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Biomedical subjects

D Catovsky

Publications and source records attributed to D Catovsky.

At least 307 records · Page 17Linked to original sources
PubMed1987

Biochemical mechanisms of deoxycoformycin toxicity in chronic leukemias.

The in-vitro effects of deoxycoformycin (dCF) on dATP, NAD, ATP and DNA strand breaks have been evaluated in the cells from 42 patients with various types of chronic lymphoid leukemia. These included 18 with B-cell chronic lymphoid leukemias of different types (BCL); 10 with hairy cell leukemia (HCL) and 14 with T-cell chronic lymphoid leukemias of different types (TCL). The dATP concentrations in HCL, BCL and TCL increased from means of 2.9, 1.8 and 3.0 to 100.3, 68.2 and 51.3 pmol/10(6) cells respectively after 2 h with 10(-5) M dCF and 10(-4)M deoxyadenosine. After 18-24 h, the NAD levels and total double-stranded DNA decreased to 37 and 12.5% (HCL) to 36 and 21.6% (BCL) and 40 and 20.5% (TCL) of control values respectively. Similar decreases were observed in ATP levels. The results do not suggest that these measurements in vitro would predict which patients with these disorders will respond to dCF therapy. Although HCL responds particularly well to dCF in vivo, no difference in the in-vitro effects of dCF studied here could be detected between cases of HCL and the other types of chronic leukemia.

Adenosine Triphosphate↗
PubMed1987

Clinical and laboratory features of de novo acute myeloid leukaemia with trilineage myelodysplasia.

Primary myelodysplastic syndromes progress to acute myeloid leukaemia (AML) in about 30% of cases. We have sought evidence of pre-existing trilineage myelodysplasia (TMDS) using the FAB criteria (1982) in 160 consecutive cases of primary de novo AML. TMDS was found in 24 cases (15%) including two of 33 cases of M1 (6%), four of 40 cases of M2 (10%), none of 18 cases of M3, five of 31 cases of M4 (15%), six of 30 cases of M5 (20%), all of six cases of M6 and one of two cases of M7. The median presentation bone-marrow blast-cell count in the 24 AML/TMDS cases was 53% (30-90%) and 82% (45-100%) in the 136 cases of AML without TMDS. 60% of the AML/TMDS bone-marrow aspirates contained fewer than 60% of blasts compared with only 11% of those from AML without TMDS (P less than 0.001). In AML the occurrence of symptomatic cytopenias when the marrow blast-cell count is below 60% and the peripheral blood blast-cell count is below 20% is highly correlated with dysplastic haemopoiesis (P less than 0.001).

Adolescent↗
PubMed1987

Alpha, beta and gamma T-cell receptor genes: rearrangements correlate with haematological phenotype in T cell leukaemias.

We have studied the arrangement of the alpha, beta and gamma T cell receptor (TCR) genes in 27 patients with T cell lymphoproliferative disorders. Nine patients had acute lymphoblastic leukaemia (T-ALL), nine patients had prolymphocytic leukaemia (PLL), six patients presented with a T-CLL/T-lymphocytosis syndrome, two patients had Sezary syndrome (SS) and one patient had HTLV-I positive T-cell leukaemia/lymphoma (ATLL). alpha TCR gene rearrangement could be demonstrated by the use of three available probes in only one case. By contrast, both beta and gamma TCR gene rearrangement could be demonstrated by Southern blot analysis of DNA samples digested with appropriate restriction enzymes in the majority of cases. In general, when rearrangements were present they involved both alleles. The proportion of rearranged chromosomes was lower in T-ALL than in other forms of T-cell leukaemia and it was lower in cases with the CD4-/CD8+ phenotype than in those with a CD4+/CD8- phenotype. In three out of 34 cases of B-cell leukaemia the TCR beta-gene but not the TCR gamma-gene was rearranged, just as in two out of 26 cases of T-cell leukaemia the immunoglobulin (Ig) heavy chain but not the light chain genes were rearranged. These data suggest that development of the machinery required for gene rearrangement may precede commitment to B or T cell lineage. The use of this technique is especially useful for the classification of cases of ALL in which the cells are negative with respect to most current phenotypic markers and in cases of T cell lymphocytosis in which the finding of a gene rearrangement identifies a monoclonal cell population.

Adolescent↗
PubMed1987

The relationship between chronic lymphocytic leukaemia and prolymphocytic leukaemia. IV. Analysis of survival and prognostic features.

