Search PubMed⌕ Search

Biomedical subjects

D G Oscier

Publications and source records attributed to D G Oscier.

At least 73 records · Page 4Linked to original sources
PubMed1990

Prognostic subgroups in B-cell chronic lymphocytic leukemia defined by specific chromosomal abnormalities.

BACKGROUND AND METHODS: Specific chromosomal abnormalities have been shown to affect the overall survival of patients with acute leukemia, but the possibility that specific chromosomal defects may influence the course of B-cell chronic lymphocytic leukemia (CLL) is controversial. We assessed this possibility as follows: blood mononuclear cells from 433 patients with B-cell CLL in five European centers were cultured with B-cell mitogens, and banded metaphases were studied. RESULTS: Three hundred ninety-one patients could be evaluated cytogenetically, and 218 had clonal chromosomal changes. The most common abnormalities were trisomy 12 (n = 67) and structural abnormalities of chromosome 13 (n = 51; most involving the site of the retinoblastoma gene) and of chromosome 14 (n = 41). Patients with a normal karyotype had a median overall survival of more than 15 years, in contrast to 7.7 years for patients with clonal changes. Patients with single abnormalities (n = 113) did better than those with complex karyotypes (P less than 0.001). Patients with abnormalities involving chromosome 14q had poorer survival than those with aberrations of chromosome 13q (P less than 0.05). Among patients with single abnormalities, those with trisomy 12 alone had poorer survival than patients with single aberrations of chromosome 13q (P = 0.01); the latter had the same survival as those with a normal karyotype. A high percentage of cells in metaphase with chromosomal abnormalities, indicating highly proliferative leukemic cells, was associated with poor survival (P less than 0.001). Cox proportional-hazards analysis identified age, sex, the percentage of cells in metaphase with chromosomal abnormalities, and the clinical stage of the disease (Binet classification system) as independent prognostic variables. CONCLUSIONS: Chromosomal analysis provides prognostic information about overall survival in addition to that supplied by clinical data in patients with B-cell CLL.

Adult↗
PubMed1990

Structure of the granulocyte macrophage colony-stimulating factor gene in patients with the myelodysplastic syndromes.

DNA samples from 76 patients with the myelodysplastic syndromes, including 10 cases with a partial deletion of the long arm of chromosome 5 (5q-), were examined for structural rearrangements of the granulocyte/macrophage colony-stimulating factor (GM-CSF) gene. No abnormalities were detected, indicating that structural aberrations of this gene are not a feature of the myelodysplastic syndromes.

Colony-Stimulating Factors↗
PubMed1990

Prognostic factors in stage AO B-cell chronic lymphocytic leukaemia.

85 patients presenting to a single centre with stage AO B-cell chronic lymphocytic leukaemia (B-CLL) have been studied. The duration of follow-up has ranged from a minimum of 1 year to a maximum of 18 years with a mean of 6 years. 14 patients have had progressive disease and 23 patients have died, of whom nine had CLL-related deaths. We assessed the prognostic significance of the following parameters: age at presentation, sex, haemoglobin concentration, initial lymphocyte count, surface membrane phenotype, serum immunoglobulin levels at presentation and karyotype. None of these factors were predictive of survival, but there was a correlation between initial lymphocyte count, surface immunoglobulin MD lambda phenotype, and complex karyotypic abnormalities and disease progression. Two patients with a complex karyotype have been followed for more than 5 years without evidence of progression.

Adult↗
PubMed1990

Correlation of chromosome abnormalities with laboratory features and clinical course in B-cell chronic lymphocytic leukaemia.

141 patients with B-cell chronic lymphocytic leukaemia (B-CLL) have been studied for a minimum of 12 months and a maximum of 25 years. 30 of 133 patients (32.5%) had greater than 10% FMC7 positive peripheral blood lymphocytes and 19 of 131 patients (14.5%) had a serum or urinary paraprotein. At presentation 88 patients were stage A0, 18 A1, 18 A2, 11 B and six C. 44 (31%) had progressive disease and 42 (30%) died during the study period. 63 patients had a normal karyotype, 75 a clonal abnormality and in three no metaphases were obtained. The finding of a complex karyotypic abnormality was significantly associated with lambda surface phenotype (P less than 0.01), the presence of greater than 10% FMC7 positive cells (P less than 0.025), and the presence of a paraprotein (P = 0.025). Patients whose leukaemic cells had a complex karyotype and those with structural abnormalities of chromosomes 14 and 6 required treatment earlier than those with a normal karyotype.

Aged↗
PubMed1989

Detection of retrovirus in patients with myeloproliferative disease.

RNA-directed DNA polymerase (reverse transcriptase) activity was detected in platelets from 4/4 patients with primary proliferative polycythaemia (PPP), 7/7 patients with essential thrombocythaemia (ET), 1/4 patients with relative "stress" polycythaemia, 0/2 patients with secondary polycythaemia, and 0/3 normal subjects. The activity appeared to be particle-associated and was detected under conditions not appropriate for any known cellular enzymes. Active particulate fractions from 1 patient with PPP and 1 patient with ET were examined by electron microscopy and revealed objects with the features of retroviruses. Similar retrovirus-like particles were observed in 2/2 further patients with PPP and 2/2 further patients with ET but in 0/3 controls.

Blood Platelets↗
PubMed1989

Correlation of bone marrow colony growth in the myelodysplastic syndromes with the FAB classification and the Bournemouth score.

