Biomedical subjects

J A Portero

Publications and source records attributed to J A Portero.

14 recordsLinked to original sources

PubMed2004

Proliferative activity of plasma cells is the most relevant prognostic factor in elderly multiple myeloma patients.

Although multiple myeloma (MM) is predominantly a disease of the elderly, few studies have focused on the identification of prognostic factors in this group of patients. Four hundred twenty five MM patients >65 years were uniformly treated with chemotherapy (MP or VCMP/VBAD). Multivariate analysis identified 4 factors with independent unfavorable prognostic influence: high percentage of S-phase bone marrow plasma cells (>2.5%); elevated beta(2) microglobulin (B2M) (>4 mg/L); age >80 years old; and LDH serum levels (above normal limit). The S-phase value was the most powerful independent prognostic factor to discriminate subgroups of patients with different prognosis. Thus, 3 main risk categories could be identified according to S-phase values: </=1%, 1-3% and >3%, with median survivals of 34, 22 and 12 months, respectively (p < 0.0001). Our study also proved the value for elderly patients of the recently developed International Score System (ISS) based on B2M and albumin. Furthermore, the number of S-phase cells helped to subdivide the ISS III Group identifying a subset of patients with very poor prognosis defined by an additional high S-phase, who displayed a median survival of only 8 months. These results demonstrate that elderly patients can be accurately classified according to prognosis, which may be particularly valuable when comparing the efficacy of new treatment strategies. Moreover, our results underline the high prognostic value of proliferative activity of PC, a parameter that should be considered in routine laboratory investigations of MM.

Age Factors↗

PubMed2001

Fluorescence in situ hybridization study of TEL/AML1 fusion and other abnormalities involving TEL and AML1 genes. Correlation with cytogenetic findings and prognostic value in children with acute lymphocytic leukemia.

BACKGROUND AND OBJECTIVES: The TEL/AML1 fusion is the most common genetic abnormality found in childhood acute lymphoblastic leukemias (ALL). Although it is very difficult to identify by conventional cytogenetic techniques it can be readily detected using fluorescence in situ hybridization (FISH). We carried out cytogenetic and FISH studies on 42 children with ALL in order to know the frequency of this translocation in our population, the incidence of TEL and/or AML1 gene alterations, and their correlation with clinical evolution and prognosis. In addition, we performed reverse transcription polymerase chain reaction (RT-PCR) in some cases, confirming the feasibility of FISH techniques in the detection of this translocation. DESIGN AND METHODS: Bone marrow samples were obtained from 42 childhood ALL patients. The copy number of AML1 and TEL genes were studied using fluorescent in situ hybridization with a dual color DNA probe specific for the AML1 and TEL genes. RESULTS: We found a frequency of TEL/AML1 fusion of 17% in our sample. Double TEL/AML1 fusion, lack of TEL signal and extra AML1 signals were frequent additional FISH abnormalities. Duplication of a chromosomal complement, deletion of chromosome 12p arm, and polysomies of chromosome 21 are plausible explanations for these additional FISH findings. However, a relatively high proportion of our cases (9.5%) presented specific amplification of AML1. A statistically significant difference in prognosis was found between patients with and without these additional AML1 or TEL FISH alterations (p<0.02), which could be related to the presence of specific karyotypes. INTERPRETATIONS AND CONCLUSIONS: The frequency of TEL/AML1 fusion is similar to that found in other populations (17%). We found that FISH analysis of AML and TEL is related to the evolution of the disease. The absence of alterations in these genes revealed by FISH could be indicative of bad prognosis, while the presence of alterations is related to a good evolution. Our results suggest that interphase FISH analysis to search for alterations in AML and TEL genes could be extremely useful for complementing cytogenetic studies and for providing additional information about the possible outcome of the disease in patients with ALL.

Adolescent↗

PubMed1997

[High cardiac output in myeloma patients. Its prevalence and clinical characteristics. The Castile-León Cooperative Group for the Study of Monoclonal Gammapathies].

