Cytological features of 9q- deletions in AML.
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Adult↗
Biomedical subjects
F G Hayhoe
Publications and source records attributed to F G Hayhoe.
Cytochemical demonstration of 'platelet' peroxidase at the light microscope level.
A reliable and reproducible modified method was developed for the cytochemical demonstration of the so-called 'platelet' peroxidase at the light microscopy (LM) level. Interestingly, not only normal platelets and megakaryocytes showed the peroxidase activity, but also normal lymphocytes. As with the ultrastructural platelet peroxidase (PPO) method, myeloperoxidase (MPO) was also demonstrated in granulocytes. Peroxidase activity was exhibited by blast cells of acute myeloid leukaemia, including megakaryoblasts of megakaryoblastic leukaemia, by hairy cells of hairy cell leukaemia, by centroblasts of centroblastic lymphoma and by plasma cells of plasma cell leukaemia. The enzyme activity was also demonstrated in the mast cells of systemic mastocytosis. It seems that different forms of peroxidase are present in most haemic cells. Fixation and conditions of incubation are probably the determining factors for their demonstration. The method may allow further cytochemical discrimination at the LM level between blast cell populations which are negative for MPO by standard methods.
Blood Platelets↗
Histochemistry of dipeptidyl aminopeptidase (DAP) II and IV in reactive lymphoid tissues and malignant lymphoma.
A modified histochemical method was used to show the presence of dipeptidyl aminopeptidase (DAP) II and IV in fixed, freeze dried, cryostat sections of tonsils, lymph nodes, and skin. In 14 reactive tonsils and lymph nodes both enzyme reactions were largely confined to T dependent areas where scattered positive lymphocytes were shown in the paracortical zones, while lymphocytes of germinal centres (B dependent areas) were negative. In either site some macrophages showed strong positivity for both enzymes. In 23 lymph node and two skin biopsy specimens of non-Hodgkin's lymphoma the neoplastic lymphocytes of 12 B cell lymphomas were completely unstained, whereas in the 13 cases of T cell lymphoma the neoplastic lymphocytes showed variable reactions with positivity for DAP II in eight and for DAP IV in seven, both reactions being positive in four and negative in two. Touch imprints of a lymph node from a case of Hodgkin's disease showed that the Reed-Sternberg cells were unreactive for both enzymes. The histochemistry of DAP II and IV may supplement other histochemical and immunological markers in the cytological classification of lymphomas.
Dipeptidyl Peptidase 4↗
Cytochemical method for demonstrating magnesium-activated adenosine triphosphatase in haemic cells.
A modified cytochemical method was developed for demonstrating magnesium-activated adenosine triphosphatase in haemic cells. The enzyme was shown in a variety of normal and leukaemic, unfixed cells. The high sensitivity of this enzyme to all fixatives tried in this study hampered further exploration and characterization of this enzyme.
Bone Marrow↗
Principal results of the Medical Research Council's 8th acute myeloid leukaemia trial.
Between 1978 and 1983, 1127 patients with de-novo acute myeloid leukaemia (AML) were entered into the Medical Research Council (MRC)'s 8th AML trial. All received the same induction therapy consisting of daunorubicin, cytarabine, and 6-thioguanine--DAT (1 + 5). The 67% who entered complete remission were randomised to consolidation with two or six further courses of DAT. Adults under the age of 55 were randomised for central nervous system (CNS) prophylaxis with intrathecal cytarabine and methotrexate. Finally, those still in remission after 1 year of cytarabine and 6-thioguanine (AT) maintenance were randomised to receive either late intensification with cyclophosphamide, vincristine, cytarabine, and prednisolone (COAP) or continued AT. The median survival for the whole group was 12 months; the median duration of first remission was 15 months, with relapse-free survival at 5 years estimated at 18%. The factors most strongly associated with poor survival were performance status and age at presentation, but even among those over 60 years of age, half went into remission. Six courses of DAT consolidation gave a small advantage over two courses in reducing the number of late relapses but no significant survival advantage. Late intensification showed a marginally significant advantage over continued AT maintenance. The incidence of CNS relapse was low and unaffected by prophylaxis. The second remission rate varied from 10% when the first remission was shorter than 6 months to 61% when it had continued for more than 2 years. 40 patients received histocompatible allogeneic bone-marrow transplants in first remission. There was a high procedure-related death rate, particularly among patients over 30 years of age. Thus, initially at least, the transplanted group had shorter survival than a comparable group of chemotherapy-treated patients. Treatment specifications remained unchanged throughout the trial but those enrolled in the later half of the trial had a better (p = 0.003) survival.
