MRD) (1)(2)(3). In both childhood and adult AML, MRD is a powerful and independent prognostic factor (4-13).…”

Section: Introductionmentioning

confidence: 99%

Universal monitoring of minimal residual disease in acute myeloid leukemia

et al. 2018

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“…In AML, the best method of monitoring MRD is still a matter of debate. In some patients, leukemic cells show specific chromosomal rearrangements, which are detectable by PCR or FISH (5)(6)(7)(8)(9)(10). Flow cytometry can be used to detect a combination of antigens present on leukemic cells.…”

Section: Introductionmentioning

confidence: 99%

Prospective Validation of a New Method of Monitoring Minimal Residual Disease in Childhood Acute Myelogenous Leukemia

Steinbach

Bader

Willasch

et al. 2015

Clinical Cancer Research

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Purpose: This study evaluated the prognostic impact of a novel, simple, and standardized assay for monitoring minimal residual disease (MRD) in pediatric acute myelogenous leukemia (AML).Experimental Design: The expression of seven leukemia-associated genes (WT1, PRAME, CCL23, GAGED2, MSLN, SPAG6, and ST18) was measured by TaqMan Low Density Arrays in 112 patients and 52 healthy controls. Patients were treated according to the multicenter study AML-BFM 2004. Samples were collected prospectively at standard time points. The laboratory that measured MRD was blinded to patient outcome.Results: Relapse-free survival (RFS) was 95% (N ¼ 19; SE ¼ 5%) if expression of all genes was down to normal on day 15, 63% (N ¼ 41; SE ¼ 8%) if expression was normalized on day 28, and 38% (N ¼ 21; SE ¼ 11%) in patients who still showed elevated expression on day 28. The prognostic impact of MRD remained significant (P ¼ 0.002) when patients were stratified for the AML-BFM 2004 risk group. Multivariate analysis identified the MRD risk group and day 28 cytology as the only independent prognostic factors. Patients with a cytologic nonremission on day 28, which was confirmed by MRD, had a dismal prognosis. Only 1 out of 8 patients survived without relapse.Conclusions: This novel method of monitoring MRD has a strong prognostic impact that is independent from established risk factors in childhood AML.

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“…8,9,34 In contrast, up to 95% of patients will have an aberrant immunophenotype available for MRD detection by MFC. 35 Thus, a single, standardized MFC panel can be uniformly applied to nearly all AML patients across all morphologic and cytogenetic sub-types with a level of sensitivity in the range of 10 − 3 -10 − 4 (refs 7,31). Furthermore, MFC detects leukemic cells showing any immunophenotypic deviation from normal hematopoietic precursors, including potential subclones with different immunophenotypic aberrancies than the original major blast population.…”

Section: Advantages Of Multi-color Flow Cytometry-based Mrd Detectionmentioning

confidence: 99%

Multi-color flow cytometric immunophenotyping for detection of minimal residual disease in AML: past, present and future

Jaso

Wang

Jorgensen

et al. 2014

Bone Marrow Transplant

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Current chemotherapeutic regimens achieve CR in a large percentage of patients with AML. However, relapse after CR remains a significant problem. The presence of leukemic cells at levels too low to be detected by conventional microscopy, termed minimal residual disease (MRD), has been associated with an increased risk of relapse and shortened survival. Detection of MRD requires the use of highly sensitive ancillary techniques. Multi-color flow cytometric immunophenotyping is a sensitive method for quick and accurate detection of MRD. Use of this method in patient management may result in lower rates of relapse and improved survival, and is an effective means of assessing novel therapeutic agents. This method can be used in the vast majority of patients with AML, regardless of the immunophenotypic, cytogenetic and molecular genetic abnormalities present. Unfortunately, conflicting data regarding optimum methods of measurement and reporting, as well as the expertize required to interpret results have limited broad application of this technique. We provide a broad overview of this technique, including its advantages and limitations, and discuss the methods employed at our institution. We also review several possible areas of future investigation. INTRODUCTION AML is characterized by clonal expansion of myeloid precursors in the BM, peripheral blood and/or extramedullary tissues. 1 Current treatment regimens achieve CR in the majority of adult patients; however, approximately 65% of patients develop relapsed disease. 2,3 Thus, there is a need to effectively identify which patients are at most risk for impending relapse. Low levels of leukemic cells, termed minimal residual disease (MRD), have been shown to correlate with an increased risk of relapse and shortened survival believed to be a major cause of relapse. 4 These cells are present at levels below the sensitivity of conventional microscopic examination and as such, their detection requires the use of sensitive ancillary techniques. Detection of MRD by multi-color flow cytometric immunophenotyping (MFC) has been shown to be useful in the detection and characterization of MRD. However, several important concepts must be understood in order to ensure optimal application of this technique in both the clinical and research settings so that the information provided can be translated into better patient outcomes.

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Should evaluation for minimal residual disease be routine in acute myeloid leukemia?

Cited by 34 publications

References 64 publications

Universal monitoring of minimal residual disease in acute myeloid leukemia

Universal monitoring of minimal residual disease in acute myeloid leukemia

Prospective Validation of a New Method of Monitoring Minimal Residual Disease in Childhood Acute Myelogenous Leukemia

Multi-color flow cytometric immunophenotyping for detection of minimal residual disease in AML: past, present and future

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