| 1. |
- Björklund, Elisabet, et al.
(författare)
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Quality control of flow cytometry data analysis for evaluation of minimal residual disease in bone marrow from acute leukemia patients during treatment.
- 2009
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Ingår i: Journal of pediatric hematology/oncology : official journal of the American Society of Pediatric Hematology/Oncology. - : Lippincott Williams & Wilkins. - 1536-3678 .- 1077-4114. ; 31:6, s. 406-15
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Tidskriftsartikel (refereegranskat)abstract
- Low levels of leukemia cells in the bone marrow, minimal residual disease (MRD), are considered to be a powerful indicator of treatment response in acute lymphatic leukemia (ALL). A Nordic quality assurance program, aimed on standardization of the flow cytometry MRD analysis, has been established before implementation of MRD at cutoff level 10 as one of stratifying parameters in next Nordic Society of Pediatric Hematology and Oncology (NOPHO) treatment program for ALL. In 4 quality control (QC) rounds 15 laboratories determined the MRD levels in 48 follow-up samples from 12 ALL patients treated according to NOPHO 2000. Analysis procedures were standardized. For each QC round a compact disc containing data in list-mode files was sent out and results were submitted to a central laboratory. At cutoff level 10, which will be applied for clinical decisions, laboratories obtained a high concordance (91.6%). If cutoff level 10 was applied, the concordance would be lower (85.3%). The continuing standardization resulted in better concordance in QC3 and QC4 compared with QC1 and QC2. The concordance was higher in precursor B as compared with T-cell ALL. We conclude that after standardization, flow cytometry MRD detection can be reliably applied in international, multicenter treatment protocols.
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| 2. |
- Thörn, Ingrid, 1957-, et al.
(författare)
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Minimal residual disease assessment in childhood acute lymphoblastic leukemia : Results of a Swedish multi-centre study comparing real-time PCR and multi-colour flow cytometry
- 2009
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- In this Swedish multi-center study of early treatment response in childhood acute lymphoblastic leukemia (ALL), we evaluated the concordance between multicolour flow cytometry (FCM) and real-time quantitative polymerase chain reaction (RQ-PCR) for assessment of minimal residual disease (MRD). Multiple time points (i.e. day 15, 29, 50 and 106) were evaluated with the NOPHO (Nordic Society of Pediatric Hematology and Oncology) ALL 2000 treatment protocol as backbone. During 2002-2006, 334 children were diagnosed with ALL, where 228 had paired samples taken at any of the four time points. With the detection level of 0.1%, the concordance between RQ-PCR and FCM was 90% in the 726 paired samples analyzed. At day 29, the correlation between the methods was greater with MRD levels >0.1% (rs=0.7, p<0.001) than below (rs=0.2, p=0.024). MRD levels higher than 0.1% at day 29 was a significant predictor of higher risk of having a bone marrow relapse. This was true both for BCP ALL and T-ALL analysed with either FCM or RQ-PCR, although RQ-PCR was a better discriminator than FCM in T-ALL. However, using the NOPHO ALL 2000 protocol, our data indicate that a higher cut-off value (0.2%) should be applied in BCP ALL when using RQ-PCR as MRD method. In contrast, MRD levels ≥ 0.1%, analysed with either method late during induction therapy, was not a predictor of isolated extramedullary relapse. We therefore conclude that MRD assessment by RQ-PCR based IG/TCR rearrangement and multicolour FCM monitoring can be used as a clinical tool if the aim is to find childhood ALL cases with increased risk of having bone marrow relapses.
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| 3. |
- Thörnerup, Ingrid, et al.
(författare)
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Minimal residual disease assessment in childhood acute lymphoblastic leukaemia: a Swedish multi-centre study comparing real-time polymerase chain reaction and multicolour flow cytometry.
- 2011
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Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 152:6, s. 743-753
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Tidskriftsartikel (refereegranskat)abstract
- Minimal residual disease (MRD) assessment is a powerful prognostic factor for determining the risk of relapse in childhood acute lymphoblastic leukaemia (ALL). In this Swedish multi-centre study of childhood ALL diagnosed between 2002 and 2006, the MRD levels were analysed in 726 follow-up samples in 228 children using real-time quantitative polymerase chain reaction (RQ-PCR) of rearranged immunoglobulin/T-cell receptor genes and multicolour flow cytometry (FCM). Using an MRD threshold of 0·1%, which was the sensitivity level reached in all analyses, the concordance between RQ-PCR and FCM MRD values at day 29 was 84%. In B-cell precursor ALL, an MRD level of ≥0·1% at day 29 predicted a higher risk of bone marrow relapse (BMR) with both methods, although FCM was a better discriminator. However, considering the higher median MRD values achieved with RQ-PCR, a higher MRD cut-off (≥0·2%) improved the predictive capacity of RQ-PCR. In T-ALL, RQ-PCR was notably superior to FCM in predicting risk of BMR. That notwithstanding, MRD levels of ≥0·1%, detected by either method at day 29, could not predict isolated extramedullary relapse. In conclusion, the concordance between RQ-PCR and FCM was high and hence both methods are valuable clinical tools for identifying childhood ALL cases with increased risk of BMR.
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