BACKGROUND: The study determines the prevalence of high cardiac output status in patients with multiple myeloma (MM) and its relationship with the more significant clinical and biological characteristics of the disease. PATIENTS AND METHODS: Cardiac output was determined in 28 patients with multiple myeloma by pulsed Doppler echocardiography. Patients with any other identifiable cause of high cardiac output were excluded. Mean age was 70 +/- 8 SD years (53-84). A stepwise regression with the cardiac output as dependent variable and age, performance status (ECOG), clinical stage (Durie and Salmon), scale of bone lesions, serum calcium, serum creatine, bone involvement (percentage), and M protein quantity as independent variables showed the following results. RESULTS: A high cardiac output state, defined as a cardiac index higher than 4.6 l/min/m2 was present in five patients (17.8%), four of them with severe bone involvement. Two patients developed heart failure. The stepwise regression revealed the scale of bone lesions was the unique variable associated with the risk of developing a high cardiac output status. CONCLUSIONS: A high cardiac output status may be fairly common in patients with multiple myeloma. The syndrome is associated with severe bone involvement, being the scale of bone lesions the only risk factor for this complication.

Aged↗

PubMed1997

Detection of trisomy 8 using conventional cytogenetic techniques and interphase FISH analysis in 34 myeloid disorders: a comparative study.

Trisomy for chromosome 8 is one of the most common chromosome abnormalities detected in myeloid disorders. However, and despite its great incidence, its biologic significance remains poorly understood. Recently, some reports have shown the existence of masked trisomy 8 in myeloid disorders. To try to detect occult trisomy 8, we performed a study in which 34 myeloid disorders with apparent normal karyotypes using conventional cytogenetic techniques were analyzed using fluorescence in situ hybridization (FISH) analysis. Masked trisomy 8 was not detected in any of the 34 cases studied. This suggests that trisomy 8 may be a rare event in myeloid disorders in which an optimal conventional cytogenetic analysis has been performed. The acquisition of trisomy 8 either in early neoplastic stages in some cases or in late neoplastic stages in others and the absence of masked trisomy 8 suggest that this chromosome alteration may not be essential to the development of myeloid disorders.

Bone Marrow↗

PubMed1996

Analysis of natural killer-associated antigens in peripheral blood and bone marrow of multiple myeloma patients and prognostic implications.

The aim of this study was to analyse the expression of NK-associated antigens in both peripheral blood and bone marrow lymphocytes from a large series of newly diagnosed multiple myeloma patients. 112 patients with untreated multiple myeloma (MM) were included in the study. 36 sex- and age-matched healthy volunteers were used as controls for peripheral blood (PB) studies and 14 for the bone marrow (BM) studies. Simultaneous stainings with the CD3/CD56, CD2/CD16 and CD8/CD57 monoclonal antibodies were systematically performed in PB and CD3/CD56 and CD2/CD16 in BM in order to analyse their relationship with the clinical and biological characteristics of the disease and survival. The expression of NK-associated antigens (CD56, CD16 and CD57) assessed within the lymphoid gate, was significantly increased (P < 0.001) in the PB of MM patients both in relative and absolute numbers. In the BM a significant increase in the percentage of CD56+ lymphocytes (P < 0.001) was also observed; in contrast, the proportion of CD16+ cells did not differ significantly from that of normal BM samples. The number of CD56+CD3- lymphocytes increased significantly within high-risk patients (869 +/- 671) as compared to intermediate (388 +/- 212) and low-risk patients (274 +/- 199) (P = 0.04). Moreover, patients with high values of CD56+CD3- lymphocytes showed a statistically significant association with several adverse prognostic factors including anaemia, hypoalbuminaemia, renal failure, high beta 2M, DNA diploidy and high S-phase plasma cells. In addition, patients with higher absolute numbers of PB CD56+CD3-lymphocytes displayed a poorer prognosis, whereas patients with higher values of CD57+CD8- cells had a better outcome.

