CHOP-based chemotherapy is as effective as alternating PEEC/CHOP chemotherapy in a randomised trial in high-grade non-Hodgkin's lymphoma. Scotland and Newcastle Lymphoma Group.

The aim of this study was to test whether survival for patients with high-grade non-Hodgkin's lymphoma (NHL) can be improved with a non-cross-resistant regimen as compared to a CHOP-based regimen. This is a multicentre study comprising 325 adult patients, median age 58 years, with high-grade non-Hodgkin's lymphoma: patients of any age and performance status were eligible provided they were able to receive the drugs in the regimens. Patients were randomised to either B-CHOP-M (bleomycin, cyclophosphamide, doxorubicin, vincristine, prednisolone and methotrexate) or PEEC-M (methylprednisolone, vindesine, etoposide, chlorambucil and methotrexate) alternating with B-CHOP-M. At a median follow-up of 9 years, there was no significant difference in overall survival or disease-free survival between the two arms. Toxicities for the two regimens were equivalent. This study confirms that for relatively unselected patients with high-grade non-Hodgkin's lymphoma, an alternating multidrug regimen does not improve upon the results obtained with B-CHOP-M.

The effeCt of vitamin c supplements on serum cholesterol, coagulation, fibrinolysis and platelet adhesiveness.

The administration of ascorbic acid (1g/day) to healthy adults did not significantly influence the levels of serum cholesterol, plasminogen activator activity, plasminogen, fibrinogen, FR-antigen, partial thromboplastin time, platelet adhesiveness, a-1-antitrypsin or a-2-macroglobulin over the 3-month period of study.

Immunophenotyping of leukaemias by flow cytometry and APAAP: a two-year comparative analysis in hospital practice.

Using a panel of monoclonal antibodies for the immunophenotyping of haematological malignancies, we have made a direct comparison of the usefulness of indirect immunofluorescence using flow cytometry (IFC) alongside the alkaline phosphatase-anti-alkaline phosphatase (APAAP) immunoenzyme method. Analysis of 400 consecutive patient samples (blood and bone marrow) over a 2-year period, resulted in unequivocal phenotyping agreement by both methods in 98 per cent of cases. The positive results accounting for 2 per cent discordance were obtained by the APAAP method. The value of the technique in the clinical management of patients with leukaemia is documented together with guidelines for clinical laboratories.

Immunoregulatory T cells in B cell chronic lymphocytic leukaemia: evidence of a unique phenotype a flow cytometric study.

CD4+ T cells of 57 patients with B cell chronic lymphocytic leukaemia (CLL) were analysed for expression of CD45RA and CD29. The majority of CLL patients (33 cases) showed a novel coexpression of these markers on a significant proportion of CD4+ T cells; however, analysis of a single blood sample revealed no apparent prognostic value associated with the markers. Expression of CD45RA and CD29 correlated with parameters of immune function consistent with the known attributes of these markers.

Phenotypic abnormality of T cells in B cell non-Hodgkin's lymphoma.

CD4+ T cells of patients with B cell non-Hodgkin's lymphoma (NHL) were analysed for expression of CD45RA and CD29. It was found that CD45RA expression was significantly lower, and CD29 expression significantly higher, in lymphoma patients compared to normal controls. Moreover absolute numbers of CD4+ T cells were significantly lower in NHL patients, due to selective depletion of CD4+ CD45RA+ cells.

Microangiopathic haemolytic anaemia associated with malignant haemangio-endothelioma.

A case of microangiopathic haemolytic anaemia associated with malignant haemangio-endothelioma is described. It is suggested that haemolysis may have been due to mechanical trauma sustained by the red blood cells on passage through the tumour's abnormal vasculature.

Thrombocytopenic purpura as the sole manifestation of a recurrence of Hodgkin's disease.

A man with apparently quiescent Hodgkin's disease presented with acute severe isolated thrombocytopenic purpura. Splenectomy revealed macroscopic involvement with Hodgkin's tissue and cured the thrombocytopenia.

The effect of age on the fibrinolytic enzyme system.

Components of the fibrinolytic enzyme system, FR-antigen and fibrinogen, were measured in 20 healthy volunteers aged 20-40 years and in 61 elderly subjects aged 66-96 years. Plasminogen activator levels did not significantly differ between the 20-40 and 66-75 age groups, but were higher in those over 75. Plasminogen showed no change with age except for a fall in those over 75. Fibrinogen, FR-antigen, alpha(1)-antitrypsin, and alpha(2)-macroglobulin all rose with age, but the mean fibrinogen concentration fell in the very elderly.