The prognostic value of biological, clinical and laboratory features was analysed in a series of 265 patients with chronic lymphocytic leukaemia (CLL) and prolymphocytic leukaemia (PLL). On univariate analysis seven features were shown to influence significantly the survival of the whole group of patients: absolute prolymphocyte count (ABS PROL), percentage of prolymphocytes (%PROL), WBC, spleen size, age, intensity of surface-membrane immunoglobulin (SmIg) and mouse (M) rosettes. Multivariate regression analysis of these features showed that only ABS PROL and spleen size had independent prognostic significance. The survival in PLL (38 cases) was significantly shorter than in CLL (227 cases) (median survival = 3 and 8 years, respectively). Patients with CLL with an increased %PROL (11-55%), defined as CLL/PL, could be divided into two groups: those with ABS PROL less than or equal to 15 X 10(9)/l (26 cases) fell within the 'standard-prognostic risk' for typical CLL (i.e. less than or equal to 10% PROL), whereas the survival outlook for the cases with ABS PROL greater than 15 X 10(9)/l (40 cases) was as bad as for PLL. A scoring system was generated with the four features that showed high prognostic significance: ABS PROL, spleen size, SmIg and M-rosettes. The score proved to be superior to any single feature as a predictor of survival, being especially useful in the analysis of the CLL/PL group: cases with high scores (greater than 2) had a median survival of 2.5 years, while the median has not been reached for those with low scores (less than or equal to 2). We suggest that this scoring system may help to identify the cases of CLL/PL that behave as PLL, and as such may benefit from different treatment.

Humans↗
PubMed1987

'Pseudo-lymphoid' leukaemia with unusual features: ultrastructural, immunological, cytogenetic and molecular studies.

An unusual case of 'pseudo-lymphoid' leukaemia is described. The leukaemic cells resembled small, mature lymphocytes but lacked B- and T-cell membrane markers as well as immunoglobulin (Ig) and T-cell receptor gene rearrangements. They showed, instead, features of early myeloid cells since they expressed 2 myeloid antigens, CDW13 and My9, and displayed peroxidase activity demonstrable by electron microscopy (EM) on unfixed cells. Cytogenetic studies showed monosomy 5, t(4;17) (p12;p11), t(2;3)(p23;q14) and an abnormal chromosome 12. Abnormalities of chromosomes 4 and 5 have been previously associated with 'pseudo-lymphoid' leukaemias. This case illustrates the value of sensitive methods for the characterization of blast cells and for the precise diagnosis of leukaemias with apparent 'lymphoid' morphology.

Antibodies, Monoclonal↗
PubMed1987

Identical twin marrow transplantation for 5 patients with chronic myeloid leukaemia: role of DNA finger-printing to confirm monozygosity in 3 cases.

5 patients with chronic myeloid leukaemia (CML) have been treated by BMT from identical twin donors. Syngeneity of the twins was established by conventional methods in the first 2 patients. These included the similarity of phenotype, dermatoglyphics and analysis of red cell isoenzymes and blood groups. 2 of the other patients had received multiple blood transfusions prior to referral for BMT thereby invalidating red cell analysis. However genetic identity was confirmed in these patients by the method of DNA 'finger-printing' which demonstrated identical restriction-fragment length polymorphisms. Conclusive proof of syngeneity in twins prior to BMT is important since it obviates the need for T-cell depletion and/or post-graft immunosuppression to prevent graft-versus-host disease (GVHD). All 5 patients were conditioned with high-dose chemoradiotherapy prior to BMT and all patients are alive and disease-free at a median follow-up of 12 months. In conclusion, we report a new, reliable method for determining syngeneity of twins which has bearing on the technical approach to BMT.

Adult↗
PubMed1987

Primary splenic hairy cell leukaemia: a case report and review of the literature.

Hairy cell leukaemia affecting primarily the spleen is a very rare feature of this disease at presentation. Splenectomy in such cases would seem to provide a cure. We report a case of primary splenic hairy cell leukaemia in which clinical and haematological remission were achieved after splenectomy, and we review the literature.

Blood Cell Count↗
PubMed1987

Different reactivity of monoclonal antibodies against common acute lymphoblastic leukaemia antigen (CD10).

The reactivity of five monoclonal antibodies J5, OKB-cALLA, Nu-N1, Nu-N2 and VIL-A1 against the common acute lymphoblastic leukaemia (common-ALL) antigen (glycoprotein 100, CD10); was investigated by indirect immunofluorescence in cell suspensions, and by immunoperoxidase in cytocentrifuge slides of ALL, chronic B cell lymphoproliferative disorders, and plasma cell dyscrasias. The five monoclonal antibodies gave similar positive results with both techniques only in samples of ALL. J5 was positive in variable degrees by immunofluorescence in the majority of B cell disorders examined but this was not confirmed by immunoperoxidase. OKB-cALLA reacted in a similar way to J5 in both techniques, although with a lower percentage of cells by immunofluorescence. Nu-N1, Nu-N2, and VIL-A1 were mainly negative when tested by both immunofluorescence and immunoperoxidase in B cell disorders other than ALL and therefore seemed to be more specific for the diagnosis of common-ALL.

