IDENTIFICATION OF PROGNOSTIC FACTORS FOR MALIGNANT TRANSFORMATION IN PERSONS WITH MONOCLONAL GAMMOPATHY OF UNDETERMINED SIGNIFICANCE OBSERVED IN THE CZECH REPUBLIC

Sborník

Background. Monoclonal gammopathy of unknown significance (MGUS) is a potentially malignant condition associated with a cumulative probability of progression into one of the malignant forms of monoclonal gammopathy approximately 1% per year (Kyle et al., New Engl J Med 2002). Aims. The aims of this study were to verify the validity of already known risk factors separating benign and malignant MGUS using Register of Monoclonal Gammopathy (RMG) of Czech Myeloma Group. Methods. Before inclusion to RMG all persons signed informed consent. Total of, 1448 persons with MGUS were enrolled to the RMG in the Czech Republic retrospectively and prospectively, from May 2007 to November 2011. A total of 99,3% (1439/1448) persons were analyzed. The median follow up was 5 years (range 1.0 to 18.0). Results. Total of 7,1% (96/1356) persons with MGUS progressed into malignant form; 75% (72/96) into multiple myeloma; 10,4% (10/96) into Waldenstrom macroglobulinemia; 5,2% (5/96) into malignant lymphoma; 2,1% (2/96) into primary amyloidosis; 7,3% (7/96) into other types of malignancy with the median time to transformation 3 years (range 0-15 years). Variables associated with significantly higher risk of transformation were as follows: serum paraprotein levels >15 g/l (25,8% vs. 4,48%; p< 0.001), bone marrow plasma cells infiltration >5% levels (22,3% vs. 5,4%; p< 0.001), abnormal κ/λ index < 0,26 or > 1,65 (75,6% vs. 42,7%; p< 0.001), serum baseline lactate dehydrogenase levels >3,75 ukat/l, (7,82% vs. 4,62%; p= 0.016) and serum baseline hemoglobin levels <120 g/l (7,82% vs. 4,62%; p= 0.007). In contrast to stratification system published by Rajkumar et al.(Blood 2005), we did not find any correlation between Ig isotypes (non IgG vs. IgG) (32,6% vs. 29,5%; p= 0.523), however high-risk subgroup (presence of all three abnormal risk factors) belonged to a group with a relative risk (Hazard Ratio; HR) almost 18 times higher than normal (17.54; CI (5.78; 53.22); p<0,001) when Cox model was used to identify possible predictors of malignant transformation. High HR (4.18, CI (2.59, 6.74), p <0.001) also had a number of plasma cells greater than 5% levels, serum paraprotein levels >15g /l (HR 3.64, CI (2.39, 5.54) p <0, 001) and pathological values of the κ/λ index HR was 2.9 (2.90 (1.47, 5.75), p = 0.002). Persons in the lowest risk group had 5-year survival without malignant transformation in 96,7% of cases with an annual risk of transformation under 1%, while the highest risk group in 55,6% of cases with and annual risk of transformation about 8-9%. Conclusions. Our results confirm the validity of the known risk factors, except type of Ig for prediction of MGUS transformation into malignancy. Currently, we can well define the group with the lowest risk with an annual risk of transformation < 1%. Further optimization of the currently used model of stratification is required mainly for other than low risk groups. At this point, our data form one of the largest set of analyzed subjects with MGUS in the world; however, a certain limitation is a short median follow-up. Funding. Supported by grants: MSM0021622434 and GAP304/10/1395

Haematologica, 2012; 97(s1):  344