Search PubMed⌕ Search

Biomedical subjects

M J Moro

Publications and source records attributed to M J Moro.

49 records · Page 3Linked to original sources

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.

ADP-ribosyl Cyclase↗

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.

Age Factors↗

[Utility of the examination of plasma-cell morphology in the study of multiple myeloma].

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.

Aged↗

[Clinico-hematological characteristics of acute transformation of chronic myeloproliferative syndromes].

BACKGROUND: The aim of the present study was to analyze the blastic transformation occurring during chronic myeloproliferative diseases (CMPD) and to establish the differences between them. METHODS: The clinical and hematological characteristics of 54 patients in blastic crisis (BC) of a CMPD were analyzed: 40 chronic myelogenous leukemias (CML), 9 idiopathic myelofibroses (IMF), 4 polycythemia vera (PV), and one essential thrombocythemia (ET). The results were analyzed by the BMDP statistical program. RESULTS: The BC of CML appeared in younger patients (p less than 0.05). Only in this group did some patients achieve complete remission. Moreover, in this BC a greater incidence of visceromegalies and leukocytoses were observed. The BC of the IMF patients led to marked anemia (p less than 0.01) and bone marrow infiltration (p less than 0.05); these leukemias were more frequent in males and began with lymphadenopathies and visceromegalies. The transformations of PV were preceded by a longer chronic phase and had a lower incidence of visceromegalies and a nearly normal hemoglobin count value. The patient with acute leukemia secondary to ET did not display visceromegalies but did have anemia, leukopenia and a normal platelet count. None of the four groups responded to therapy, and their survival was short. CONCLUSIONS: Blast transformations of different myeloproliferative disorders have their own idiosynchratic clinical and hematological characteristics, some of these may be related to the chronic phase of disease.

Age Factors↗

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.

Aged↗

A randomized multicentric study comparing alternating combination chemotherapy (VCMP/VBAP) and melphalan-prednisone in multiple myeloma.

Between January 1985 and December 1988, 386 patients with multiple myeloma were randomized to receive either MP or combination chemotherapy based on alternating cycles of VCMP and VBAP. The major prognostic parameters did not differ significantly between both treatment groups. A significantly higher proportion of objective responses was observed with combination chemotherapy as compared to MP (47.8 vs 32.2, P = 0.01). The median survival for all patients was 33.5 months. So far no significant differences were found when comparing the survival curves from both groups of patients. However, the median survival of MP-treated patients is 26.8 months, whereas the median survival of patients receiving VCMP/VBAP has not yet been reached. The definitive analysis must await the evaluation of all patients entered into the study and a longer follow-up time.

Antineoplastic Combined Chemotherapy Protocols↗

Leukemias with megakaryoblastic involvement: clinical, hematologic, and immunologic characteristics.

The clinical, hematologic, and phenotypic features of 28 patients with acute leukemia with megakaryocytic involvement (AMKL) were analyzed. The prevalence of this type of leukemia in the entire series was 11.6%, with a higher incidence among patients with acute transformation of a previous myeloproliferative disorder (MPD) (24%) than among the transformed myelodysplastic syndrome (13%) patients. The incidence in the "de novo" ANLL was 8% and 16% among secondary leukemias. The presence of bone marrow fibrosis together with low WBC and normal or increased platelet counts despite a severe anemia are the most relevant features in these patients who otherwise displayed an apparently poor prognosis. Megakaryoblasts were morphologically recognized more frequently in the acute transformations of MPD than in de novo ANLL. Only two cases were considered pure AMKL, and in the remaining 26 patients, megakaryoblasts coexisted with other granulomonocytic and/or erythroid populations. Antiglycoprotein IIIa (anti-GPIIIa) (C17) and anti-GPIIb/IIIa (CDw41-, J15-) antibodies are probably the best markers for AMKL, although the monoclonal antibody against GPIX (FMC25) was also positive in a majority of cases but in a lower percentage of cells. On the other hand, megakaryoblasts were generally negative for granulocytic or monocytic markers (CD13, CD14, CD15); the expression of HLA-DR antigens in these cells was variable. Our present results indicate that megakaryoblastic involvement is more common than previously recognized. This is true not only in acute transformed leukemias but also in de novo ANLL. Although the diagnosis of these cases should be based on megakaryocytic markers, it is often possible to suspect a diagnosis according to certain clinical and hematologic features.

Adult↗

Interaction between clonal plasma cells and the immune system in plasma cell dyscrasias.

The term "monoclonal gammopathy" (MG) includes a group of clonal plasma cell disorders, which show heterogeneous clinical behavior. While multiple myeloma (MM) and plasma cell leukemia (PCL) are incurable malignant diseases, most patients with MG of undetermined significance (MGUS) show an indolent/benign clinical course. Evidence has accumulated which supports the role of the bone marrow microenvironment in MG. Accordingly, the survival, drug-resistance and proliferation of MM cells have been shown to be largely dependent on a supportive microenvironment. Among the different environment-associated parameters, those related to the status/activity of the immune system are particularly relevant. This review focuses on the different ways clonal plasma cells (PC) interact with the immune system in different models of MG, to characterize crucial events in the development and progression of MG. These advances may support the design of novel therapeutic approaches in patients with MG.

Bone Marrow↗