Antibodies, Monoclonal↗
PubMed1987

Splenic B cell lymphoma with circulating villous lymphocytes: differential diagnosis of B cell leukaemias with large spleens.

The clinical, haematological, morphological and histological features of a series of 22 patients presenting with splenic lymphoma with circulating villous lymphocytes were assessed and compared with those of patients with other forms of chronic B cell leukaemia in an attempt to differentiate this condition from hairy cell leukaemia, prolymphocytic leukaemia, and chronic lymphocytic leukaemia, with which this condition has many features in common. The disease was twice as common in men than in women, with a mean (SD) age at diagnosis of 72 (9) years, and the most consistent presenting feature was massive enlargement of the spleen, which showed white and red pulp disease with a plasmacytic component. Small monoclonal bands were found in 60% of cases.

B-Lymphocytes↗
PubMed1987

Cytochemical profile of megakaryoblastic leukaemia: a study with cytochemical methods, monoclonal antibodies, and ultrastructural cytochemistry.

A cytochemical study using: Sudan black B; alpha-naphthyl acetate (ANAE) staining; estimation of alpha-naphthyl butyrate (ANBE) esterase activity; acid phosphatase activity; and 5' nucleotidase activity was carried out in 15 cases of megakaryoblastic leukaemia. These included cases of M7 acute myeloid leukaemia and blast crises of chronic granulocytic leukaemia. The megakaryoblastic nature of the blasts was first established using two monoclonal antibodies against platelet glycoproteins, and by estimating the platelet/peroxidase reaction at ultrastructural level. Our findings suggest that megakaryoblasts have a typical cytochemical profile comprising positive ANAE staining and acid phosphatase activity with a predominant localisation in the Golgi zone and negative or weak ANBE activity. A similar positive cytochemical pattern was also found in five cases of erythroleukaemia (M6). The specificity of the 5'nucleotidase activity for megakaryoblasts was not confirmed. In most cases of megakaryoblastic leukaemia there was no 5'nucleotidase activity only two cases showed positive reactions--reactions were positive in several cases of myeloblastic and lymphoblastic leukaemia. We suggest that cytochemical methods may be useful in diagnosing M6 and M7 acute leukaemia because less than 40% of leukaemic cells react with specific monoclonal antibodies.

5'-Nucleotidase↗
PubMed1987

Splenectomy in advanced chronic lymphocytic leukaemia.

A group of 20 patients with stage C chronic lymphocytic leukaemia (CLL) and marked splenomegaly refractory to anti-leukaemia treatment was evaluated in relation to clinical course and survival after splenectomy, and compared with a control group of non-splenectomised CLL patients at the same disease stage. Patients in the former group showed a significant clinical improvement after splenectomy, being reallocated to, and maintained in, stages A (85%) or B (10%) for more than 24 months. Ten patients were still alive 24-135 months after splenectomy. The 10 deaths observed in the group of splenectomised patients occurred 4-69 months after surgery, due to disease progression and/or immunoblastic transformation (4 cases), infectious complications (3 cases) and unrelated causes (3 cases). Analysis of survival from diagnosis showed a significantly better prognosis for patients in the splenectomised group (median survival 10 years, as compared to 3.5 years for the control group). The same statistical difference, p less than 0.001, with better life expectancy for splenectomised patients, was observed when the survival was calculated from the time of progression to stage C. These results strongly suggest a beneficial role for splenectomy in advanced CLL with significant splenomegaly, when the accumulation of resistant lymphoid cells precludes an adequate control of the disease by conventional forms of treatment.

Evaluation Studies as Topic↗
PubMed1987

Markers of differentiated B cell leukaemia: CD22 antibodies and FMC7 react with different molecules.

FMC7, a monoclonal antibody used extensively to characterize B cell leukaemias of differentiated phenotype (prolymphocytic, hairy cell, and similar leukaemias) was compared directly with antibodies of the CD22 cluster, which also react with B cells at a late stage in differentiation. Detailed comparison shows that the reaction spectrum, though similar, is not identical. Differences were particularly prominent in chronic lymphocytic leukaemia (CLL) and non-Hodgkin's lymphoma (NHL). Binding studies show that the antibodies react with different antigenic determinants, and immunochemical studies show that they react with different molecules. The FMC7 antigen, not previously characterized, was shown to be a protein of apparent molecular weight 105,000, by immunoblotting after electrophoresis of membrane extracts.

Antibodies, Monoclonal↗
PubMed1987

A t(8;14)(q24;q32) in a T-lymphoma/leukemia of CD8+ large granular lymphocytes.

