Immunophenotypic differences between diagnosis and relapse in childhood AML: Implications for MRD monitoring

Langebrake, Claudia; Brinkmann, Iris; Teigler‐Schlegel, Andrea; Creutzig, Ursula; Griesinger, Frank; Puhlmann, Ulrike; Reinhardt, Dirk

doi:10.1002/cyto.b.20037

Cited by 81 publications

(64 citation statements)

References 28 publications

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“…Comparable data have been reported in adult AML patients (90%) 19 and in a recent pediatric AML study (88%). 20 Furthermore, in common with the study by Langebrake et al, 20 we observed that the immature markers CD34, CD117 and HLA-DR were more frequently gained, whereas the differentiation markers CD14, CD11b and CD15 were more frequently lost at relapse, suggesting that the immunophenotype of the leukemic population at relapse was more immature.…”

Section: Stability Of Laip Between Diagnosis and Relapsesupporting

confidence: 86%

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: Stability Of Laip Between Diagnosis and Relapsesupporting

confidence: 86%

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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“…22 Although we do not have data on CD33 status at relapse, it seems unlikely that a shift in CD33 expression is the cause of the failure of GO to prevent relapse in this trial.…”

Section: Remission Achievedmentioning

confidence: 81%

Gemtuzumab ozogamicin as postconsolidation therapy does not prevent relapse in children with AML: results from NOPHO-AML 2004

Hasle

Abrahamsson²,

Forestier

et al. 2012

Blood

102

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“…20 These changes frequently involve increases in expression levels of myeloid (CD13, CD33) and stem cell antigens (CD34, CD117). 20,21 In one study, 98% of patients had an aberrant blast population at relapse that was not noted in the original diagnostic specimen. 21 Such changes are referred to as 'population shifts'.…”

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

confidence: 99%

“…20,21 In one study, 98% of patients had an aberrant blast population at relapse that was not noted in the original diagnostic specimen. 21 Such changes are referred to as 'population shifts'. These changes may be due to simple antigenic instability in the original leukemic clone, expansion of a preexisting small subclone and/or emergence of a new clone.…”

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

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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Immunophenotypic differences between diagnosis and relapse in childhood AML: Implications for MRD monitoring

Cited by 81 publications

References 28 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

Gemtuzumab ozogamicin as postconsolidation therapy does not prevent relapse in children with AML: results from NOPHO-AML 2004

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

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