Adolescent↗
Features affecting outcome during remission induction of acute myeloid leukaemia in 619 adult patients.
Six hundred and nineteen patients with de novo acute myeloid leukaemia, entered into the Medical Research Council's eighth trial of therapy have been studied. All patients were treated with the same remission induction regimen. Pretreatment variables comprising age, clinical status, haematological status and a detailed marrow cytology and cytochemistry score have been analysed. Poorer remission rates have been found in older patients, in those with lower Karnofsky scores and in patients with a platelet count of less than 25 X 10(9)/l. Leukaemias showing evidence of cytoplasmic maturation along the granulocyte and monocyte lines, as evidenced by granules, Auer rods, a high percentage of Sudan black positive blast cells and morphological and cytochemical abnormalities of neutrophils were associated with a higher remission rate. Marrow eosinophilia was a good prognostic feature. Nuclear features of immaturity, i.e. increasing numbers and prominence of nucleoli were associated with a low remission rate. Abnormalities of the erythroid series, notably Periodic acid-Schiff positivity which was present in 133 cases (22% of the total), was associated with a low remission rate. Patient age and pretreatment Karnofsky score were the most useful predictors of treatment outcome.
Adolescent↗
Ultrastructure and cytogenetics in seven cases of acute promyelocytic leukaemia (APL).
In the seven cases of acute promyelocytic leukaemia (APL) presented here we have studied the ultrastructural and cytogenetic features which are thought to be of particular significance in this disease. On the basis of our findings from the seven cases of APL described in detail, and our unreported results obtained for a large number of myeloid leukaemias other than APL, we conclude the following. Stellate rough endoplasmic reticulum, certain inclusion bodies and Auer rods having a tubular substructure are, if present, probably diagnostic of APL. However, these structures are not always observed in APL. Inflated rough endoplasmic reticulum is highly indicative of APL while slender cytoplasmic projections, convoluted or lobed nuclei and conspicuous bundles of cytoplasmic fibrils are very common in the abnormal promyelocytes of this disease. There is a strong correlation between the presence of conspicuous bundles of cytoplasmic fibrils and convoluted or lobed nuclei. Most of the APL cases showed the characteristic translocation t(15;17) and we could find no ultrastructural difference between the cases with the translocation and the single example of a normal karyotype.
Cell Nucleus↗
Comparative cytochemical study of dipeptidyl aminopeptidase (DAP) II and IV in normal and malignant haemic cells.
Modified cytochemical methods were used to show dipeptidyl aminopeptidases (DAP) II and IV in peripheral blood buffy coat preparations and bone marrow smears. In 23 normal buffy coats both enzymes were confined to lymphocytes. DAP II was found in T and B lymphocytes (about 80%) while DAP IV was restricted to T lymphocytes only (around 46%). In 11 normal bone marrows DAP II was found in 53% of the lymphocytes, as well as in plasma cells, macrophages, and occasional myeloblasts. DAP IV was found only in lymphocytes (around 32%). DAP II activity, but not DAP IV activity, was present in all of the mast cells in a case of systemic mastocytosis. Whereas DAP II was found, to a variable extent, in leukaemic myeloblasts, monoblasts, proerythroblasts, and in megakaryoblasts in 52 cases of acute myeloid leukaemia, DAP IV was not shown. Variable positivity to DAP II and DAP IV was found in the lymphoblasts in seven cases of acute lymphoblastic leukaemia, in 14 cases of B chronic lymphocytic leukaemia, and in three cases of non-Hodgkin's lymphoma. DAP II activity was variable compared with DAP IV activity, which was constantly reduced. Virtually all of the myeloma cells (96%) all of the myeloma cells (96%) in five cases of multiple myeloma and two cases of plasma cell leukaemia were DAP II positive and DAP IV negative. In 10 cases of hairy cell leukaemia most hairy cells were positive to DAP II (74%) with no demonstrable DAP IV activity. In a single case of Sézary's syndrome around 90% of the helper T cells were positive to DAP II with no DAP IV activity.
B-Lymphocytes↗
Review of British National Lymphoma Investigation studies of Hodgkin's disease and development of prognostic index.