Erythroid and myeloid colonies were grown from the bone marrow of 81 patients with myelodysplasia and the median number of colonies correlated with the FAB classification and Bournemouth score. CFU-GM were increased in CMML compared to RAEB and RAEBt. BFU-E were higher in RA than in the other FAB subgroups. Patients with a high Bournemouth score had poorer CFU-GM and BFU-E growth than those with a low score.

Anemia, Refractory↗
PubMed1989

The application of X-chromosome gene probes to the diagnosis of myeloproliferative disease.

X-chromosome DNA probes for the phosphoglycerate kinase (PGK) and hypoxanthine phosphoribosyl transferase (HPRT) genes were used to study clonality in haemopoietic cells from 63 women with myeloproliferative disease, idiopathic erythrocytosis, secondary erythrocytosis or normal red cell volumes. A total of 25 women (39%) were heterozygous for one of the polymorphisms associated with these genes. Clonality was demonstrated in five out of six patients with polycythaemia vera (PV) and in three other patients with myeloproliferative disease. In all cases of PV, including the patient in whom clonality was not demonstrated, cultures of peripheral blood showed growth of endogenous erythroid colonies.

Clone Cells↗
PubMed1988

Absence of immunoglobulin and T-cell receptor gene rearrangements in myelodysplastic syndromes and acute nonlymphocytic leukemias.

The arrangement of the immunoglobulin and T-cell receptor genes has been analysed in 72 cases of primary myelodysplastic syndrome and 17 cases of acute nonlymphocytic leukemia. DNA was extracted from bone marrow aspirates, digested with at least two restriction enzymes, and hybridised with probes for the joining region of the immunoglobulin heavy chain gene, the constant region of the T-cell receptor beta chain gene, and the joining region of the T-cell receptor gamma chain gene. All cases showed germline arrangements of the immunoglobulin and the T cell receptor genes. Thus, true interlineage infidelity, myeloid to lymphoid, is a rare occurrence in myelodysplasia and in myeloid leukemias.

Acute Disease↗
PubMed1988

Detection of chromosomal 7 loss in myelodysplasia using an extremely polymorphic DNA probe.

Chromosomal loss is a characteristic feature of the myelodysplastic syndromes (MDS). A method is described which detects chromosomal 7 loss in MDS by DNA analysis using a specific hypervariable region gene probe which has been cloned from a human DNA fingerprint. Loss of one of the chromosomal 7 homologues was demonstrated in 10/118 MDS patients; the ten patients include all the five patients which had previously been shown to have monosomy 7 by cytogenetic analysis. This technique makes it feasible to study serial samples from large numbers of patients for loss of chromosomal material and could be readily applied to the study of other human malignancies.

Alleles↗
PubMed1988

Prognostic features of chronic myelomonocytic leukaemia: a modified Bournemouth score gives the best prediction of survival.

We have studied the clinical and laboratory features of 53 cases of chronic myelomonocytic leukaemia (CMML) defined according to the FAB criteria. A granulocyte count of greater than 16 X 10(9)/l or a monocyte count of greater than 2.6 X 10(9)/l correlated with a poorer survival, but the best predictor of poor survival was the modified 'Bournemouth' score in which one point each was allocated for Hb less than 10 g/dl, neutrophils less than 2.5 X 10(9)/l or greater than 16 X 10(9)/l, platelets less than 100 X 10(9)/l and bone marrow blasts greater than 5%. A score of 2 or more was predictive of poor survival (Chi2 = 10.25; P less than 0.001). Those patients with low monocyte and neutrophil counts and a low modified Bournemouth score tended to have a clinical course similar to refractory anaemia (RA) with an indolent course not requiring treatment and long survival whereas those with high monocyte and neutrophil counts and a high modified 'Bournemouth' score have a clinical course resembling that of refractory anaemia with excess of blasts (RAEB).

Aged↗
PubMed1988

CD3+ CD8+ T cell lymphocytosis masking B cell leukaemia.

A patient with CD3, CD8 positive lymphocytosis presented with features consistent with T cell chronic lymphocytic leukaemia/proliferations of large granular lymphocytes. The marrow and blood lymphoid populations (19.4 x 10(9)/l) contained more than 80% CD3 and CD8 positive cells with no evidence of a monotypic B cell population. A biopsy specimen of a vasculitic rash showed a diffuse infiltrate of CD3, CD8 positive cells into the upper dermis, consistent with T cell lymphocytic disease. After follow up for two years without treatment the blood lymphocyte count was 53 x 10(9)/l and was composed of cytologically small lymphocytes. A monoclonal SIg M D k lymphoid population (more than 90%) was demonstrable in sample blood and marrow aspirate. Gene rearrangement studies carried out on DNA extracted from peripheral blood lymphocytes at presentation and at two year follow up exhibited JH and Ck immunoglobulin gene rearrangement but no rearrangement of T cell receptor TcR gamma and beta genes. It is thought that this is the first well documented case of an aggressive CD8 positive lymphocytosis preceding, or in response to, an underlying B cell neoplasm.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1988

Chromosomal abnormalities in B-CLL.

Amongst 141 patients with B-CLL, 53% had an abnormal karyotype. Treatment free survival was shorter in those with karyotypic abnormalities, and especially in those with multiple abnormalities. Multiple abnormalities tended to be associated with progressive disease. Trisomy 12 alone carried no worse a prognosis than a normal karyotype. 49% of patients with stage AO disease had an abnormal karyotype.

Actuarial Analysis↗