HEMATOPATHOLOGYOriginal Article
I m p r o v e m e n t o f t h e C h r o n i c L y m p h o c y t i c L e u k e m i a S c o r i n g S y s t e m W i t h t h e M o n o c l o n a l A n t i b o d y S N 8 ( C D 7 9 b )ELISABETH J. A scoring system, based on the immunophenotypic analysis of a panel of five membrane markers (CD5, CD22, CD23, FMC7, Smlg) was shown to be useful in the distinction between chronic lymphocytic leukemia (CLL) and other B-cell lymphoproliferative diseases (non-CLL). We investigated whether the monoclonal antibody SN8 (CD79b) could improve our previous scoring system. Peripheral blood samples of 298 patients with CLL and 166 patients with non-CLL were analyzed by flow cytometry. Using the five standard markers, the accuracy of the scoring system was 91.8%, using a cutoff of 4The use of cell markers in the diagnosis of B-cell lymphoproliferative disorders has an important role in the distinction between chronic lymphocytic leukemia (CLL) and other chronic B-cell disorders.
1-2We have proposed 3 a scoring system based on flow cytometry analysis of five membrane markers: CD5, CD22, CD23, FMC7, and Smlg. A value of 1 or 0 was given for each marker to represent whether it is typical or atypical, respectively, for CLL. The most common immunophenotype profile observed in CLL is the following: CD5, positive; CD22, weak or negative; CD23, positive; FMC7, negative; and Smlg, weak. While most CLL cases have a score of 4 or 5, most non-CLL cases have a score of less than 3. points or higher, to distinguish CLL from non-CLL. This was increased to 96.6% if SN8 was added and a cutoff of 4 points or higher was also used. A similar accuracy, 96.8%, was observed if CD22 was excluded and a cutoff of 3 points or higher was used. Thus, the replacement of CD22 by SN8 in the original scoring system significantly increases its potential to discriminate between CLL and other B-cell lymphoproliferative diseases.
The clinical course of patients with chronic lymphocytic leukemia (CLL) is heterogeneous with some patients requiring early therapy whereas others will not be treated for years. The evaluation of an individual CLL patient's prognosis remains a problematic issue. The presence or absence of somatic mutations in the IgVH genes is currently the gold-standard prognostic factor, but this technique is labor intensive and costly. Genomic studies uncovered that 70 kDa zeta-associated protein (ZAP-70) expression was associated with unmutated IgVH genes and ZAP-70 protein expression was proposed as a surrogate for somatic mutational status. Among the available techniques for ZAP-70 detection, flow cytometry is most preferable as it allows the simultaneous quantification of ZAP-70 protein expression levels in CLL cells
The presence of minimal residual disease (MRD) by multiparametric flow cytometry (MFC) has been associated with adverse outcomes in AML patients treated with chemotherapy alone, but its impact in the setting of allogeneic hematopoietic SCT (HSCT) is less clear. We studied 88 patients who underwent myeloablative (MA) or reduced-intensity conditioned allogeneic HSCT for AML in first or subsequent remission at our center. MRD status was determined using three-color MFC on pre-HSCT BM aspirates, and patients were stratified by MRD status into MRD-negative, low-level MRD-positive (o1%) or high-level MRD-positive groups (1-4.9%). Two-year survival estimates in these groups were 66.8%, 51% and 30%, respectively (P ¼ 0.012), and 2-year estimates of relapse were 7.6, 37 and 70% (Po0.001). Pre-HSCT MRD was related to disease characteristics including secondary AML (P ¼ 0.002) and primary induction failure (P ¼ 0.005), but, despite these strong correlations, MRD remained independently associated with poorer survival in multivariate analysis (hazard ratio, 1.92; P ¼ 0.014). Pre-HSCT MRD is associated with adverse clinical outcomes in AML patients undergoing reduced-intensity or MA HSCT in first or subsequent remission and should be integrated into transplant strategies for patients with AML.
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