A review of data from the British National Lymphoma Investigation (BNLI) studies of Hodgkin's disease (HD) done over the past 14 years shows (i) that systemic chemotherapy is appropriate for all clinical stages except I and IIA, and that MOPP (mustine, vincristine, procarbazine, and prednisone) courses are substantially more effective than MOP (the same without prednisone) but no better than the less toxic LOPP combinations (where chlorambucil replaces mustine); (ii) that local involved-field irradiation in stages I and IIA HD is as effective as wide-field in terms of both overall and recurrence-free survival; and (iii) that, histologically, nodular sclerosing HD can be divided into grades 1 and 2, the latter containing areas of lymphocyte depletion or numerous pleomorphic Hodgkin's cells. A multivariate analysis of factors influencing prognosis in clinical stages I and IIA disease shows that laparotomy has no significant effect but that age, sex, erythrocyte sedimentation (ESR), the presence or absence of mediastinal involvement and, especially, pathological grade are the most important factors influencing overall survival, while ESR, pathological grade, and stage of disease (I or II) correlate with recurrence-free time. A prognostic "survival" index was developed; an index of greater than 7.5 indicated a poor prognosis and that chemotherapy was perhaps more appropriate than local radiation. Laparotomy is no longer justified as a routine procedure in staging HD, although it may still be useful in special circumstances and in some research investigations.
Adult↗
Clostridium difficile in haematological malignancy.
Twenty patients with haematological malignancies who developed Clostridium difficile bowel infection or colonisation are described. All isolates of C difficile were toxigenic in vitro and faecal cytotoxin (toxin B) was detected in 20/26 episodes. Ten of 20 episodes with detectable faecal cytotoxin were associated with typical antibiotic associated diarrhoea. In the other 10 episodes (nine patients), there was a severe unusual illness which was associated with detection of C difficile. The unusual features of the illness were pronounced jaundice (total bilirubin greater than or equal to 44 mumol/l), abdominal pain and distension, and initial constipation followed either by diarrhoea or by large bowel stasis. Four of these patients died within seven days. Bacteraemia was often a presenting feature in neutropenic patients subsequently shown to have C difficile. This was not the case in non-neutropenic patients. Bacteraemia was commonly polymicrobial and in two cases C difficile was isolated from blood culture. The clinical implications of recognition of this atypical C difficile associated syndrome are discussed.
Adolescent↗
Cytochemistry of the acute leukaemias.
The use of the Romanowsky staining technique, Sudan Black B, the periodic acid-Schiff reaction and methods for revealing peroxidase, acid and alkaline phosphatases and butyrate, acetate or chloroacetate esterases for identifying and discriminating subvarieties of acute leukaemia at the light microscope level is reviewed and the results of their application in a recent study of the first 720 cases admitted to the Medical Research Council's 8th Acute Myeloid Leukaemia trial summarized. The distribution of varieties of acute myeloid leukaemia and the relevance of age and cytochemical findings to clinical prognosis is presented. Identification of the predominant primitive cell - myeloblast, promyelocyte, monoblast, and others - appears to have little prognostic significance. In fact, the presence of periodic acid-Schiff positive erythroblasts is a bad prognostic sign. The association of certain cytochemical findings with the 15;17 translocation and acute promyelocytic leukaemia, especially the patterns of esterase positivity in Auer rods and the Sudan Black, peroxidase, periodic acid-Schiff and esterase findings characteristic of the 8;21 translocation are illustrated. Cytochemical features helpful in distinguishing acute megakaryoblastic leukaemia, notably the periodic acid-Schiff reaction, differential esterase reactivities and 5'-nucleotidase, are discussed and illustrated. Brief reference is made to the cytochemical differentiation of lymphoblastic leukaemias. Details of a technical method for the demonstration of 5'-nucleotidase are given.
Acute Disease↗
A further study on quicker re-entry of chromosomally abnormal cells to active proliferation and preferential death of chromosomally normal cells during ageing of specimens in acute myeloid leukemia (AML).
Quicker re-entry of chromosomally abnormal cells to active proliferation under culture conditions was observed in cultured peripheral blood samples, old or fresh, but not in cultured bone marrow samples. In 10 patients with AML studied using peripheral blood, the mitotic index (MI) rose after 24 h in culture and reached a peak after 48 h in culture in AA patients (with all abnormal karyotypes); the MI rose after 24 h in culture and reached a peak after 48, 72 or 96 h in culture in AN patients (mixed normal and abnormal karyotypes); the MI remained at much lower level until after 72, 96 or 120 h of culture in NN patients (all normal karyotypes). The MI at 24 and 48 h of culture was significantly higher in AN and AA patients than in NN patients. A significantly increased frequency of chromosomally normal cells after prolonged culture was observed in one patient with t(8;21). The results of this study also suggest that chromosomally normal cells are more likely to die off than are abnormal ones during ageing of specimens.
