[Morphologic/immunologic phenotype discrepancy in B-cell acute lymphoblastic leukemia].
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Biomedical subjects
Publications and source records attributed to A Orfao.
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The value of the immunophenotypical subtypes and individual markers was compared with classical parameters in the prognosis of 150 patients with acute lymphoblastic leukemia (ALL). Regarding the immunophenotype, common-ALL had a better prognosis than T-ALL in the children's group. However, in adults the situation was different since both null and T-ALL patients had longer survival rates than the common pre-B group. Moreover, several individual markers add interesting prognostic information, either in ALL as a whole group or within the different immunophenotypes. Thus, the expression of CD10 and TdT had a significantly favourable influence in the outcome of the whole series of patients; within the T-ALL, those cases positive for CD10 also had a longer median survival (33 versus 17 months). In addition, in the common ALL patients group the expression of a relatively mature B marker--CD20--appeared to have a favourable prognosis (27 versus 13 months). Other non lineage specific markers, such as CD9 and CD38 did not seem to influence survival. Regarding the more conventional parameters, our data suggest that the classical age prognostic classification in children (less than 15 years) and adults can be improved using two cut-off points at 11 and 35 years. Moreover, the multivariate analysis showed that this variable, together with FAB morphology and WBC counts were the best combination of parameters for predicting survival. The present study shows that although the immunophenotype helps us in understanding the biological heterogeneity of ALL, having also prognostic implications, there are other clinical and hematological features that yield stronger prognostic information.
Biological markers capable of predicting the clinical outcome of antithyroid drug therapy could be clinically useful in selecting the modality of treatment for Graves' disease, but at present they are unavailable. In the present study we prospectively explore the value of 22 different peripheral blood T, B and NK lymphocyte subsets to predict remission and relapse in a group of 42 Graves' disease patients. Eighteen patients were studied at diagnosis, before treatment, and 24 during antithyroid drug therapy. All cases were followed-up for at least one year after finishing an 18 month cycle of methimazole therapy. The combination of flow cytometry and 3- color immunofluorescence did not reveal significant differences in the distribution of the major peripheral blood T, B and NK cell subsets between the relapsed patients and those in remission, both in the groups studied at diagnosis and in those analyzed during the cycle of antithyroid drug therapy. In our search for a prognostic marker for relapse prediction we found that some lymphoid subpopulations such as total B cells, total NK and NK CD8+ cells showed high sensitivity (88-100%). In turn, other subsets such as TCD8+, total T and B cells expressing the CD25 antigen displayed high specificity (77-88%).
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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.
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The techniques of flow cytometry are becoming more and more important for the clinical hematology laboratory. No longer a novelty confined to a few specialized institutions as it was 10 years ago, flow cytometry has blossomed into a mature discipline. The methodology is well-known, the mechanical apparatus is readily available, and the role it plays in clinical hematology is increasingly appreciated. The burgeoning number of scientific articles devoted to this topic attests to the interest it has aroused as a tool for both medical research and patient care. In fact, more than a thousand such papers are now published each year and it would be impossible to deal with all the methodologies and applications of FCM currently utilized or under development. Throughout this paper four relevant hematologic fields are briefly discussed, in which FCM appears to be of great help at present: the immunophenotyping of leukemias and lymphomas, the measurement of proliferative activity and DNA ploidy in hematological malignancies, the detection of drug resistant leukemic cells and the use of FCM in the study of platelets.
Surface immunoglobulins (sIg) are traditionally considered to be absent in plasma cells (PC). However, it has recently been reported that up to one third of myeloma patients are positive for surface immunoglobulins. Nevertheless, this observation has not been confirmed in other studies. In order to assess whether or not sIg are really expressed by myelomatous PC and to exclude possible staining of either cytophilic or cytoplasmic Igs, simultaneous experiments were carried out with i) incubation at 37 degrees C, ii) blocking with non-conjugated anti-Ig light chains, and iii) cytoplasmic staining after cell membrane fixation and permeabilization. Triple staining for CD38/kappa/lambda was used in all cases and the staining intensity was quantitated in MESF (molecule equivalents of soluble fluorochrome). In addition, 20 B-CLL cases and 10 healthy donors were used as reference controls. Our study shows that 7 out the 20 patients (35%) analyzed expressed sIg and that the surface staining was specific.
BACKGROUND AND OBJECTIVE: In the present study we analyzed the incidence of nulisomy Y by fluorescence in situ hybridization in a group of 24 males diagnosed with myelodysplastic syndromes (MDS). We explored the relationship between this chromosome abnormality and other clinical and biological disease characteristics. METHODS: Loss of chromosome Y was present in 7 out of the 24 males analyzed (29%); the number of cells carrying this chromosome aberration ranged between 19% and 90%. From the clinicobiological point of view, the group of patients with nulisomy Y showed a higher incidence of RA and RAS FAB subtypes (p = 0.04), a lower WBC count (p = 0.04), a lower proportion of blast cells both in PB (p = 0.009) and BM (p = 0.06) associated with a decreased myeloid/erythroid ratio (p = 0.01). RESULTS: No clear association was detected between loss of chromosome Y and other numerical chromosome abnormalities involving chromosomes 7 and 8. In contrast, 2 out of the 7 cases with loss of chromosome Y also displayed monosomy 1 by FISH. However, the use of appropriate dual stainings showed that these two abnormalities were present in different cell populations (that is, they never coexisted in the same cell population), which supports the notion of the existence of clonal heterogeneity in MDS patients. INTERPRETATION AND CONCLUSIONS: From the prognostic point of view, MDS patients with loss of chromosome Y displayed a higher survival rate, although these differences did not reach statistical significance.
On October 16, 1996, the first Latinamerican Consensus Conference for the Immunophenotyping of Leukemia took place in the City of Puebla, Mexico, with representatives from ten countries of the region, and two external consultants. This document summarizes the major conclusions where scientific consensus was achieved.