Immunophenotypic heterogeneity of multiple myeloma: influence on the biology and clinical course of the disease. Castellano-Leones (Spain) Cooperative Group for the Study of Monoclonal Gammopathies.

In 112 untreated myeloma patients we have analysed the immunophenotype of plasma cells both by immunofluorescence (IF) and immunocytochemistry (APAAP). Both techniques yielded similar results pointing to an important degree of heterogeneity in antigenic expression not only between different patients but also within the same patient. The expression of CD38 and Han-PC1 antigens (Ags) was almost constant (greater than 90% positive cases), while CD9 was detected in 66% of the cases. On the other hand, less than one third of patients were positive for CD10, CD20 and HLA-DR and generally with a weak expression (less than 30% positive plasma cells). In occasional cases plasma cells were weakly positive for the myelomonocytic markers CD13 (9%), CD15 (25%) and CD14 (6%). The possibility that this heterogeneity might be the result of different stages of differentiation of the neoplastic clone is suggested both by the positive correlation in the expression of some of these antigens (CD10, CD9, CD20, HLA-DR) and by the relationship between CD10 and myeloid antigens with immature plasma cell morphology. Finally, the cALLA antigen does not seem to be of significant value in predicting survival. Moreover, none of the other markers explored showed a clear influence in the course of the disease, although the tendency towards a lower survival found for the CD20+ cases as well as the association of the expression of some antigens and advanced clinical stage, may warrant further studies in a larger series of patients.

Combination of interferon and dexamethasone in refractory multiple myeloma.

The present pilot study was designed to analyse the efficacy and toxicity of the association of interferon (IFN) and dexamethasone (Dx) in 32 resistant and relapsed myeloma patients. Among the evaluable cases, 15 (68 per cent) responded to treatment (32 per cent achieved an objective response--OR--and 36 per cent a partial response--PR--), the 'remission' status lasting for more than one year in six of them. Moreover, four out of the seven OR patients showed a reduction in B.M. plasma cells to less than 5 per cent. Five out of 11 patients that were previously refractory to VBAD, that includes high dose dexamethasone (Dx), responded to IFN-Dx. The protocol was generally well tolerated with only four patients discontinuing therapy due to adverse effects. The present results show that the combination IFN + Dx is a promising therapeutic approach for patients with refractory myeloma.

[Utility of the examination of plasma-cell morphology in the study of multiple myeloma]. / Utilidad del examen de la morfología de la célula plasmática en el estudio del mieloma múltiple.

PURPOSE: To assess the classification of Greipp et al in a group of multiple myeloma (MM) patients, in an attempt to correlate the morphological patterns with the clinico-biological features of the disease. MATERIAL AND METHODS: Bone marrow aspirates from 135 patients with multiple myeloma were examined by two different observers. RESULTS: Full accordance existed in 122 cases (90%). The four morphological MM subgroup distribution was: mature, 38%; intermediate, 30%; immature, 18%, and plasmoblastic, 14%. The analysis of the M component types with regard to morphology showed increased IgA cases within the intermediate (40%) and immature (48%) MM (p = 0.01), and Bence-Jones cases within the plasmoblastic MM (32%). On the contrary, no differences were found with regard to the clinical stage, although none of the plasmoblastic MM was in stage I. The incidence of renal insufficiency and of high bone-marrow infiltration progressively increased from mature to plasmoblastic MM, the difference between the extreme morphological groups being significant. The incidence of hypercalcaemia and lower paraprotein rates was higher in plasmoblastic myeloma, with significant difference with respect to mature myeloma (p = 0.05). The median survival was longer in intermediate (27.8 months) and mature (22.5 months) myelomas than in plasmoblastic (17.9 months) and immature (13.6 months) myelomas. After grouping the mature forms (intermediate plus mature) and the immature ones (plasmoblastic plus immature) the survival differences approached statistical significance (p = 0.07). CONCLUSIONS: This study suggests that the morphological examination of plasma cells should be included in the prognostic criteria of multiple myeloma.

Increased expression of natural-killer-associated and activation antigens in multiple myeloma.

The expression of both natural-killer (NK)-associated and activation antigens was studied by flow cytometry in the peripheral blood of 47 untreated multiple myeloma (MM) patients. A significant increase in both absolute and relative numbers of CD57 positive cells as well as in the proportion of CD16 and CD11b cells was observed in patients with MM, specially in those in early stages of the disease (clinical stages I and II), suggesting a possible surveillance mechanism in response to an emerging malignant clone. Additional double stainings showed that strong CD16+ NK cells coexpress the CD56, CD11b, and CD2 antigens, while they lacked CD3, CD5, and WT31 antigens. Moreover, the previously reported increase in CD8 cells present in MM would be mainly due to a subset of CD8 cells that coexpress the CD57 Ags. The expression of activation antigens, especially CD38, was increased in peripheral blood lymphocytes of MM patients, the differences reaching statistical significance both in absolute and relative numbers in those cases with high numbers of CD16 NK cells and thus suggesting that these cells are functionally activated. These results reveal the existence of an increase in NK and activated cells in the peripheral blood of myeloma patients that may reflect a host's immunological mechanism in an attempt to modulate tumor cell growth.

Lymphoid subsets and prognostic factors in multiple myeloma. Cooperative Group for the Study of Monoclonal Gammopathies.

In a uniform series of 170 untreated myeloma patients (MM) we investigated the distribution of T cell subsets in peripheral blood (PB) and their relationship with the most relevant disease characteristics, including survival. CD4 cells were significantly decreased both in percentage and absolute numbers (P less than 0.0001). On the other hand, the CD8 cells only showed a slight increase in relative numbers. Upon correlating the abnormalities in the distribution of T cells with other clinical and biological disease characteristics the most remarkable correlation was with survival. A low number of CD4 cells (less than 700 x 10(6)/l) was associated with both an advanced clinical stage and a shorter survival (20 v. 43 months, P = 0.01). Moreover, a significant correlation also exists between the decrease in CD4 cells and both high beta 2-microglobulin (beta 2M) levels and anaemia. On the other hand, no relationship was found with the type of M-component nor with the plasma cell phenotype. Finally multivariate analysis showed that the number of CD4 cells add independent prognostic information to other well-established tests for the assessment of disease outcome in patients with multiple myeloma.