Aneuploidy↗
An unusual translocation, t(3;8), and deletion of chromosome 21 in acute myeloid leukemia.
This report describes a case of acute myeloid leukemia (AML) in which there was an unusual karyotypic abnormality involving chromosomes #3, #8, and #21. The clinical and hematologic features are described and cytogenetic findings are discussed in relation to previously reported variants of the translocation t(8;21) in AML. The breakpoint at 8q22 is a consistent feature in these cases.
Adult↗
Groups of darkly stained chromosomes may be artifacts.
Groups or conglomerations of darkly stained chromosomes (GDSC) observed in this study appeared to be artifacts as they were strictly technique dependent. Two methods of cell fixation were compared. In method I, fixative was added drop by drop to cell pellets and agitated continuously over a rotamixer. In method II, a few drops of fixative were added to hypotonic solution suspended with cells and mixed using a Pasteur pipette. In 11 patients with acute myeloid leukemia (AML) and in one patient with preleukemia studied using method I, no GDSC were found in the total of 325 metaphases examined. In 36 patients with AML, one with Klinefelter's syndrome and one with neutropenia studied using method II, GDSC were found in 18 patients. A further comparative study using different methods for cell fixation was performed in three patients. The frequency of cells with GDSC varied sharply with different methods used in two patients. In one patient the cells with GDSC were analyzed in detail. The number of darkly stained chromosomes in each cell was found to vary from 4 to 14 with a mean of 8.26 and D- and G-group chromosomes were preferentially involved.
Adult↗
8;21 translocation in acute granulocytic leukaemia: cytological, cytochemical and clinical features.
Thirty patients with the 8;21 translocation and three with closely related variants have been studied. Ages ranged from 3 to 64 years (mean 28.3). Thirty-one were entered into the MRC's 8th Acute Myeloid Leukaemia Trial. Twenty-nine (88%) achieved complete remission. Marrow smears from most patients showed granulocytic maturation (M2, FAB classification) with characteristic abnormalities, but at least six showed predominantly myeloblastic (M1) morphology. The blast cells were markedly heterogeneous with regard to size and nuclear cytoplasmic ratio. Typical staining patterns were observed in the blast cells using Sudan black B and diaminobenzidine peroxidase stains, and to a lesser extent with periodic acid-Schiff and chloroacetate esterase. Butyrate esterase was negative in all cases. Auer rods were present in the granulocyte precursors in 31 cases and in eosinophil precursors in two cases. In most cases the existence of the translocation was predicted from the cytological and cytochemical findings. Seven patients developed solid leukaemic deposits, principally in the mastoid cavities, orbital cavities or thoracic spine (extradural).
Adolescent↗
The characterisation of monoclonal antibodies against haemopoietic cells: comparison of an immunoperoxidase method with fluorescence activated cell sorting.
Nucleated cells from normal human peripheral blood and bone marrow have been analysed with 2 rat monoclonal antibodies of known specificity, one (YAML 555.6.6) directed against the P28,33 complex (anti-HLA-DR), and the other (YAML 501.4.4) directed against leucocyte common antigen (anti-LCA). The patterns of reactivity with an indirect immunoperoxidase method on fixed smeared cells were in close agreement with those obtained with a fluorescence activated cell sorter. A further new monoclonal antibody of unknown antigen specificity (YAML 537.2) reacts with an intracellular antigen present in neutrophils and their precursors from the promyelocyte stage onwards, megakaryocytes, and a proportion of monocytes, but not with eosinophils, nucleated red cells or lymphocytes. This reactivity could not be demonstrated using the fluorescence activated cell sorter. The immunoperoxidase method allows the identification of individual positive and negative cells and therefore provides a method of identifying minor reactive and non-reactive cell populations in a heterogeneous cell sample such as normal bone marrow. Cytoplasmic binding sites can be differentiated from membrane binding.
Animals↗
Alkaline phosphatase in haematology.
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Alkaline Phosphatase↗
5'-Nucleotidase in lymphocytes from various clinical disorders.
The enzyme 5'-nucleotidase (5'-N) was demonstrated cytochemically in blood cells using a modification of the Wachstein and Meisel technique [30]. In peripheral blood the activity was found to be localised mainly in the cell membrane of lymphocytes. A semiquantitative score of 5'-N positivity, was assessed in lymphocytes from eight normal donors and 60 patients with various types of leukaemia and lymphoma. The lymphocyte score of 5'-N was slightly reduced in CML and AML but markedly reduced in most lymphoproliferative states tested. The only supranormal activity was found in two of 18 cases of CLL.
5'-Nucleotidase↗