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: 2.51). 02/2007; 127(1):39-46. DOI: 10.1309/7R6MU7R9YWJBY5V4
Source: PubMed


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.

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    • "It is conceivable that a false negative study could occur in the setting of a narrowly targeted antibody panel, in combination with loss of immunophenotypic aberrancies present at diagnosis . The ability of haematological malignancies to undergo immunophenotypic shifts has been well established, particularly in B-cell and myeloid neoplasms (Chen et al, 2007). However, data regarding immunophenotypic stability in T-LGLL is limited. "

    Full-text · Article · Oct 2010 · British Journal of Haematology
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    • "subsequent MRD detection in greater than 90% of cases of ALL [37], the stability of such leukemia-associated immunphenotypes has an impact on the likelihood of obtaining a falsely negative MRD result because of immunophenotypic drift or shift. Such changes in immunophenotype at relapse may occur [43] [44] [45], but they generally do not preclude the immunophenotypic detection of MRD, provided the use of multiple antibody combinations and an appropriate degree of flexibility in the analysis of the flow cytometric data [46] [47] [48] [49]. Because the detection of aberrant or leukemia-associated immunophenotypes requires at least prior knowledge of the composite immunophenotype (and, ideally, the original flow cytometric data to permit direct comparison), this approach to MRD detection is difficult in cases in which the diagnostic immunophenotypic data are not available at the time of the MRD assay. "
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    ABSTRACT: Flow cytometric immunophenotyping (FCI) is an important diagnostic modality in the evaluation of patients who have suspected or known acute lymphoblastic leukemia (ALL). It enables rapid identification, quantification, and immunophenotypic characterization of leukemic blasts, permitting accurate and timely diagnosis. Beyond facilitating the classification of ALL into fundamental diagnostic categories, FCI may anticipate recurrent cytogenetic and molecular abnormalities. FCI permits the detection of leukemic blasts after therapy at a level lower than that achievable by conventional microscopic examination. Flow cytometric detection of minimal residual disease is among the strongest prognostic factors in patients who have ALL and may provide an opportunity for more precise risk-adapted therapies.
    Preview · Article · Oct 2007 · Clinics in Laboratory Medicine
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    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.
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