scholarly journals An Extensive Quality Control and Quality Assurance (QC/QA) Program Significantly Improves Inter-Laboratory Concordance Rates of Flow-Cytometric Minimal Residual Disease Assessment in Acute Lymphoblastic Leukemia: An I-BFM-FLOW-Network Report

Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 6148
Author(s):  
Margarita Maurer-Granofszky ◽  
Angela Schumich ◽  
Barbara Buldini ◽  
Giuseppe Gaipa ◽  
Janos Kappelmayer ◽  
...  
Keyword(s):  
Quality Control ◽  
Quality Assurance ◽  
Acute Lymphoblastic Leukemia ◽  
Minimal Residual Disease ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Control Measures ◽  
Disease Assessment ◽  
Quality Control Program ◽  
Minimal Residual

Monitoring of minimal residual disease (MRD) by flow cytometry (FCM) is a powerful prognostic tool for predicting outcomes in acute lymphoblastic leukemia (ALL). To apply FCM-MRD in large, collaborative trials, dedicated laboratory staff must be educated to concordantly high levels of expertise and their performance quality should be continuously monitored. We sought to install a unique and comprehensive training and quality control (QC) program involving a large number of reference laboratories within the international Berlin-Frankfurt-Münster (I-BFM) consortium, in order to complement the standardization of the methodology with an educational component and persistent quality control measures. Our QC and quality assurance (QA) program is based on four major cornerstones: (i) a twinning maturation program, (ii) obligatory participation in external QA programs (spiked sample send around, United Kingdom National External Quality Assessment Service (UK NEQAS)), (iii) regular participation in list-mode-data (LMD) file ring trials (FCM data file send arounds), and (iv) surveys of independent data derived from trial results. We demonstrate that the training of laboratories using experienced twinning partners, along with continuous educational feedback significantly improves the performance of laboratories in detecting and quantifying MRD in pediatric ALL patients. Overall, our extensive education and quality control program improved inter-laboratory concordance rates of FCM-MRD assessments and ultimately led to a very high conformity of risk estimates in independent patient cohorts.

scholarly journals Use of Minimal Residual Disease Assessment to Redefine Induction Failure in Pediatric Acute Lymphoblastic Leukemia

2017 ◽  
Vol 35 (6) ◽  
pp. 660-667 ◽  
Author(s):  
David O’Connor ◽  
Anthony V. Moorman ◽  
Rachel Wade ◽  
Jeremy Hancock ◽  
Ronald M.R. Tan ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Minimal Residual Disease ◽  
Chromosomal Abnormalities ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Disease Assessment ◽  
Pediatric Acute Lymphoblastic Leukemia ◽  
Real Time Quantitative Pcr ◽  
Induction Failure ◽  
Minimal Residual

Purpose Our aim was to determine the role of end-of-induction (EOI) minimal residual disease (MRD) assessment in the identification and stratification of induction failure in patients with pediatric acute lymphoblastic leukemia (ALL) and to identify genetic abnormalities that drive disease in these patients. Patients and Methods Analysis included 3,113 patients who were treated in the Medical Research Council UKALL2003 multicenter randomized trial (NCT00222612) between 2003 and 2011. MRD was measured by using standardized real-time quantitative PCR. Median follow-up was 5 years 9 months. Results Fifty-nine patients (1.9%) had morphologic induction failure with 5-year event-free survival (EFS) of 50.7% (95% CI, 37.4 to 64.0) and 5-year overall survival of 57.7% (95% CI, 44.2 to 71.2). Of these, a small proportion of patients with M2 marrow (6 of 44) and a low EOI MRD level (< 0.01%) had 5-year EFS of 100%. Conversely, among patients with morphologic remission 2.3% (61 of 2,633) had high MRD (≥ 5%) and 5-year EFS of 47.0% (95% CI, 32.9 to 61.1), which was similar to those with morphologic induction failure. Redefining induction failure to include morphologic induction failure and/or MRD ≥ 5% identified 3.9% (120 of 3,133 patients) of the trial cohort with 5-year EFS of 48.0% (95% CI, 39.3 to 58.6). Induction failure (morphologic or MRD ≥ 5%) occurred most frequently in T-ALL (10.1%; 39 of 386 T-ALL cases) and B-other ALL, that is, lacking established chromosomal abnormalities (5.6%; 43 of 772 B-other cases). Genetic testing within the B-other group revealed the presence of PDGFRB gene fusions, particularly EBF1-PDGFRB, in almost one third of B-other ALL cases. Conclusion Integration of EOI MRD level with morphology identifies induction failure more precisely than morphology alone. Prevalence of EBF1-PDGFRB fusions in this group highlights the importance of genetic screening to identify abnormalities that may be targets for novel agents.

