C. O'brien

Hodgkin's disease: case control epidemiological study in Yorkshire.

This is the first report of a case-control epidemiological study on lymphomas and leukaemias occurring in Yorkshire during 1979-84. This paper deals with the results of the Hodgkins disease analysis comprising 248 cases and 489 controls. The results indicate support for previous work with respect to small family size and past history of infectious mononucleosis. Positive observations made in a previous pilot study are also confirmed and extended with respect to associations with certain chronic skin lesions, dental anaesthesia and familial factors. Negative associations are described with respect to X-ray exposures and cigarette smoking. It is proposed that these results fit into a general hypothesis that these conditions are the result of interaction between infectious agents and altered immunity in those persons genetically predisposed.

Chronic lymphocytic leukaemia: case control epidemiological study in Yorkshire.

This is the second report of a large case control study of lymphoma/leukaemia occurring in Yorkshire during 1979-84, and deals with chronic lymphocytic leukaemia presenting either in its haematological (CLL) or more solid lymphomatous (malignant lymphoma-lymphocytic or MLL) forms. In all, 330 cases and 561 controls were interviewed. The results support the concept that CLL/MLL is a condition of multiple aetiologies with evidence for genetic predisposition through an excess of family cases, immune perturbation demonstrated by excessive previous skin diseases and phenylbutazone use, and viral involvement shown by links with infectious diseases and multiple sclerosis.

Prognostic indicators in centroblastic-centrocytic lymphoma.

The prognostic importance of ploidy and proliferative index (%S + G2) assessed by flow cytometry, mitotic and centroblast counts, and histological growth pattern were evaluated in biopsy specimens taken before treatment from 60 cases of centroblastic-centrocytic non-Hodgkins lymphoma. Cases with a high proliferative index (greater than or equal to 18%) or DNA aneuploidy showed significantly poorer survival than those with a low proliferative index (less than 18%). A high mitotic count was also associated with a poor prognosis. On multiple regression analysis the flow cytometric assessments and mitotic counts were significant predictors of survival. Assessments of proliferative activity clearly have prognostic potential in centroblastic-centrocytic lymphoma and may permit more accurate characterisation of individual tumours.

DNA content and prognosis of non-Hodgkin's lymphoma.

Ninety cases of non-Hodgkins lymphoma diagnosed prior to the use of modern therapeutic regimens (1963-67) and 88 cases treated with such chemotherapy (1980-85) were studied using conventional morphology and flow cytometry. DNA aneuploidy as determined by flow cytometry was more common among high grade (38%) than low grade (19%) tumours (P less than 0.01). Measurements of proliferative index (S + G2 phase cells) revealed significantly increased values for high grade as compared with low grade lymphomas (P less than 0.001). In the first group of cases (1963-67) the relationship between histological grade and survival just failed to reach statistical significance over the long term (20 yr) (P = 0.1) but proved significant over 3 yr (P = 0.012). Differences in ploidy and proliferative index status were not associated with survival. In the second patient group (1980-85) attainment of complete remission following chemotherapy was associated with the presence of DNA aneuploidy in high grade tumours (P less than 0.05). The limited follow up of this group precluded assessment of survival in relation to ploidy.

Yorkshire Case Control Study of Leukaemias and Lymphomas Parallel Multivariate Analyses of Seven Disease Categories

Between 1980 and 1986 a case control study of leukaemias aid lymphomas in Yorkshire conducted face to face interviews on 1362 cases and 2442 age and sex matched hospital controls. Case diagnoses were histopathologically confirmed and grouped into non-Hodgkins lymphomma (NHL), Hodgkins Disease (HD), malignant lymphocytic lymphoma (MLL.), chronic lymphocytic leukaemia (CLL), acute myeloid leukaemia (AML), chronic myeloid leukaemia (CML) and acute lymphoblastic leukaemia (ALL). Multivariate analyses were completed on each separate disease to evaluate risk factors relating to past medical history, occupation, environmental exposures and social contact variables. The results show a significant association (with OR adjusted for other risk factors) between a family history of leukaemia/lymphoma and HD (OR = 4.29), NHL (OR = 1.98) and AML (OR = 6.36). For HD other cancers in the family also conveyed a significant risk (OR = 1.61). Use of heart drugs l(and heart disease) was linked to the chronic leukaemias (CML, CLL). A previous cancer and NHL, CLL and AML were associated even after adjustment for radiotherapy. A complex set of risk factors including prior skin lesions and steroid use showed significant links with HD, NHL and CLL., Increasing risk of NHL was linked to small family size. A significant excess of NHL cases reported exposure to glues and similarly ALL cases with agricultural chemical exposure. There present data provide both confirmatory and novel results. Overall they concur with the hypothesis of a multifactoral aetiology encompassing both genetic and immunological components.

