Minimal residual disease evaluation by flow cytometry is a complementary tool to cytogenetics for treatment decisions in acute myeloid leukaemia

Vidriales, María‐Belén; Pérez-López, Estefanía; Pegenaute, Carlota; Castellanos, Marta; Pérez, José Antonio Martín; Chandía, Mauricio; Dı́az-Mediavilla, Joaquı́n; Rayón, Consuelo; Heras, Natalia de las; Fernández-Abellán, Pascual; Cabezudo, Miguel Ángel; Coca, Alfonso García de; Alonso, José M.; Olivier, C; Hernández-Rivas, Jesús M.; Montesinos, Pau; Fernández, Rosa; Suárez, J. García; García, María Inmaculada García; Sayas, María-José; González, Marcos; Órfão, Alberto; Miguel, Jesús F. San

doi:10.1016/j.leukres.2015.10.002

Cited by 32 publications

(24 citation statements)

References 41 publications

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“…It was deliberately chosen to run this study as an independent, blinded appreciation of the value of MFC MRD in AML. Because quite a number of patients were not enrolled in clinical trials, this also somehow confirms the strength of MRD as an independent prognostic tool, applicable in “real life” to any patient, a notion emerging in recent literature . It is also interesting that when considering a stratification of the patients into cytogenetically defined risk groups, MRD remained a potent significant stratifier and retained the highest statistical significance in multivariate analyses.…”

Section: Discussionsupporting

confidence: 93%

Prognostic value of multicenter flow cytometry harmonized assessment of minimal residual disease in acute myeloblastic leukemia

Lacombe

Campos

Allou

et al. 2017

Hematological Oncology

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The assessment of minimal residual disease (MRD) in acute myeloblastic leukemia is of growing interest as a prognostic marker of patients' outcome. Multiparameter flow cytometry (MFC), tracking leukemia-associated immunophenotypic patterns, has been shown in several studies to be a useful tool to investigate MRD. Here, we report a multicenter prospective study which allowed to define a harmonized analysis strategy, as well as the efficacy of MFC MRD to predict outcome. This study included 276 patients, in 10 different MFC centers, of whom 268 had at least 1 MRD check point. The combination of a CD45, CD34, and CD33 backbone, with the addition of CD117, CD13, CD7, and CD15 in 2 five-color tubes allowed to define each patient's multiparameter immunophenotypic characteristics at diagnosis, according to a Boolean combination of gates. The same individual diagnosis gating strategy was then applied at each MRD time point for each patient. MRD levels were stratified according to log by log thresholds, from 5 × 10 (the classical morphological threshold to define remission) down to <5 × 10 . MRD was found to be constantly negative (<5 × 10 ) for 148 patients. Survival analyses significantly associated MRD negativity with a good prognosis and any positive value with poorer outcome. All P values were <0.0001 both for disease-free and overall survival at the earliest time point (post-induction, MRD1) as well as when considering all time points together. Finally, MRD levels were independent of cytogenetics and allowed in fact to further stratify all cytogenetics risk groups. In summary, this multicenter study demonstrates that a simple combination of immunophenotypic markers successfully allows for the detection of MRD in acute myeloblastic leukemia patients, with a strong correlation to outcome.

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Section: Discussionsupporting

confidence: 93%

Prognostic value of multicenter flow cytometry harmonized assessment of minimal residual disease in acute myeloblastic leukemia

Lacombe

Campos

Allou

et al. 2017

Hematological Oncology

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“…Buccisano et al identified 0.035% as the MRD threshold related to the 5‐year estimated RFS and OS at postinduction and postconsolidation. San Muguel et al and Vidriales et al described a significantly different outcome among patients with MRD of <0.01%, 0.01‐0.1%, and >0.1%. Furthermore, Wood et al and Chang et al defined MRD positivity as containing any level of measurable residual disease and proved its outcome prediction value in patients with transplantation.…”