Economic and laboratory considerations in screening for vitamin B12 deficiency in psychiatric practice.

Two alternative methods for detecting vitamin B(12) deficiency in a psychiatric population have been compared: the ;direct' approach by microbiological assay of serum vitamin B(12) levels in all patients, and the ;indirect' approach where all patients are first screened for antigastric parietal cell antibodies and thereafter all positive reactors and other ;high-risk' patients have serum vitamin B(12) assayed. The indirect approach was found to be cheaper.

The effect of age upon the coagulation system.

Factors V, VII, VIII, X, XI, and XII of the coagulation system, platelet count, and antithrombin III levels were assayed in 20 healthy volunteers aged 20-40 years and 61 elderly subjects aged 66-96 years whose skinfold thickness was also measured. Factors XI, XII, and antithrombin III levels tended to increase in women and decrease in men while factors X, VII, and V tended to increase in both males and females with advancing years. No age or sex differences were found in platelet counts or factor VIII levels. Factor VIII levels were inversely correlated with obesity in elderly males (r = -0.56, p < 0.005).

Non-cytotoxic antibodies in chronic lymphocytic leukaemia.

Non-cytotoxic Fc receptor blocking antibodies against autologous B lymphocytes were sought in sera from patients with chronic lymphocytic leukaemia (CLL), using a rosette inhibition assay. They were found in 11 of 52 (21%) of patients with CLL, but were not associated with previous blood transfusion or pregnancy, suggesting that they were unlikely to have resulted from allogeneic stimulation. Fc receptor blockade was more commonly detected in sera from patients with stage B rather than stage A CLL (Binet classification), though this did not achieve significance beyond the 90% level, and it was noted in 62.5% of those with lymphocyte doubling times of less than one year, compared with 36.3% of those whose lymphocyte doubling time was more than one year. The results indicate that autologous Fc receptor blocking antibody activity occurs in sera from patients with CLL, is more likely to be generated by the tumour itself than by allogeneic stimulation, and is associated with increased tumour load. Such antibodies may permit tolerance of tumour by the host.

Fertility in young men and women after treatment for lymphoma: a study of a population.

All young patients in the Grampian area attending the lymphoma review clinic who had received first line treatment for Hodgkin's disease and had attained complete remission without subsequent relapse were studied between 1980 and 1983. Chemotherapy with MVPP (mustine, vinblastine, procarbazine, and prednisolone) had more severe effects on the fertility of men than that of women; younger women and those taking oral contraceptives were more likely to retain fertility than those over 30 or not taking the pill at the time of chemotherapy, but these two effects could not be differentiated. Premature menopause was common after treatment with MVPP. Mantle radiotherapy had no discernible effect on gonadal function.

The effects of four drug regimens on sister chromatid exchange frequency in patients with lymphomas.

Patients undergoing first-line chemotherapy after diagnosis of lymphoma have considerable DNA damage in their peripheral blood lymphocytes, using sister chromatid exchange (SCE) frequency as a sensitive indicator. Different drug regimens produce different patterns of changes in SCE frequency. These may be related to their potential to induce second malignancies.

A possible case of chronic leukoerythroblastosis associated with t(12;14)(p13;q22) in bone marrow cells.

The case is presented of a 64-year-old man who has had recurrent psychiatric symptoms over several years, and now has minor evidence of a myeloproliferative disorder. He had a buccal carcinoma successfully treated 33 years previously, thus, the possibility of bone marrow infiltration has been excluded. An acquired translocation that was found in his bone marrow cells has not been previously reported in association with any neoplasm. The possible significance of the translocation to this patient is discussed.

Variation of SCE frequency in lymphocyte cultures from patients with Hodgkin's disease before, during, and after treatment.

Seven patients with newly-diagnosed Hodgkin's disease, having standard mustine-vinblastine-prednisolone-procarbazine therapy, had a large and regular pattern of rise in SCE frequency in their peripheral lymphocytes, which apparently started to fall before the end of the course (32 wk). In contrast, SCE frequency fell below normal in the lymphocytes of nine patients having mantle radiotherapy. Twenty-eight patients studied 2-13 yr after initial chemotherapy or radiotherapy for Hodgkin's disease had normal or near normal SCE frequencies.

