Demonstration of the Clinical Performance of the ClearLLab LS in a Multi-Center Study
Diana B Careaga1, Guoyan Cheng1, Mike Keeney2, Joanne Luider3, Wolfgang Kern4, Gerard Lozanski5, Ben Hedley2, Lori Lowes2, Debbie Murphy3, Evelyn Karl 4, Rebecca Pearson5, Nicole Bergman5, Robert Magari1, Neha Girish6, Badri Natarajan6, Liliana Tejidor1
1Clinical Research, Beckman Coulter, Inc. Miami, FL 33196
2London Health Sciences Center. London, Ontario, Canada N6A 5W9
3Calgary Laboratory Services. Calgary, Alberta, Canada T2N 2T9
4MLL Munich Leukemia Laboratory. Munich, Germany 81377
5The Ohio State University. Columbus, Ohio 43210
6Bangalore Development Center, Bangalore, India 560058
Introduction
ClearLLab Lymphoid Screen (ClearLLab LS*) is a 12- antibody 10-color cocktail screening panel (Table 1) for leukemia and lymphoma immunophenotyping of normal and abnormal hematolymphoid cells from peripheral whole blood (WB) or bone marrow (BM) collected in K2EDTA, Heparin or ACD anticoagulants, or lymph node (LN) tissues. ClearLLab LS provided in the DURAClone dry reagent format supports qualitative results for the B, T and NK lineages, which should be interpreted along with additional clinical and laboratory findings.
Table 1. ClearLLab LS Panel. The ClearLLab LS is a 12 antibody 10-color cocktail screening tube provided in the DURAClone dry reagent format.
Materials & Methods
The clinical accuracy of the ClearLLab LS panel was evaluated by comparing to the cleared predicate panel ClearLLab reagents for primary agreement in detecting the presence or absence of abnormal populations from assessed specimens by flow cytometry. The targeted subjects were based on 2006 Bethesda International Consensus Recommendations[1], and only specimens from new cases or follow-up for lymphoid neoplasms were included. Furthermore, the study also evaluated the ability of the ClearLLab LS panel to correctly assess the maturity and lineage origin of the identified abnormal populations as compared to the predicate ClearLLab reagents panel. The overall study design was illustrated in Figure 2. Subjects were enrolled from four clinical sites across the United States, Canada and Europe. The principal investigators (PIs) at each site assessed the phenotype results independently for ClearLLab LS and ClearLLab reagents as per WHO guidelines[2], and were blind to the final clinical diagnosis of the subjects.
Figure 2. Clinical Study Design. Illustrated are the numbers for the primary and second endpoints designed for this clinical trial.
Results
A total of 210 subjects, including 108 males and 102 females, were enrolled for the study. Among them 118 (56%) subjects were clinically diagnosed with hematologic malignancies which include 80 B-cell neoplasms, 11 T/NK neoplasms and 27 myeloid neoplasms (Figure 3). The tested specimen types are from the WB (102 specimens), BM (77 specimens) and LN (31 specimens) reflecting the disease distribution and/or clinical indications encountered in the leukemia and lymphoma populations as per 2006 Bethesda International Consensus Recommendations and the American Cancer Society “Cancer Facts and Figures 2015”[3].
Figure 3. Study Demographics of Enrolled Subjects. In total 210 enrolled subjects, there are 118 malignant specimens as per clinical diagnosis, 68% are from B lineage, 23% are from myeloid lineage and 9% are from T lineage, including 39 cases of Non-Hodgkin’s lymphoma, 36 cases of chronic leukemia, 27 cases of acute leukemia and 16 cases of others (MDS, MPN and Plasma cell neoplasm).
Comparing the ClearLLab LS to the predicate ClearLLab reagents, there is 100% agreement in detecting the presence (designated as “positive”) or absence (designated as “negative”) of an abnormal population (Table 2). Additionally, the two panels had a 100% agreement for the designation of maturity of all the 106 identified abnormal populations, including 70 mature abnormal populations and 36 immature abnormal malignancies (Table 3). We also further compared the lineage assessment in the lymphoid abnormalities (B, T and NK) between these two panels (Figure 4). By using the ClearLLab LS, 100% agreement was confirmed in mature lymphoid malignancies (69 cases) with 99% agreement in all lymphoid malignancies (including 69 mature and 8 immature malignancies).
Table 2. Phenotype Agreement ClearLLab LS vs. ClearLLab Reagents. The ClearLLab LS 100% agreed with the ClearLLab reagents in detecting the presence (N=106) or absence (N=104) of an abnormal phenotype in a total of 210 tested specimens (left), with 95% confidence intervals provided (right).
Table 3. Maturity Agreement ClearLLab LS vs. ClearLLab Reagents. The ClearLLab LS 100% agreed with the ClearLLab reagents in assessing the maturity status of a total 106 identified abnormal populations (left), with 95% confidence intervals provided (right).
Figure 4. Lymphoid Lineage Assessment. Shown is the lymphoid lineage assessment between the test and predicate methods. 100% agreement was achieved in the mature lymphoid abnormal populations and 99% agreement for all lymphoid abnormal populations including both mature and immature.
Conclusion
The ClearLLab LS reagent panel showed significant agreement with the ClearLLab reagents panel in assessing the presence or absence of abnormal populations.
References
- 2006 Bethesda International Consensus recommendations on the flow cytometric immunophenotypic analysis of hematolymphoid neoplasia: medical indications. Davis BH et al. Cytometry B Clin Cytom. 2007;72 Suppl 1:S5.
- WHO Classification of Tumours of Haematopoietic and Lymphoid Tissue, 4th Edition. S. Swerdlow et al. 2008 Lyon: International Agency for Research on Cancer.
- Cancer Facts & Figures 2015. American Cancer Society
*ClearLLab LS (Lymphoid Screen) is CE-IVD marked under Regulation (EU) 2017/746. For In Vitro Diagnostic Use. The Beckman Coulter product and service marks mentioned herein are trademarks or registered trademarks of Beckman Coulter, Inc. in the United States and other countries.