Section: Discussionmentioning

confidence: 94%

Identifying leukemia‐associated immunophenotype‐based individualized minimal residual disease in acute myeloid leukemia and its prognostic significance

et al. 2019

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Based on the leukemia-associated immunophenotypes (LAIPs), minimal residual disease (MRD) related to the outcome can be detected by multiparameter flow cytometry in acute myeloid leukemia (AML) patients. Although 0.1% was commonly used as a cutoff value, measurable MRD or MRD level below 0.1% has also been associated with prognostic significance and more sensitive thresholds (<0.1%) are required for improving AML prognosis prediction. In this study, 292 adult patients diagnosed with AML (non-M3) were enrolled, 36 kinds of LAIPs were identified, and the baseline expression levels in normal or regenerating bone marrows of each kind of LAIP were established, which ranged from <2.00 × 10 −5 to 5.71 × 10 −4 . The baseline level of each LAIP was considered as the individual threshold for MRD assessment. MRD statuses stratified by 0.1% and individual threshold were termed as 0.1%-MRD and individual-MRD, respectively. The patients of individual-MRD neg showed significantly better survival compared with those of 0.1%-MRD neg /individual-MRD pos or 0.1%-MRD pos . Multivariate analysis showed that when time points of complete remission, post the first and second consolidation courses, were considered, only individual-MRD post second consolidation presented independent prognostic value. Notably, in patients of cytogenetic/molecular low-risk (LR) or intermediate-risk (IR), the individual-MRD status could identify the patients with significantly different outcomes, while 0.1%-MRD status could not. Furthermore, among the patients of the LR or IR group which received chemotherapy only, those with individual-MRD neg status presented favorable survival, which was comparable with that of the patients accepted allogeneic hematopoietic stem cell transplantation (ASCT). This approach is useful in the selection of an ASCT strategy for clinical practice.

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“…Therefore, in MRD‐negative intermediate risk patients, it is possible that allo‐HSCT should be avoided . Similar conclusions could be drawn from an earlier study: In intermediate risk patients with MRD levels ≥0.01% in CR1, allo‐SCT improved outcome as compared to chemotherapy alone, whereas patients with <0.01% MRD did not benefit from allo‐HSCT . Interestingly, undetectable levels abrogated the risk for patients in the adverse genetic risk group in this study .…”

Section: Mfc As Tool To Guide Personalized Treatment In Amlmentioning

confidence: 99%

“…All these and more accumulated efforts have firmly established the prognostic role of MRD in CR1. Therefore, monitoring of MRD plays an increasingly important role in everyday practice for assessment of treatment response and risk stratification (24,47,85).…”

Section: Mrd As Tool To Predict Outcomementioning

confidence: 99%

Measurable residual disease testing for personalized treatment of acute myeloid leukemia

Ehinger

Pettersson

2019

APMIS

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This review summarizes – with the practicing hematologist in mind – the methods used to determine measurable residual disease (MRD) in everyday practice with some future perspectives, and the current knowledge about the prognostic impact of MRD on outcome in acute myeloid leukemia (AML), excluding acute promyelocytic leukemia. Possible implications for choice of MRD method, timing of MRD monitoring, and guidance of therapy are discussed in general and in some detail for certain types of leukemia with specific molecular markers to monitor, including core binding factor (CBF)‐leukemias and NPM1‐mutated leukemias.

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Minimal residual disease evaluation by flow cytometry is a complementary tool to cytogenetics for treatment decisions in acute myeloid leukaemia

Cited by 32 publications

References 41 publications

Prognostic value of multicenter flow cytometry harmonized assessment of minimal residual disease in acute myeloblastic leukemia

Prognostic value of multicenter flow cytometry harmonized assessment of minimal residual disease in acute myeloblastic leukemia

Identifying leukemia‐associated immunophenotype‐based individualized minimal residual disease in acute myeloid leukemia and its prognostic significance

Measurable residual disease testing for personalized treatment of acute myeloid leukemia

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