Chromosome damage and sister chromatid exchanges in lymphocyte cultures from patients with two primary cancers.

Sister chromatid exchanges (SCEs) and chromosome damage were scored in lymphocyte cultures from 11 patients with two or more primary cancers and were compared with normal controls. None of the patients had a constitutional chromosome anomaly, but six showed evidence of chromosome instability, which could not be accounted for by treatment, expressed either as elevated SCE frequency or increased nonspecific chromosome damage and chromosome loss. Chromosome damage included major rearrangements as well as deletions and gaps. The possibility of common mechanisms in chromosome instability leading to susceptibility to a heterogeneous group of primary cancers is discussed.

Analysis of MDR1 and MDR3 multidrug resistance gene expression and amplification in consecutive samples in patients with acute leukaemias.

White blood cells from a total of 19 patients diagnosed as having acute lymphoblastic (ALL) or acute myeloid (AML) leukaemia were analysed (36 samples) for amplification and expression of the mdr1 and mdr3 genes. Nine of the patients had samples analysed at presentation and at subsequent stages of the disease (24 samples, including 4 at second relapse). Patients received standard MRC UK Trial remission-induction treatment protocols appropriate to disease and age. No amplification of either the mdr1 or mdr3 gene was found in any of the samples, and neither were mdr3 transcripts detected by dot-blot analysis using gene-specific probes. Transcripts of the mdr1 gene were found in only 2 ALL samples (of 10). However, mdr1 transcripts were detected in all AML patients and there was a significant increase in the transcript levels in these patients who went on to first and second relapse, compared with levels measured at presentation (P < 0.001). The results support the hypothesis that P-glycoprotein-mediated drug resistance may be a significant factor in tumour cell resistance to chemotherapy at relapse following initial induction-remission therapy for acute myeloid leukemia.

Evidence for a seasonal variation in the presentation of Hodgkins disease.

An analysis by month of diagnosis was made of 1359 cases of Hodgkins disease (HD) on the Scotland and Newcastle Lymphoma Group (SNLG) registry 1979-1992 to look for evidence of seasonality. A March peak was evident when all cases were analysed (p < 0.01). The histological subtypes nodular sclerosing (NS) and mixed cellularity (MC) showed a similar pattern (p < 0.05) while lymphocyte depleted (LD) and lymphocyte predominant (LP) had no demonstrable seasonal variation. In a breakdown by age and sex there was evidence of seasonality in both sexes but only under the age of 40. This provides further evidence for the heterogeneity of HD and supports the hypothesis that different factors are involved in the aetiology of this condition in younger compared to older patients.

N-acetyl-beta-D-glucosaminidase enzymuria in leukaemia and myelomatosis: effect of treatment in acute myeloblastic leukaemia and myelomatosis in adults.

The activity of the lysosomal hydrolase N-acetyl-beta-D-glucosaminidase (NAG) was measured in the urine of patients with leukaemia or myeloma. Elevated pre-treatment enzymuria was noted in all patient groups with acute myeloblastic leukaemias (AML) FAB type M4 or 5 displaying higher activities than AML patients FAB types M1-3, which in turn were higher than those found in patients with myelomatosis and chronic lymphocytic leukaemia. The ratio of the major isoenzymes of NAG, A/B was reduced significantly only in patients with AML. Following treatment, AML patients who entered remission demonstrated NAG levels which approached normal values. In those AML patients who were either in relapse, in the terminal phase of their illness or treated with aminoglycoside antibiotics, NAG enzymuria was similar to pre-treatment values. A reduction in urinary NAG levels and both serum and urine beta 2 microglobulin concentrations was also observed following treatment in myeloma patients. The use of enzymuria both as a guide to progress towards remission in AML patients and for assessing prognosis and progress in myeloma patients is discussed.

Non-Hodgkins lymphoma of the head and neck: experience in the Grampian area.

The records of 44 cases of non-Hodgkins lymphoma (NHL) presenting to the ear, nose and throat department in the Grampian area from 1980-1988 were examined in relation to site of occurrence, histology, age at presentation, clinical stage, treatment and survival. The median age was 67 years and there was a preponderance of high grade histology, especially in disease affecting the tonsil. Most deaths occurred in the first year; patients with high grade disease and those in stages three and four had a significantly poorer survival during the first year. The site of disease had no influence on survival.