Residual Disease Monitoring in Childhood Acute Myeloid Leukemia by Multiparameter Flow Cytometry: The MRD-AML-BFM Study Group

Langebrake, Claudia; Creutzig, Ursula; Dworzak, Michael; Hrušák, Ondřej; Mejstříková, Ester; Griesinger, Frank; Zimmermann, Martin; Reinhardt, Dirk

doi:10.1200/jco.2005.05.4312

Cited by 134 publications

(93 citation statements)

References 19 publications

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“…In the recent MRD-AML-BFM Study Group, however, MRD did not increase the prognostic power of the well defined BFM risk factors (FAB subtype, cytogenetics and morphologically determined blasts at day 15). 2 Day 15 blast data were not available for the patients of this cohort and therefore, the additional discriminatory value of MRD to the day 15 blast count could not be established in this study.…”

Section: Mrd Is An Independent Prognostic Factormentioning

confidence: 94%

“…MRD positivity before second induction was associated with a more than twofold risk of relapse, although MRD levels were not a significant factor in multivariate analysis. 2 These data indicate that MRD may be of clinical significance in children with AML, but that optimal time points (TPs) and cutoff levels are dependent on the flowcytometric methodology and on the treatment protocol. In this study, we evaluated the clinical significance of MRD in pediatric AML patients enrolled into the identical United Kingdom Medical Research Council (MRC) AML12 and Dutch Childhood Oncology Group (DCOG) ANLL97 protocols.…”

Section: Introductionmentioning

confidence: 94%

“…[1][2][3][4][5][6][7][8][9] Most MRD studies in AML have focused on adults, and relatively little is known about the prognostic significance of MRD in childhood AML. Sievers et al 3 showed, in a retrospective flowcytometric MRD study, that the relative risk of relapse in MRD-positive pediatric AML patients was 2.8 times the risk of relapses in MRD-negative patients.…”

Section: Introductionmentioning

confidence: 99%

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Clinical significance of flowcytometric minimal residual disease detection in pediatric acute myeloid leukemia patients treated according to the DCOG ANLL97/MRC AML12 protocol

et al. 2010

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Analysis of minimal residual disease (MRD) in childhood acute myeloid leukemia (AML) may predict for clinical outcome. MRD levels were assessed by flowcytometric immunophenotyping in 94 children with AML enrolled into a single trial (United Kingdom Medical Research Council AML12 and similar Dutch Childhood Oncology Group ANLL97). An aberrant immunophenotype could be detected in 94% of patients. MRD levels after the first course of chemotherapy predicted for clinical outcome: 3-year relapse-free survival was 85% ± 8% (s.e.) for MRD-negative patients (MRDo0.1%), 64%±10% for MRDlow-positive patients (0.1%pMRDo0.5%) and only 14±9% for MRD-high-positive patients (MRDX0.5%; Po0.001), whereas overall survival was 95% ± 5%, 70% ± 10% and 40% ± 13%, respectively, (Po0.001). Multivariate analysis allowing for age, karyotype, FLT3-internal tandem duplications and white blood cell count at diagnosis showed that MRD after the first course of chemotherapy was an independent prognostic factor. Although comparison of paired diagnosis-relapse samples (n ¼ 23) showed immunophenotypic shifts in 91% of cases, this did not hamper MRD analysis. In conclusion, flowcytometric MRD detection is possible in children with AML. The level of MRD after the first course of chemotherapy provides prognostic information that may be used to guide therapy.

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Section: Mrd Is An Independent Prognostic Factormentioning

confidence: 94%

Section: Introductionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

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Clinical significance of flowcytometric minimal residual disease detection in pediatric acute myeloid leukemia patients treated according to the DCOG ANLL97/MRC AML12 protocol

et al. 2010

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“…Hence, there is a clear trend to use MRD end-points for better risk stratification and treatment selection in pediatric and adult AML (6,32,33,35,36). Flow cytometry is the technical approach which has the broadest applicability and least need for a per patient test individualization among all currently available methods.…”

Section: Discussionmentioning

confidence: 99%

Blast cell deficiency of CD11a as a marker of acute megakaryoblastic leukemia and transient myeloproliferative disease in children with and without Down syndrome

Boztug

Schumich

Pötschger

et al. 2013

Cytometry Part B Clinical

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“…4,17,24,25,[27][28][29][30][31][32][33] Overall, these studies demonstrate that MFC-detected MRD is prognostically significant in virtually all AML patients over a wide array of patient populations and treatment strategies (Table 4). However, direct comparison of these studies is limited by variation in methodology, thresholds of positivity, patient population and treatment strategies.…”

Section: Prognostic Significance Of Multi-color Flow Cytometry-based mentioning

confidence: 92%

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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Residual Disease Monitoring in Childhood Acute Myeloid Leukemia by Multiparameter Flow Cytometry: The MRD-AML-BFM Study Group

Cited by 134 publications

References 19 publications

Clinical significance of flowcytometric minimal residual disease detection in pediatric acute myeloid leukemia patients treated according to the DCOG ANLL97/MRC AML12 protocol

Clinical significance of flowcytometric minimal residual disease detection in pediatric acute myeloid leukemia patients treated according to the DCOG ANLL97/MRC AML12 protocol

Blast cell deficiency of CD11a as a marker of acute megakaryoblastic leukemia and transient myeloproliferative disease in children with and without Down syndrome

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

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