Minimal Residual Disease Assessment and Risk-based Therapy in Acute Lymphoblastic Leukemia

2017 ◽  
Vol 17 ◽  
pp. S2-S9 ◽  
Author(s):  
Renato Bassan ◽  
Tamara Intermesoli ◽  
Annamaria Scattolin ◽  
Piera Viero ◽  
Elena Maino ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Minimal Residual Disease ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Disease Assessment ◽  
Minimal Residual

scholarly journals Immunological features of B-linear progenitors on the 15th day of acute lymphoblastic leukemia therapy in children. Comparison of minimal residual disease assessment protocols and own results

2020 ◽  
Vol 19 (1) ◽  
pp. 58-67
Author(s):  
O. A. Chernysheva ◽  
I. N. Serebryakova ◽  
N. A. Kupryshina ◽  
E. N. Sholokhova ◽  
M. A. Shervashidze ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Acute Lymphoblastic Leukemia ◽  
Minimal Residual Disease ◽  
Mononuclear Cells ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Disease Assessment ◽  
Main Research ◽  
First Time ◽  
Minimal Residual

Evaluation of minimal residual disease (MRD) on the 15th day of treatment of acute lymphoblastic leukemia from B-linear precursors (B-ALL) in children is of key importance in the prognosis of the disease. When evaluating the MRD, it is necessary to take into account the features of the primary immunophenotype of tumor B-lymphoblasts. To assess the MRD on the 15th day of treatment several immunological approaches have been proposed that have a general concept, but differ in fundamentally important details. The purpose of this work was to analyze the established flow cytometry (FC) protocols of the main research groups (BerlinFrankfurt-Munster Group, St. Jude Hospital, Children’s Oncology Group) and to compare the results evaluated according to those approaches. This study was approved by the Independent Ethical Committee N.N. Blokhin National Medical Cancer Research Center. The study included 131 patients with B-ALL aged 1 to 17 years (median 5.53). Pre-Pre-B immunosubvariant prevailed (92.4%). A morphological (myelogram count) and immunological (MRD assessment) study of the BM was performed in all patients on the 15th day. Comparing the FC protocols of the MRD on the 15th day, it was shown that CD10 was a more reliable criterion for the detection of B-LP in comparison with CD34. The expression of CD45 may serve as an additional criterion for the detection of B-LP. The recalculation of the mononuclear cells is a more stringent criterion for determining the MRD. The scientific novelty is that for the first time on the 15th day, a detailed comparison of flow cytometry data with a cytological picture of the bone marrow was carried out. It was shown for the first time that not all B-LP detected on the basis of CD10+ /CD19+ /CD34+ /CD45low are aberrant according to CD58/CD38.

Flow cytometry minimal residual disease assessment in peripheral blood of adult acute lymphoblastic leukemia patients.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e18517-e18517
Author(s):  
Alissa Minkovsky ◽  
Karry Charest ◽  
Ryan Schmidt ◽  
Debra Briggs ◽  
Daniel J. DeAngelo ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Acute Lymphoblastic Leukemia ◽  
Minimal Residual Disease ◽  
Peripheral Blood ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Accurate Determination ◽  
Disease Assessment ◽  
Extramedullary Relapse ◽  
Minimal Residual

