FLOW CYTOMETRY AS A PREDICTIVE TOOL FOR TRANSFORMATION OF MGUS INTO MM

Sborník

Background. Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant state with possibility of the transformation into multiple myeloma (MM). Traditional prognostic parameters have limited sensitivity and specificity to predict transformation within 3 years from time of diagnosis. MGUS is characterised by presence of mixture of normal CD19+ and abnormal CD19- plasma cells (PCs). Disappearance of CD19+ PCs should correlate with transformation, but there are other markers exist which could be useful in prediction of transformation MGUS into MM. Aims. Flow cytometry analysis of surface antigens and their comparison with standard prognostic factors to predict possibility of transformation MGUS into MM. Methods. Analysis of 150 untreated MGUS cases in time of diagnosis was done. Number of CD19+ B cells and CD38+CD138+ PCs was analysed in whole bone marrow. Expression of CD19, CD56, CD20, CD27, CD28 and CD117 on PCs was analysed by flow cytometry. Parameter CD19- PCs is equivalent to abnormal PCs. Flow cytometry results were compared with standard prognostic factors. Results. Transformation of MGUS into MM was found only in 9 subjects. These have statistically decreased number of B cell [7.0% (0.0-23.7) vs. 13.3% (1.2-68.4); p<0.02], increased number of PCs [1.0% (0.2-8.8) vs. 0.4% (0.0-4.2); p<0.01] and decreased number of normal CD19+ PC [3.8% (0.9-33.4) vs. 25.9% (0.2-87.2); p<0.002] when compared to subjects without transformation. There were found non-significant decrease of CD27 and increase of CD56 expression on PCs in transformed group. Surprisingly, there was found almost IgG isotype of clonal immunoglobulin (MIG) in 93.5% (29/32) subjects with CD28+ PCs. Significantly higher MIG concentration (>15g/l) was found only in cases with CD19+ PC ≤5% (p=0.001), but abnormal FLC index was found already when CD19+ PC <20% (p=0,017). Subjects with CD19+ PC ≤5% were more frequently presented in high medium risk group when compared to subjects with CD19+ PC >5% presented more frequently in low medium risk group (p=0.009). When analysed connection between parameter “CD19+ PC ≤5%” and progression into MM, this parameter was able to predict progression with 55.6% sensitivity and 91.2% specificity (p=0.019). Conclusions. Flow cytometry in analysis of MGUS cases seems to be helpful approach. The most powerful factor is presence and/or loss of CD19 on PCs. Decrease of relative count of CD19+ PC under 5% (from whole PC population) can predict possibility of transformation into MM what is in concordance with previously published results. Funding. Supported by MSM0021622434, IGA NT12425 and GACR P304/10/1395 grants

 Haematologica, 2012; 97(s1):  354