No abstract

The aim of this prospective, long-term study was to define the flow cytometric characteristics of plasma cell CD56 expression as well as determine the clinical characteristics of 204 multiple myeloma (MM) patients and 26 plasma cell leukemia (PCL) patients with regard to CD56 expression. CD56 expression intensity was determined by measurement of antigen molecules on the cell defined as Antibodies Bound per Cell (ABC) and calculation of Relative Fluorescence Intensity (RFI). CD56 expression was found in 66% of MM and 54% of PCL cases. The RFI values for individual MM patients ranged from 7.6 to 27.4 while ABC values on MM plasma cells from 2255 to 58469. There was a correlation between the proportion of all bone marrow CD38(++)/CD138(+) cells with CD56 expression and ABC and RFI indices. With regard to CD56 expression positive patients, the CD56(-) MM patients presented lower frequency of osteolysis (p = 0.01). The median survival was 48 months in CD56(+) patients and 43 months (p = 0.84) in CD56(-) cases. In conclusion, CD56 expression carries no distinct adverse prognosis and the lack of CD56 expression does not define a unique clinicopathological or prognostic entity in MM. A remarkable heterogeneity of CD56 expression intensity in CD56(+) patients imposes the necessity of determining CD56 expression intensity in candidates to antibody-based therapy.

The surface expression of CD117 antigen (c-kit) on plasma cells from 158 multiple myeloma (MM), 12 plasma cell leukemia (PCL), 7 MGUS, 7 IgM lymphoplasmacytic lymphoma patients and 10 healthy subjects has been analyzed by flow cytometry using triple staining with the monoclonal antibodies CD138, CD117 and CD38. The antigen expression intensity was calculated as relative fluorescence intensity (RFI) and for direct quantitative analysis the QuantiBRITE test (Becton Dickinson) was applied. Antibody bounding capacity (ABC) was calculated using QuantiCALC software. CD117 antigen was present in 49/158 MM, 5/12 PCL and 5/7 MGUS patients. The RFI values ranged from 0.2 to 20.2 in particular MM patients (mean: 11.0+/-5.3; median 11.5) while the number of CD117 binding sites (ABC) on MM plasma cells ranged from 637 to 6217 (mean: 3029+/-1568; median 2946) (r=0.8328). In responsive to chemotherapy c-kit positive MM patients the percentage of CD117+ plasma cells in the bone marrow decreased significantly while in c-kit negative MM patients the percentage of CD117+ cells in bone marrow did not change and remained in the normal limits. When comparing the clinical and biological disease characteristics (monoclonal protein isotype, albumin, beta2-microglobulin, lactate dehydrogenase, stage of disease, response to chemotherapy, survival time) of c-kit positive and c-kit negative cases, no significant differences were found. In CD117 positive PCL cases expression of CD117 was detected in bone marrow plasma cells as well as in peripheral blood plasma cells. Normal plasma cells and those in IgM lymphoplasmacytic lymphoma did not show reactivity for the CD117 antigen. We conclude that it may be rationale to consider usefulness of therapy with tyrosine kinase inhibitors in the management of c-kit positive plasma cell proliferations. In one third of MM and PCL patients c-kit antigen could be considered as a "tumor associated marker" and together with CD38 and CD138 it may be of value for the identification of the malignant clone in minimal residual disease as it was first suggested by Spanish authors.

Nineteen individuals are reported who represent nine familial instances of various immunopathies. Multiple myeloma was diagnosed in 10 members of five families, lanthanic (idiopathic) paraproteinemia in five members of two families and either myeloma or lanthanic paraproteinemia in four members of the remaining two families. The parent-child relationship occurred in three instances, siblings were affected in three, and first cousins in three families. Immunochemical studies revealed IgG paraprotein in nine cases; IgA in three; IgMl type in three subjects belonging to the same family; Bence-Jones protein in one case and biclonal paraproteinemia, IgGk plus IgAl in one. Three individual cases of lanthanic paraproteinemia, discovered in a prospective study of 76 relatives of subjects with immunopathies, suggest that there may be a higher frequency of immunopathies among family members than observed in the general population of comparable age. The published reports on familial paraproteinemias are reviewed.Cancer 40 families with multiple myeloma and related conditions. The results of studies performed on relatives of other patients with various paraproteinemias are included. MATERIALS AND METHODSThe data in these studies were collected over 9 years; the protein analyses were carried out at the Veterans Administration Hospital, Pittsburgh, and, in the relatives of family VII, at the Protein Study Center of The Memorial Hospital, Pawtucket, Rhode Island. In addition to the 29 relatives of families 1-111, VI and VII, a group of 82 close relatives of other patients with various immunocytic dyscrasias was included in these studies. Serum protein examinations consisted of electrophoresis on cellulose acetate membranes; immunoelectrophoresis was done by Scheidegger's micromodification method, quantitative immunoglobulin determination by the immunoplate method, 36 rheumatoid factor by latex fixation, and total serum proteins by a standard technique. Bence Jones protein in urine was evaluated by Snapper's heat test6'and by electrophoresis of concentrated urine. The monoclonal proteins were identified with commercially available monospecific antisera. TerminologyLanthanic paraproteinemia is used in this paper in preference to such expressions as "pre- 2094

In this prospective study we determined the incidence of intact/fragmented immunoglobulin and Bence Jones protein in urine immunofixation using Sebia reagents and HydrasysTM 2 apparatus and compared the results to concentrations of serum free light chains (FLC) assessed using Siemens BNTM II nephelometer and the immunoassay Freelite (Binding Site) in 289 patients with multiple myeloma at diagnosis. It was found that in one third of IgG, IgA and IgD myeloma patients, intact/fragmented immunoglobulin can be detected in urine and is connected with impaired renal function and reduced survival. Urine immunofixation detects monoclonal protein (FLC and intact/fragmented immunoglobulin) in 66-79% of IgG and IgA myeloma patients while serum FLC immunoassay detect it in 82-94% of IgG and IgA myeloma patients. However, the latter method is inadequate for detection of intact/fragmented immunoglobulin in urine. Serum FLC immunoassay and urine immunofixation are complementary methods in diagnosing and monitoring monoclonal protein in patients with myeloma.