Assessing Minimal Disease in Plasma Cell Neoplasms: A Comparison between Multicolor Flow Cytometry and Immunohistochemistry
David P Ng, Cynthia S Liang, Tian Tian, Cameron Yin, Ken H Young, Jeffery L Jorgensen, Daniela Hoehn, Rachel Sargent, Roberto N Miranda, Hesham M Amin, James You, Ellen Schlette, Pei Lin. The University of Texas MD Anderson Cancer Center, Houston, TX; Dartmouth Hitchcock Medical Center, Lebanon, NH
Background: Assessment of minimal disease (MRD) in plasma cell (PC) neoplasms has important therapeutic and prognostic implications. Currently, there are no systematic studies comparing the detection sensitivity of multicolor flow cytometry (FC) versus immunohistochemical (IHC) staining performed concomitantly on bone marrow aspirate and biopsy samples.
Design: We evaluated consecutive bone marrow samples of 144 patients that were analyzed by FC and IHC or in situ hybridization (ISH) for monotypic PCs between June and September of 2011. We included those that had ≤ 5% PCs from bone marrow differential count (n=112) in this study. PCs were analyzed by a 6-color FC assay using a panel of monoclonal antibodies against CD45, CD38, CD138, CD19, CD20, CD28, CD56, CD117, cytoplasmic immunoglobulin κ and λ, collecting 100,000 total events. CD138 was used to evaluate the degree and pattern of involvement and κ and λ were used to assess light chain expression by IHC or ISH. Serum free light chain ratios (sFLC) of a subset of patients was also reviewed. The data was analyzed using Fisher's exact test and Student's t-test.
Results: Of the 112 cases, monotypic PCs were detected in 68 (61%) and 53(47%) cases by FC and IHC/ISH, respectively (p=0.060). Seventeen cases had discordant results: FC+/IHC- in 16 and FC-/IHC+ in 1 case. In the FC-/IHC+ case, a single small cluster of PCs with lambda excess was identified. In the 16 FC+/IHC- cases, the infiltrate of PCs was interstitial and scattered. Also among these 16 cases, the sFLC ratio was abnormal in 7 and equivocal in 6 of 13 cases assessed. Assuming a combined result of FC and IHC/ISH as a gold standard, FC was 98.5% sensitive whereas IHC/ISH was 76.8% sensitive (P<0.001). The average percentage of PCs was 2.0% and 2.63% in the aspirate of the FC+/IHC- discordant cases and the FC+/IHC+ concordant cases, respectively (Not Significant).
Conclusions: FC is more sensitive in detecting aberrant and monotypic PCs. While the false negative rate is <1%, due to sampling issues, FC appears to be an effective method for the detection of MRD, and the addition of CD138 by IHC can help evaluate extend and patterns of infiltration without a need of further assessment of light chain expression by IHC/ISH.
Wednesday, March 21, 2012 1:00 PM
Poster Session VI # 226, Wednesday Afternoon