Prospective long-term minimal residual disease monitoring using RQ-PCR in RUNX1-RUNX1T1-positive acute myeloid leukemia: results of the French CBF-2006 trial

Willekens, Christophe; Blanchet, Odile; Renneville, Aline; Cornillet‐Lefèbvre, Pascale; Pautas, Cécile; Guièze, Romain; Ifrah, Norbert; Dombret, Hervé; Jourdan, Éric; Preudhomme, Claude; Boissel, Nicolas

doi:10.3324/haematol.2015.131946

Cited by 97 publications

(94 citation statements)

References 22 publications

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“…No clear superiority of one MRD technology over another in AML has been proven, with typically at least one hundred fold improvement in sensitivity compared with morphology alone, however flow cytometry methods may suffer from greater variability between centers than molecular approaches. 81 PCR-based monitoring of disease in the peripheral blood has been used successfully to monitor for patients with favorable risk AML for translocation(15;17), inversion(16) and translocation(8;21) AML 94-97 and more recently somatic mutations such as in NPM1 . 98 The ELN performed extensive testing on expression based MRD using WT1.…”

Section: Peripheral Blood Monitoringmentioning

confidence: 99%

Bone marrow evaluation for diagnosis and monitoring of acute myeloid leukemia

et al. 2017

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The diagnosis of acute myeloid leukemia (AML) can be made based on peripheral blood or bone marrow blasts. In this review, we will discuss the role of bone marrow evaluation and peripheral blood monitoring in the diagnosis, management, and follow up of AML patients. For patients with circulating blasts, it is reasonable to perform the necessary studies needed for diagnosis and risk stratification, including multiparametric flow cytometry, cytogenetics, and molecular analysis, on a peripheral blood specimen. The day 14 marrow is used to document hypocellularity in response to induction chemotherapy, but it is unclear if that assessmentis necessary as it often does not affect immediate management. Currently, response assessments performed at count recovery for evaluation of remission and measurable residual disease rely on bone marrow sampling. For monitoring of relapse, peripheral blood evaluation may be adequate, but the sensitivity of bone marrow testing is in some cases superior. While bone marrow evaluation can certainly be avoided in particular situations, this cumbersome and uncomfortable procedure currently remains the de facto standard for response assessment.

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Section: Peripheral Blood Monitoringmentioning

confidence: 99%

Bone marrow evaluation for diagnosis and monitoring of acute myeloid leukemia

et al. 2017

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“…Персистирование химер-ного гена RUNX1-RUNX1T1 на фоне костномозговой ремиссии, не приводящее к развитию костномозгового рецидива, описано разными исследователями [47]. По опубликованным в 2016 г. данным многоцентрового про-спективного французского исследования CBF-2006, из 96 пациентов в ремиссии CBF-ОМЛ у 9 % наблюдался МОБ-положительный статус в течение 2 лет без раз-вития рецидивов заболевания [30].…”

Section: Discussionunclassified

“…Медиана удвоения лейкозного клона CBFB-MYH11 была значимо больше (36 дней), чем клонов RUNX1-RUNX1T1 (14 дней), PML-RARA (12 дней) и NPM1 (11 дней) (p < 0,001). По данным других авторов, при утрате молекулярной ремиссии с выявлением уровня транскрипта более 0,5 % развитие костномозгового рецидива отмечалось в среднем через 28 дней (диапазон 10-99 дней) [30]. В случае выявления молекулярного рецидива необходимо повторное подтверждающее ис-следование.…”

Section: Discussionunclassified

“…За MОБ-отрицательные принимались образцы с количеством RUNX1-RUNX1T1 < 10 копий [29]. В ретроспективных исследованиях длительного наблю-дения на постконсолидационном этапе было показано, что определяемая MОБ-позитивность была связана с более высоким риском рецидива заболевания [30,31]. В то же время в целом ряде исследований была проде-монстрирована вероятность длительной ремиссии и при сохранении химерного гена RUNX1-RUNX1T1 [25,26,[32][33][34][35][36].…”

Section: Introductionunclassified

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Molecular Monitoring of RUNX1-RUNX1T1 Transcript Level in Acute Myeloblastic Leukemias on Treatment

Гиршова¹,

Ovsyannikova²,

Кузин³

et al. 2016

Клиническая онкогематология

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Background. The current approach to treatment of acute myeloblastic leukemia (AML) includes the achievement of maximum tumor reduction and, therefore, eradication of a leukemic clone. The goal of the therapy is to achieve undetectable levels of the target gene, except an isolated molecular rearrangement of RUNX1-RUNX1T1. Aim. To estimate the dynamics of the RUNX1-RUNX1T1 level and relevant clinical manifestations during the monitoring of various stages of the program therapy and after its completion. Methods. The article presents a description of 10 cases of AML with isolated RUNX1-RUNX1T1 expression (n = 4) and the expression in combination with different molecular and cytogenetic abnormalities (n = 6). In addition, a long-term monitoring of the gene expression by quantitative determination of RUNX1-RUNX1T1 using a real-time PCR was presented. Results. The incidence of relapses in a group with a decreased RUNX1-RUNX1T1 expression level of >2 log is 75 % as compared to patients with a less significant reduction of the transcript level (with the relapse incidence equal to 0 %) (p = 0.05). The increase of the RUNX1-RUNX1T1 level against the background of bone marrow remission by more than 1 log coincided with a bone marrow relapse within 5-18 weeks. In addition, long-term persistence of a certain transcript level after the completion of a program therapy without relapse is possible. Conclusion. The study analyzed possible molecular background of different clinical outcomes of long-term persistence of the RUNX1-RUNX1T1 transcript that might lead to an individualized approach to AML patients.

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“…Rising levels of molecular markers of MRD almost inevitably leads to relapse, be it after conventional cytoreductive therapy or in a post‐transplant setting. . Similar findings have been reported for rising MRD as determined by MFC .…”

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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Prospective long-term minimal residual disease monitoring using RQ-PCR in RUNX1-RUNX1T1-positive acute myeloid leukemia: results of the French CBF-2006 trial

Cited by 97 publications

References 22 publications

Bone marrow evaluation for diagnosis and monitoring of acute myeloid leukemia

Bone marrow evaluation for diagnosis and monitoring of acute myeloid leukemia

Molecular Monitoring of RUNX1-RUNX1T1 Transcript Level in Acute Myeloblastic Leukemias on Treatment

Measurable residual disease testing for personalized treatment of acute myeloid leukemia

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