Flow cytometric follow-up of minimal residual disease in bone marrow gives prognostic information in children with acute lymphoblastic leukemia

Björklund, Elisabet; Mazur, James E.; Söderhäll, Stefan; Porwit‐MacDonald, Anna

doi:10.1038/sj.leu.2402736

Cited by 99 publications

(101 citation statements)

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“…[8][9][10][11][12][13][14] The goals of the subsequent common NOPHO ALL-2000 protocol were to examine the efficacy of Vincristine (VCR)/Dexamethasone reinductions during maintenance therapy and to examine the feasibility of non-centralized minimal residual disease (MRD) monitoring by flow cytometry and PCR. [15][16][17][18][19] The ALL-92 and ALL-2000 studies have paved the way to total elimination of prophylactic cranial irradiation in the current ALL-2008 protocol and to implementation of a treatment stratification primarily based on cytogenetics and early MRD monitoring. We here present the results of the NOPHO ALL-92 and ALL-2000 studies and our current strategy for treatment of childhood ALL.…”

Section: Introductionmentioning

confidence: 99%

Long-term results of NOPHO ALL-92 and ALL-2000 studies of childhood acute lymphoblastic leukemia

et al. 2009

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Analysis of 2668 children with acute lymphoblastic leukemia (ALL) treated in two successive Nordic clinical trials (Nordic Society of Paediatric Haematology and Oncology (NOPHO) ALL-92 and ALL-2000) showed that 75% of all patients are cured by first-line therapy, and 83% are long-term survivors. Improvements in systemic and intrathecal chemotherapy have reduced the use of central nervous system (CNS) irradiation to o10% of the patients and provided a 5-year risk of isolated CNS relapse of 2.6%. Improved risk stratification and chemotherapy have eliminated the previous independent prognostic significance of gender, CNS leukemia and translocation t(1;19)(q23;p13), whereas the post-induction level of minimal residual disease (MRD) has emerged as a new risk grouping feature. Infant leukemia, high leukocyte count, T-lineage immunophenotype, translocation t(4;11)(q21;q23) and hypodiploidy persist to be associated with lower cure rates. To reduce the overall toxicity of the treatment, including the risk of therapy-related second malignant neoplasms, the current NOPHO ALL-2008 protocol does not include CNS irradiation in first remission, the dose of 6-mercaptopurine is reduced for patients with low thiopurine methyltransferase activity, and the protocol restricts the use of hematopoietic stem cell transplantation in first remission to patients without morphological remission after induction therapy or with high levels of MRD after 3 months of therapy.

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Section: Introductionmentioning

confidence: 99%

Long-term results of NOPHO ALL-92 and ALL-2000 studies of childhood acute lymphoblastic leukemia

et al. 2009

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“…The flow cytometric method used has been described in Bjorklund et al 6 A stain and then lyse/wash technique was used. At diagnosis, leukemic blasts were immunophenotyped with triple or four-color immunofluorescence using fluorochrome-conjugated antibodies.…”

Section: Flow Cytometrymentioning

confidence: 99%

“…Flow cytometry can be applied to approximately 90% of ALL patients and can reach sensitivities of 10 À3 -10 À4 . 6,11,17,18 A few studies compared molecular methods and flow cytometry for MRD detection in ALL patients. 12,[19][20][21][22] Previously, these comparisons were hampered by the lack of sufficiently quantitative molecular methods.…”

Section: Introductionmentioning

confidence: 99%

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Analysis of minimal residual disease in childhood acute lymphoblastic leukemia: comparison between RQ-PCR analysis of Ig/TcR gene rearrangements and multicolor flow cytometric immunophenotyping

et al. 2004

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Detection of minimal residual disease (MRD) in follow-up samples from patients with ALL is essential for evaluation of treatment response. We applied multicolor flow cytometry and real-time quantitative PCR (RQ-PCR) to compare MRD results in 71 follow-up samples from 22 children treated for ALL. When results obtained by flow cytometry and RQ-PCR were grouped into positive-negative categories, a significant level of agreement was found in 72% of samples (Po0.001). However, if a cutoff level of 0.01% was applied, the concordance was 89%. MRD could be quantified in 19 samples by both methods, showing a strong correlation (Po0.01). Nevertheless, MRD levels differed more than five-fold between both methods in 4/ 19 samples. In 20 (28%) samples, the two techniques showed discordant results. Most discordant results (17/20) were due to the limited sensitivity of flow cytometry analysis within the range 0.01-0.001%; remaining discordant results were due to the instable or subclonal IG/TCR gene rearrangements or a limited quantitative range of the applied RQ-PCR targets. Although concordant results could be obtained by flow cytometry and RQ-PCR analysis, MRD levels may differ. Therefore, MRD data obtained by these two techniques are not yet easily exchangeable.

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“…MRD data were acquired and analyzed as previously described. 21 All the patients' parents were informed of the investigational nature of this study, and informed consent was obtained from each parent in accordance with the conditions of the approval of the study by the local ethics committee (Stockholm, Sweden).…”

Section: Patientsmentioning

confidence: 99%

Dexamethasone-induced apoptosis in acute lymphoblastic leukemia involves differential regulation of Bcl-2 family members

Laane¹,

Panaretakis²,

Pokrovskaja³

et al. 2007

Haematologica

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Flow cytometric follow-up of minimal residual disease in bone marrow gives prognostic information in children with acute lymphoblastic leukemia

Cited by 99 publications

References 46 publications

Long-term results of NOPHO ALL-92 and ALL-2000 studies of childhood acute lymphoblastic leukemia

Long-term results of NOPHO ALL-92 and ALL-2000 studies of childhood acute lymphoblastic leukemia

Analysis of minimal residual disease in childhood acute lymphoblastic leukemia: comparison between RQ-PCR analysis of Ig/TcR gene rearrangements and multicolor flow cytometric immunophenotyping

Dexamethasone-induced apoptosis in acute lymphoblastic leukemia involves differential regulation of Bcl-2 family members

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