scholarly journals Prognostic Value of DNA Index By Flow Cytometry for Minimal Residual Disease in Childhood B-Cell Acute Lymphoblastic Leukemia

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5287-5287
Author(s):  
Elizabeth Cervantes ◽  
Daniel J Enriquez ◽  
Judith Vidal ◽  
Rosario Retamozo
Keyword(s):  
Flow Cytometry ◽  
Minimal Residual Disease ◽  
Prognostic Value ◽  
Conflicts Of Interest ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Critical Role ◽  
Induction Treatment ◽  
Dna Index ◽  
Minimal Residual

Abstract Background: Prognostic factors in B-ALL represent a critical role for treatment stratification. High hyperdiploids (>50 chromosomes) have been related to better outcomes, and hypodiploids to worse prognosis. DNA Index (DI) quantifies the DNA from leukemic blast by flow cytometry and has been correlated to the number of chromosomes. Our aim was to demonstrate the prognostic value of DI for minimal residual disease in childhood B-ALL. Methods: 26 blood samples from newly diagnosed childhood B-ALL cases were analyzed between November 2017 and February 2018. DI was evaluated by flow cytometry in samples with Propidium Iodide and leukemic blasts were identified by CD19/CD22/CD10/CD20 antibodies. DI was calculated as the ratio of mean fluorescence of pathologic B blasts and normal cells (T, NK lymphocytes, neutrophils and monocytes) in G0/G1 phase. We stablished three categories: diploid (0.95 - 1.05, 46 chromosomes), hypodiploid (<0.95) and hyperdiploid (>1.05). 8-colors FacsCanto II BD flow cytometer was also used to evaluate minimal residual disease with 0.0025% threshold of detection. Results: 26 cases were evaluated and 2 died during induction treatment. Median age was 8 years (4mo - 16years) and 54% were males. At diagnosis, 62% showed DI diploid and 38% DI hyperdiploid, no hypodiploids cases were detected. Clinical characteristics were similar between both groups. Median DI in the hyperdiploids cases was 1.25 (R: 1.12 - 1.64). We only detected two hyperdiploids cases by conventional karyotype. All patients received the same BFM-based protocol. After induction, all cases achieved complete remission and 46% had MRD negative at the 28th day. DI diploid and hyperdiploid cases achieved 47% and 44% MRD negative, respectively. At the end of consolidation (R: 6-8 Mo), 77% cases achieved MRD negative, and between categories, 62% of DI diploid cases had MRD negative and 100% of DI hyperdiploid cases were negative for MRD detection by flow (p=0.02). Conclusions: The hyperdiploid DNA index by flow cytometry is associated with minimal residual disease negative at the end of consolidation.Flow cytometry offers an alternative over the conventional karyotype to detect good prognosis groups among B-ALL cases. Disclosures No relevant conflicts of interest to declare.

scholarly journals Minimal Residual Disease (MRD) Assessed By Multi-Parameter Flow Cytometry (MFC) Is Highly Predictive of Outcome in Adult Patients with Acute Lymphoblastic Leukemia (ALL)

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1079-1079
Author(s):  
Farhad Ravandi ◽  
Jorgensen L Jeffrey ◽  
Deborah A. Thomas ◽  
Susan O'Brien ◽  
Elias Jabbour ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Minimal Residual Disease ◽  
Conflicts Of Interest ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Adult Population ◽  
Disease Free Survival ◽  
Cell Transplant ◽  
Platelet Recovery ◽  
Minimal Residual