Chromosome studies in a case of T cell lymphoma/leukemia, in which a high proportion of the dividing cells had a t(8;14)(q24;q32) similar to that seen in Burkitt's lymphoma, are described. The tumor cells had a mature T cell phenotype (TdT-,CD3+,CD8+,CD4-) and were morphologically large granular lymphocytes and immunoblasts, both cell types with similar lysosomal granules in the cytoplasm. The immunoglobulin heavy chain gene and the T cell receptor beta chain gene were not rearranged, while the T cell receptor gamma chain gene was polyclonally rearranged. Mitoses were obtained only from spontaneously dividing cells in the absence of mitogens; 49 of the 50 metaphases analyzed were chromosomally abnormal and had a t(1;22)(q12;q13) and dup(1)(q31q32) in all of them; 48 metaphases had in addition a t(8;14)(q24;q32) which presumably arose during clonal evolution. The latter may be associated with the aggressive behavior of this T cell disorder by comparison with other proliferations of large granular lymphocytes. Although abnormalities involving 14q32 are characteristic of B cell disorders, they have also been described in T cell malignancies, suggesting that genes transcribed in T cells and/or oncogenic sequences significant in T cell neoplasia are present in 14q32.

Adult↗
PubMed1987

Cytogenetic studies on prolymphocytic leukemia. II. T cell prolymphocytic leukemia.

We report chromosome abnormalities in 15 cases of T cell prolymphocytic leukemia (T-PLL). All cases were characterized by clinical, morphological, and membrane marker analysis. The most frequent abnormality was an inv(14)(q11q32) observed in nine cases. The T cell receptor (TCR) alpha chain gene is localized to 14q11 and the immunoglobulin heavy-chain gene to region 14q32. Four cases also had translocations involving 14q11. Trisomy or multisomy for 8q resulting from an i(8q) or from rearrangements with 8p12 as the breakpoint was observed in nine cases, and a deletion of 6q was found in four cases. Trisomy or partial trisomy for 7q was observed in four cases, of which two had abnormalities of band 7q35 to which the TCR beta chain gene is mapped. The expression of Tac antigen, investigated in 27 cases of human T cell leukemia virus I-negative chronic T cell leukemia, which included the 15 cases of T-PLL, showed a good correlation with abnormalities of 7q35. Our studies on chronic T leukemias suggest that inv(14)(q11q32) and trisomy for 8q are abnormalities characteristic of T-PLL.

Antibody Diversity↗
PubMed1987

Immunoglobulin gene rearrangements in hairy cell leukemia and other chronic B cell lymphoproliferative disorders.

Immunoglobulin gene rearrangements have been investigated in 11 patients with hairy cell leukemia (HCL), 11 with prolymphocytic Leukemia (PLL), and 34 with chronic lymphocytic leukemia (CLL). Heavy and Light Ig chain gene probes have been used, and Ig genes were found in a rearranged configuration in all cases. Production of kappa and lambda light chains correlated with the respective gene rearrangements. With respect to the heavy chain locus, we found that in 6 of 21 cases of kappa-producing CLL only one allele was rearranged, whereas both alleles were rearranged in nearly all cases of lambda-producing CLL and either kappa- or lambda-producing HCL and PLL. Our data confirm the B cell nature of HCL and lead us to suggest that HCL derives from the clonal expansion of a cell at a later developmental stage than in CLL and PLL.

B-Lymphocytes↗
PubMed1987

Immunological reconstitution after bone marrow transplant with Campath-1 treated bone marrow.

Immunological reconstitution after allogeneic bone marrow transplant (BMT) was studied in 20 patients who received Campath-1 treated bone marrow. The peripheral blood lymphocyte phenotype was analysed with a panel of monoclonal antibodies at 3, 6 and 12 months. T cell proliferative capacity was evaluated by stimulation with PHA and Con A and in the mixed lymphocyte reaction (MLR). Natural killer (NK) cell activity was analysed against the K562 cell line at specified times after BMT in nine patients. Absolute numbers of T lymphocytes were reduced in all patients at 3 and 6 months. A marked decrease in the number of CD4+ cells persisted beyond 12 months. CD8+ cells regenerated more rapidly and reached normal at 6 months. No correlation was found between changes in lymphocyte subpopulations and the presence of graft-versus-host disease or cytomegalovirus infection. B cells recovered rapidly and maintained normal numbers throughout the study. A moderate increase in HNK1+ (Leu7) cells was observed at 3 and 6 months simultaneously with a low expression of NK15 (Leu11) and OKM1 antigens at 3 and 6 months, suggesting the presence of immature NK cells early after the transplant. A profound decrease of T cell proliferative capacity was observed both after mitogen stimulation and in the mixed lymphocyte reaction. NK cell activity was raised during the first month after transplant in all but one patient but no correlation was found with the presence of GVHD or cell marker analysis.

Adolescent↗