e18517 Background: Multiparametric flow cytometry (FC) of bone marrow aspirate (BM) is a widely used method of minimal residual disease (MRD) assessment in acute lymphoblastic leukemia (ALL). In practice, ALL with hematogone-like phenotype and patients with recurrence of isolated extramedullary disease present challenges in accurate determination of MRD status. We hypothesized that addition of FC MRD of peripheral blood would aid in the interpretation of MRD status. Methods: 76 matched BM and PB specimens were analyzed independently for presence of ALL MRD by 6-color FC. Results: The overall rate of BM MRD-positivity was 24% (18/76) and PB was also MRD-positive in 22% (4/18) of BM-positive cases. PB MRD sensitivity and specificity relative to BM MRD was 13% [95% confident interval (CI) 2%-42%] and 98% [88-100%] for B-ALL samples (n = 65) and 67% [13%-98%] and 75% [36%-95%] for T-ALL samples (n = 11), respectively. We identified 2 cases with evidence of leukemic cells in PB at the time of the extramedullary relapse that were interpreted as MRD-negative in BM. Conclusions: PB MRD demonstrates high specificity with relatively low sensitivity, especially in B-ALL when compared to T-ALL. The use of combined PB and BM samples in MRD assessment by current FC methods may have added clinical and diagnostic value in patients with high risk of extramedullary relapse, including PB MRD as a non-invasive method for monitoring of systemic relapse.

scholarly journals Minimal Residual Disease Assessment and Allogeneic Transplantation As Consolidation Therapy in Acute Lymphoblastic Leukemia

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 7-8
Author(s):  
Jf Combariza ◽  
Leonardo Bautista Toloza ◽  
M Arango ◽  
L Diaz ◽  
Claudia Agudelo Lopez ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Minimal Residual Disease ◽  
De Novo ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Allogeneic Transplantation ◽  
Disease Assessment ◽  
Negative Group ◽  
First Remission ◽  
Minimal Residual

Minimal Residual Disease Assessment and Allogeneic Transplantation as Consolidation Therapy in Acute Lymphoblastic Leukemia Abstract Introduction: Detectable minimal residual disease (MRD) after therapy for acute lymphoblastic leukemia (ALL) is the strongest predictor of hematologic relapse (1-4). Colombian reports of adults with ALL showed poor survival rates, the median OS was 12 months and the median PFS was only 7 months (5,6). Most reports from Colombia as well as Latin America did not include patients that had a transplant as an initial consolidation strategy and used MRD as prognostic factor. (7-9). The objective of the study was to assess progression free survival (PFS) and overall survival (OS) of patients with ALL according with MRD status at end of induction therapy. Methods: A retrospective cohort comparing PFS and OS in adults with de novo ALL, according to the MRD status at the end of induction chemotherapy, and the type of post-induction consolidation strategy used. This research work had the endorsement of the ethics and research committees of the institutions where it was carried out. Results: Were included 165 adults with ALL in the MRD investigational group, the basal characteristics of the population are described in table 1.There were 73 patients in the MDR negative group and 92 in the MDR positive group. Median PFS for the MRD positive group was 11 months (CI 95% 11.7 - 22.2), and not reached for the MRD negative group (p&lt;0.001). At three-years PFS was 18% and 55 %, respectively (p&lt;0,001). Fig 1. The median OS for MRD positive patients was 16 months (CI 95%, 8.8 - 23.15) and was not reached in the MRD negative group. At three-years, OS was 26 % and 51 % for the former and latter group, respectively. Fig 2. Among subjects that were not transplanted, median PFS was 21 months for MRD negative and 9 months MRD positive patients (p&lt;0.001). Fig 3A. Median of PFS was not reached in either group, whereas 3-year PFS was 64% for MRD negative and 70% for MRD positive patients when transplantation in first remission was used (p=0.861). Fig 3B. For the patients with only chemotherapy for consolidation treatment, the median OS were 16 months (IC 95% 11.32 to 20.67) for MRD positive, and 27 months IC 95% (20.91 to 33.09) in negative MRD. (p=0.004). The 3-year OS 34% for MRD negative and 22% for MRD positive patients. Fig 4A. The individuals with allogeneic transplantation during first remission overcome de risk of death in the positive MRD status. The median OS were 16 months for positive MRD and transplantation and not reached in negative MRD group, The 3 year OS were 74% for MRD negative and 49% for MRD positive patients. (p=0.187). Fig 4B. Multivariate analysis At multivariate analysis, the Negative MRD status and transplantation in first remission were associated with better PFS and OS, in these patients with ALL de novo, Table 2. Conclusion: MRD status at end of induction is an independent prognostic factor for PFS and OS in adult ALL. Allogeneic transplantation in first remission may overcome the adverse prognostic impact MRD. This is the first report that verifies the impact of MRD, on progression free survival and overall survival in the Colombian population. Disclosures No relevant conflicts of interest to declare.

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