Abstract Purpose - Predicting outcome in patients with ALL has been traditionally based on pre-treatment characteristics such as age, white blood cell count (WBC) and cytogenetics. Minimal residual disease is a surrogate to the complex interaction of disease biology and therapy and its role in assigning risk is well-established. Many prior studies in patients with ALL have used molecular markers of MRD with few studies evaluating the role of multi-parameter flow cytometry (MFC) in the adult population. We investigated the predictive value of MRD assessed by MFC among 340 patients with ALL treated between March 2004 and March 2014 using regimens including the hyperCVAD backbone. Methods - Among 340 patients with B-ALL treated in this period 323 (95%) achieved complete remission (CR) or CR without platelet recovery (CRp) and were included in this study. Median age was 52 (Range, 15-84). Median WBC was 9.35 x109/L (Range, 0.4-658.1 x109/L). Cytogenetics were normal in 62 (18%), Philadelphia+ in 146 (43%), 11q23/rearranged MLL in 14 (4%), aneuploid in 45 (13%), hyperdiploid in 29 (9%), hypodiploid in 13 (4%), insufficient metaphases/ not done in 31 (9%). MRD by MFC was assessed with a sensitivity of 0.01%, using a 15-marker, 4-color panel in the first half of the study and subsequently a 6-color panel. Bone marrow specimens for MRD assessment were obtained at the time of achievement of CR and at approximately 3 month intervals thereafter. Results - 260 patients had available samples at CR and 166 (64%) became MRD negative. Achieving MRD negative status at CR was associated with a statistically significant improvement in disease-free survival (P =0.004) and overall survival (P=0.03). 215 patients were evaluated for MRD at approximately 3 months and 201 (93%) became negative. Achieving MRD negative status at approximately 3 months was also associated with a statistically significant improvement in DFS (P=0.002) and OS (P=0.003). 166 patients were evaluated for MRD at approximately 6 months and 160 (96%) became negative. Achieving MRD negative status at approximately 6 months was also associated with a statistically significant improvement in DFS (P<0.0001) and OS (P<0.0001). Figure below demonstrates the DFS and OS by MRD status at CR (Figure 1a and 1b), at 3 months (Figure 2a and 2b), and at 6 months (Figure 3a and 3b) with patients censored at the time of undergoing an allogeneic stem cell transplant or last follow-up. On multivariate analysis including age, WBC at presentation, cytogenetics (standard vs. high risk), and MRD status at CR, 3 months and 6 months, achieving an MRD negative status at CR was an independent predictor of DFS (P<0.05). Conclusion – Achievement of an MRD negative state assessed by MFC is an important predictor of DFS and OS in patients with ALL Figure 1 Figure 1. Figure 2 Figure 2. Figure 3 Figure 3. Disclosures No relevant conflicts of interest to declare.

scholarly journals DNA Methylation Adds Prognostic Value to Minimal Residual Disease Status in Pediatric T‐Cell Acute Lymphoblastic Leukemia

2016 ◽  
Vol 63 (7) ◽  
pp. 1185-1192 ◽  
Author(s):  
Magnus Borssén ◽  
Zahra Haider ◽  
Mattias Landfors ◽  
Ulrika Norén‐Nyström ◽  
Kjeld Schmiegelow ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Minimal Residual Disease ◽  
Prognostic Value ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Disease Status ◽  
Cell Acute Lymphoblastic Leukemia ◽  
Minimal Residual

scholarly journals Marked Variability in Reported Minimal Residual Disease Lower Level of Detection of 4 Hematolymphoid Neoplasms: A Survey of Participants in the College of American Pathologists Flow Cytometry Proficiency Testing Program

2015 ◽  
Vol 139 (10) ◽  
pp. 1276-1280 ◽  
Author(s):  
Michael Keeney ◽  
Jaimie G. Halley ◽  
Daniel D. Rhoads ◽  
M. Qasim Ansari ◽  
Steven J. Kussick ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Chronic Lymphocytic Leukemia ◽  
Minimal Residual Disease ◽  
Plasma Cell ◽  
Myeloid Leukemia ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Lymphocytic Leukemia ◽  
Plasma Cell Myeloma ◽  
Minimal Residual

Context Flow cytometry is often applied to minimal residual disease (MRD) testing in hematolymphoid neoplasia. Because flow-based MRD tests are developed in the laboratory, testing methodologies and lower levels of detection (LODs) are laboratory dependent. Objectives To broadly survey flow cytometry laboratories about MRD testing in laboratories, if performed, including indications and reported LODs. Design Voluntary supplemental questions were sent to the 549 laboratories participating in the College of American Pathologists (CAP) FL3-A Survey (Flow Cytometry—Immunophenotypic Characterization of Leukemia/Lymphoma) in the spring of 2014. Results A total of 500 laboratories (91%) responded to the supplemental questions as part of the FL3-A Survey by April 2014; of those 500 laboratories, 167 (33%) currently perform MRD for lymphoblastic leukemia, 118 (24%) for myeloid leukemia, 99 (20%) for chronic lymphocytic leukemia, and 91 (18%) for plasma cell myeloma. Other indications include non-Hodgkin lymphoma, hairy cell leukemia, neuroblastoma, and myelodysplastic syndrome. Most responding laboratories that perform MRD for lymphoblastic leukemia reported an LOD of 0.01%. For myeloid leukemia, chronic lymphocytic leukemia, and plasma cell myeloma, most laboratories indicated an LOD of 0.1%. Less than 3% (15 of 500) of laboratories reported LODs of 0.001% for one or more MRD assays performed. Conclusions There is major heterogeneity in the reported LODs of MRD testing performed by laboratories subscribing to the CAP FL3-A Survey. To address that heterogeneity, changes to the Flow Cytometry Checklist for the CAP Laboratory Accreditation Program are suggested that will include new requirements that each laboratory (1) document how an MRD assay's LOD is measured, and (2) include the LOD or lower limit of enumeration for flow-based MRD assays in the final diagnostic report.

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