Adult↗

PubMed1993

[Detection of translocation (15;17) using cytogenetic and molecular techniques. Comparative study in 15 patients with acute promyelocytic leukemia].

PURPOSES: To analyze the reproducibility to detect the t (15; 17) with molecular and cytogenetic techniques. PATIENTS AND METHODS: Fifteen cases of acute promyelocytic leukaemia were studied by means of cytogenetic techniques (GTG banding) and molecular ones (K/S probe and HindIII, EcoRI and BamHI restriction enzymes). RESULTS: The t (15; 17) was detected with cytogenetic techniques in 60% cases and with molecular ones in 33% cases. Using both (cytogenetic and molecular) techniques the translocation was detected in 73% cases. CONCLUSIONS: The use of both techniques may be very useful in order to get a better diagnostic and a closer control of the patient's clinical evolution.

Chromosome Banding↗

PubMed1992

[Prognostic effect of beta 2-microglobulin in multiple myeloma].

BACKGROUND: The aim of the present study was to compare the prognostic influence of beta 2-microglobulin (B2M) corrected according to renal function versus the uncorrected form and relate these values with other characteristics of the disease in a series of patients with multiple myeloma (MM). METHODS: The serum levels of B2M were determined by the radioimmunoassay method (RIA) in 107 patients with newly diagnosed MM and the prognostic influence of B2M was statistically evaluated with univariant and multivariant analysis. RESULTS: The mean value of B2M obtained in patients with MM was 7.8 +/- 8.0 micrograms/ml, with a median of 5 micrograms/ml. Ninety percent of the patients studied presented serum values of B2M higher than the normal limit. The value of B2M corresponding to the median of the series (5 micrograms/ml) separated two groups of patients with different survival (48 vs 19 months) (p = 0.0001). Similarly, the most discriminative value of corrected B2M in agreement with creatinine (2.5 micrograms/ml) permitted the differentiation of two groups of patients although the differences in survival were less significant (36 vs 26 months, p = 0.03) demonstrating its lesser influence as a prognostic factor with respect to the uncorrected B2M. In contrast, a significant association was observed between high values of B2M and Bence Jones myeloma, clinical stage III, anemia, renal failure and intense involvement of the general state. Multivariant analysis demonstrated that B2M plays a greater prognostic role when used as a discrete rather than a continuous variable and that together with the degree of involvement of the general state, serum albumin and the proportion of plasma cells in the bone marrow, they make up the best set of variables for the prediction of prognosis in patients with MM. CONCLUSIONS: Beta 2-microglobulin is one of the most important independent prognostic factors in multiple myeloma with its prognostic value being greatest when used uncorrected according to the values of creatinine.

Bence Jones Protein↗

PubMed1992

[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↗

PubMed1986

TdT activity in acute myeloid leukemias defined by monoclonal antibodies.

Blast cells from eight out of 71 patients diagnosed with acute myeloid leukemia (AML) by morphological, cytochemical, and immunological criteria showed TdT activity. Their distribution according to the FAB classification was one M1, one M2, one M4, two M5a, one M5b, one M6, and one undifferentiated case. The TdT+ AML cases did not show major clinical and hematological differences when compared with the classical TdT- AML patients. Other phenotypical aberrations in the expression of membrane antigens, apart from the presence of nuclear TdT, were not observed in these TdT+ cases after study with a large panel of monoclonal antibodies. A higher incidence of TdT+ cases was found among the monocytic variants of AML (M4 and M5)--four cases--than in the granulocytic variants (M1, M2, and M3)--2 cases. These TdT+ cases should be distinguished from mixed leukemias by double labeling techniques, assessing in the TdT+ AML the coexpression of TdT and myeloid markers in individual cells as shown in four of our cases.

Adult↗

PubMed1985