Variation in lymphoma incidence within Yorkshire Health Region

The spatial distribution of new cases of lymphoma occurring in Yorkshire between 1978 and 1982 has been studied. Administrative districts were used as the basis for analysis and differences in age standardised incidence rates between districts were determined. Excessive rates for NHL were found to occur in Scarborough, York and Leeds districts. In addition an analysis contrasting broadly urban and rural districts showed an excess of NHL in rural areas, particularly of the follicular subtypes.

Hodgkin's disease: a flow cytometric study.

Flow cytometry was performed on paraffin embedded tissue from 115 cases of Hodgkins disease. Thirteen (11%) tumours were aneuploid with no significant difference between the histological subgroups. The median proliferative index was 14%, and the highest values were found in the NS2 (16.4%) and lymphocyte depleted (16.0%) subgroups. The difference in proliferative index approached significance when the NS2 subgroup was compared with the NS1 subgroup (p less than or equal to 0.11) and when the lymphocyte depleted and NS2 subgroups combined were compared with the mixed cellularity, lymphocyte predominance, and NS1 subgroups combined (p less than or equal to 0.07). There was a trend towards better survival for patients with aneuploid tumours and those cases with a proliferative index below 15%, but neither of these trends was significant.

Downgrading of Non-Hodgkin’s Lymphoma following Chemotherapy

A case of high-grade non-Hodgkins lymphoma (malignant lymphoma centroblastic) is presented which, following chemotherapy, manifested low-grade histology. The importance of repeated biopsies in cases of persistent or recurrent disease following therapy for lymphoma is emphasized.

Chronic Myeloid Leukaemia in Yorkshire: A Case Control Study

The results of a case-control study of chronic myeloid leukaemia in adults are reported. 122 cases and 241 controls were interviewed. Excess risks associates with heart disease and related drugs were revealed. In addition a weak association with occupational and/or hobby exposure to irradiation emerged.

A new approach to the treatment of advanced high-grade non-Hodgkin's lymphoma — intensive two-phase chemotherapy

SummaryA total of 110 patients with high-grade non-Hodgkins lymphoma (NHL) not previously treated by chemotherapy or by radiotherapy at more than one site of disease underwent a regimen comprising an intensive 6-week initial, induction phase using vincristine, adriamycin, methotrexate, and prednisolone (VAMP) followed by the non-cross-resistant combination cyclophosphamide, etoposide, and vindesine (EEE). The median age of patients was 54 years, the majority having stage IV disease. The median follow-up was 34 months and all patients have completed treatment. The overall complete remission (CR) rate for all patients was 68%. The initial phase of treatment produced a CR rate of 49%. The full regimen was completed by 87 patients, and of these, 66 (76%) achieved CR. Of those achieving CR, 72% were relapse-free, on an actuarial basis, at 2 years. Overall 2-year survival was 53%, with a median survival of 31 months. The survival of older patients and those with lymphoblastic histology was comparable to that of other groups. The survival prospects of patients with stage IV disease was not as good as that of other patients, with a significant trend to shorter survival in patients with more advanced disease. Toxicity was predictable and manageable for both phases of the regimen, although it was more severe for the initial phase. Dose-limiting toxicities were neutropenia and mucositis. This regimen is active in the treatment of advanced high-grade NHL with acceptable toxicity. These results have encouraged us to continue the study of weekly chemotherapy, which we will compare with standard cyclical chemotherapy in a prospective, randomized trial.