The Role of Multiparameter Flow Cytometry for Detection of Minimal Residual Disease in Acute Myeloid Leukemia

Al-Mawali, Adhra; Gillis, David; Lewis, Ian D.

doi:10.1309/ajcp5tsd3dzxflcx

Cited by 110 publications

(101 citation statements)

References 53 publications

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“…Recent studies assessing minimal residual disease (MRD) have highlighted the limitations of morphology for reliable determination of remission status and several studies have shown that MRD status independently predicts disease relapse after antileukemia treatment. [11][12][13][14] Multiparametric flow cytometry (MFC) has been successfully used to quantify MRD in AML expressing leukemia-associated phenotypes. 13,15 Previous studies have demonstrated that MRD detectable by MFC is a powerful, independent predictor of subsequent relapse and shorter survival for AML patients in complete remission and can be used to risk-stratify both younger and older patients after chemotherapy and following HCT.…”

Section: Introductionmentioning

confidence: 99%

Pre-transplantation minimal residual disease with cytogenetic and molecular diagnostic features improves risk stratification in acute myeloid leukemia

et al. 2016

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Section: Introductionmentioning

confidence: 99%

Pre-transplantation minimal residual disease with cytogenetic and molecular diagnostic features improves risk stratification in acute myeloid leukemia

et al. 2016

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“…MFC is then used to document either the disappearance or persistence of the LAPs while simultaneously allowing the enumeration of aberrant cells. 19 While this method has been successfully used in several recent studies (Table 4), multiple issues limit its utility for clinical diagnosis.…”

Section: Multi-color Flow Cytometry-based Detection Of Mrd In Amlmentioning

confidence: 99%

“…Variations in pre-analytic factors such as sequence of antibody addition and incubation times may also affect results. 19 Furthermore, the appearance of MRD on MFC can be subtle, with abnormal cells showing a spectrum of antigen expression intensity overlapping with that of regenerating normal precursors, introducing a certain amount of subjectivity to interpretation and reporting. 19 In fact, studies have shown that interpretation of aberrations can be operator dependent.…”

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

confidence: 99%

“…19 Furthermore, the appearance of MRD on MFC can be subtle, with abnormal cells showing a spectrum of antigen expression intensity overlapping with that of regenerating normal precursors, introducing a certain amount of subjectivity to interpretation and reporting. 19 In fact, studies have shown that interpretation of aberrations can be operator dependent. 39 The European LeukemiaNet group has published recommendations regarding standardized pre-analytical steps and antibody combinations for the flow cytometric evaluation of acute leukemia.…”

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

confidence: 99%

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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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“…2 The major obstacle in MRD detection by RT-PCR or quantitative PCR (RQ-PCR) is represented by the limited percentage of AML patients presenting with detectable genetic aberrations. 3 The use of alternative markers for MRD detection suitable in the vast majority of AML patients, and in particular to test WT1 expression as a universal marker of leukemic cells. 2 The Wilms tumor gene (WT1.)…”

Section: Introductionmentioning

confidence: 99%

New Insight Towards Prognosis in Pediatric Acute Myeloid Leukemia: Comparative Study.

Ibrahim¹

2015

UHOD

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Wilms tumor gene (WT1) is a reliable marker for minimal residual disease assessment in acute leukemia children. This study was designed to demonstrate the potential use of WT1 to establish quality of remission in acute leukemia children for early identification of children at high risk of relapse. This study based on a quantitative Real-Time polymerase chain reaction (PCR) (TaqMan) assay in bone marrow samples collected from 45 acute myeloid leukemia children at diagnosis and during follow-up was established. Our results revealed, there was no significant association between WT1expression,at diagnosis, and either of gender, organomegally, total leucocytic count (TLC), French-American-British system (FAB) subtypes, CD34 expression, cytogenetic studies, percentage of blast infiltration or response to induction therapy. By comparing the results obtained at day 14 and those obtained at day 28, we cannot depend on WT1gene expression or MRD detection at day14 in predicting resistance to treatment or predicting mortality (p= 0.12). In contrast WT1 gene expression or MRD detection values after induction therapy (at day28) is an independent prognostic risk factor of relapse (p= 0.001) and death (p= 0.001). The blast percentage was significantly correlated to the WT1expression levels at day 28.The presence of MRD or WT1gene expression at the end of induction therapy is an extremely powerful adverse prognostic factor.WT1 at presentation has no prognostic significance whereas a high WT1 expression after induction therapy is a predictor for poor outcome. A rise inWT1expression during treatment is a predictor for relapse. WT1 expression is a valuable and important tool for MRD study in AML and the presence of MRD value at the end of induction therapy is an extremely powerful adverse prognostic factor despite of achievement of morphological remission.Keywords: Wilms tumor gene 1, Acute myeloid leukemia, Minimal residual disease ÖZET Pediatrik Akut Miyeloid Lösemi Prognozunu Anlamada Yeni Görüşler: Karşılaştırmalı ÇalışmaAkut çocukluk dönemi lösemilerde minimal rezidüel hastalığı göstermede Wilms tümör geni (WT1) güvenli bir belirteçtir. Bu çalışma yüksek riskli akut lösemili çocuklarda remsiyon kalitesini ve erken relapsları göstermede WT1 kullanımının potansiyel yerini araştırmak için planlanmıştır. Bu çalışmada 45 akut myeloid lösemili çocuk hastanın Real-Time polimeraz zincir reaksiyonu (PCR) (TaqMan) testi kullanılarak tanı anı ve takip kemik iliği örnekleri incelenmiştir. Çalışmamızın sonuçlarında; tanı anında WT1 ekspresyonu ile cinsiyet, organomegali, toplam lökosit sayısı, FAB sınıflaması alt tipi, CD34 ekspresyonu, sitogenetik çalışmalar, tanı anındaki blast oranı ve indüksiyon tedavisine yanıt arasında herhangi bir ilişki saptanamamıştır. 14. gün ve 28. gün örnekleri değerlendrildiğinde; 14. gün örneklerinde bakılan WT1 gen ekspresyonunun veya minimal rezidüel hastalık (MRD) tedaviye direnç veya mortaliteyi saptamada güvenili bir yöntem olmadığı gösterilmiştir (p= 0.12). Ancak indüksiyon tedavisi sonrası (28....

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The Role of Multiparameter Flow Cytometry for Detection of Minimal Residual Disease in Acute Myeloid Leukemia

Cited by 110 publications

References 53 publications

Pre-transplantation minimal residual disease with cytogenetic and molecular diagnostic features improves risk stratification in acute myeloid leukemia

Pre-transplantation minimal residual disease with cytogenetic and molecular diagnostic features improves risk stratification in acute myeloid leukemia

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

New Insight Towards Prognosis in Pediatric Acute Myeloid Leukemia: Comparative Study.

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