Article

Stability of leukemia-associated immunophenotypes in precursor B-lymphoblastic leukemia/lymphoma: a single institution experience.

University of Texas Southwestern Medical School, Dallas, TX, USA.
American Journal of Clinical Pathology (Impact Factor: 3.01). 02/2007; 127(1):39-46. DOI: 10.1309/7R6MU7R9YWJBY5V4
Source: PubMed

ABSTRACT Essentially all cases of precursor B-lymphoblastic leukemia/lymphoma (B-ALL) demonstrate multiple immunophenotypic aberrancies relative to normal maturing B-cell precursors (hematogones). The stability of these aberrancies has relevance to follow-up minimal residual disease analysis. We compared the immunophenotypes at diagnosis and relapse in 51 childhood and adult B-ALLs with flow cytometry (FC) using broad antibody panels. A total of 446 aberrancies were present at diagnosis (median, 9 per case; range, 2-14). All cases retained multiple aberrancies at relapse (median, 8 per case; range, 2-14). Antibody panels at relapse allowed assessment of 383 (85.9%) of the initial 446 aberrancies. Of these, 299 (78.1%) were persistent and 84 (21.9%) were lost at relapse. Overall, 73% of cases showed a loss of at least 1 aberrancy at relapse. However, new aberrancies were detected in 60% of cases. These findings suggest that FC is suitable for the detection of residual B-ALL, provided that follow-up studies are not too narrowly targeted.

0 Bookmarks
 · 
60 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Detection of minimal residual disease (MRD) by flow cytometry (FCM) in B lymphoblastic leukemia (B ALL) is important for guiding patient specific clinical management. We describe apparent expression of CD19 by natural killer (NK) cells as a potential confounder in the detection of B ALL MRD by FCM. This finding was noted in seven different patient samples analyzed on different days as part of routine clinical care in our laboratory, with analysis of different anti-CD19 antibody clones and fluorochrome conjugates in five of the seven samples. Although the etiology of this finding is not clear, possibilities include true low level expression and trogocytosis. We highlight this finding to avoid potential misinterpretation when evaluating samples for MRD in patients with B lineage neoplasms, particularly in B ALL. © 2014 Clinical Cytometry Society.
    Cytometry Part B Clinical Cytometry 03/2015; 88(2). DOI:10.1002/cytob.21179 · 2.23 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Immunophenotyping has become essential to the diagnosis and the treatment management of acute lymphoblastic leukaemia (ALL). We prospectively studied minimal residual disease (MDR) in patients with B lineage ALL who achieved mCR remission. The initial series of patients consisted on 90 cases with B ALL. Sixty-Six patients had bone marrow samples adequate for MDR studies collected on day 35 of remission induction chemotherapy. Strategy of monitoring MRD is based on flow cytometry using quadruple staining according the leukaemia associated immunophenotype found at diagnosis. Data analysis was done using an EPI XL cytometer (Coulter), acquiring 500 000 events. Of the 66 patients 40 (60, 6%) had MRD 0, 01%. B lymphoblasts of ALL may morphologically resemble to hematogones (B benign lymphocyte precursors) and their immunophentypes have similarities. Different combinations of antibodies are tested to determine which combinations are more suitable to detect B residual leukaemics cells. The results of this present study indicate that: CD10/CD38/CD19/CD45 and CD10/CD34CD19/CD45 are the more specifics and should be used to distinguish B lymphoblasts of lymphoblastic acute leukaemia from normal hematogones.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Purpose: High-throughput sequencing (HTS) of immunoglobulin heavy chain genes (IGH) in unselected clinical samples for minimal residual disease (MRD) in B lymphoblastic leukemia (B-ALL) has not been tested. As current methods for MRD detection, such as flow cytometry or patient-specific qPCR are complex or difficult to standardize in the clinical laboratory, sequencing may enhance clinical prognostication. Experimental design: We sequenced IGH in paired pre- and day 29 post-treatment samples using residual material from consecutive, unselected samples from Children's Oncology Group AALL0932 trial to measure MRD as compared to flow cytometry. We assessed the impact of on-going recombination at IGH on MRD detection in post-treatment samples. Lastly, we evaluated a subset of cases with discordant MRD results between flow cytometry and sequencing. Results: We find clonal IGH rearrangements in 92 of 98 pre-treatment patient samples. Further, while on-going recombination of IGH was evident, index clones typically prevailed in MRD-positive post-treatment samples, suggesting that clonal evolution at IGH does not contribute substantively to tumor fitness. MRD was detected by sequencing in all flow cytometry positive cases with no false negative results. Additionally, in a subset of patients, MRD was detected by sequencing, but not by flow cytometry, including a fraction with MRD levels within the sensitivity of flow cytometry. We provide data that suggest that this discordance in some patients may be due to the phenotypic maturation of the transformed cell. Conclusion: Our results provide strong support for high-throughput sequencing of IGH to enhance clinical prognostication in B-ALL.
    Clinical Cancer Research 06/2014; 20(17). DOI:10.1158/1078-0432.CCR-13-3231 · 8.19 Impact Factor

Preview

Download
0 Downloads
Available from