A.M. Jelliffe

The Prognostic Significance of Cellular Subtypes in Nodular Sclerosing Hodgkin's Disease: An Analysis of 271 Non-laparotomised Cases (BNLI Report No. 22)

A histological review of 271 cases of nodular sclerosing Hodgkins disease, patients presenting with clinical Stage I, II and III disease but not subjected to a staging laparotomy, has been undertaken. Cases were categorised according to the cytological appearances of the cellular nodules and the degree of sclerosis was examined. Cytological subtypes with extensive and easily recognised areas of lymphocyte depletion or numerous pleomorphic Hodgkins cells were associated with a decreased survival and clinical stage did not appear to be a good indicator of prognosis in these patients. Pronounced nodal sclerosis was associated with a higher relative frequency of mediastinal disease and the lymphocyte-depleted cytological subtypes.

British National Lymphoma Investigation randomised study of MOPP (mustine, Oncovin, procarbazine, prednisolone) against LOPP (Leukeran substituted for mustine) in advanced Hodgkin's disease--long term results.

From 1979-1983, 299 patients with stage III or IV Hodgkins disease (HD) were randomised to receive cyclical chemotherapy with MOPP (mustine, Oncovin, procarbazine, prednisone) or LOPP (Leukeran substituted for mustine). Two hundred and ninety patients were evaluable. There was no statistically significant difference between the complete remission (CR) rates (63% for MOPP, 57% for LOPP), percentage of patients remaining disease free at 5 years (38% for MOPP, 35% for LOPP) and overall survival at 5 years (65% for MOPP, 64% for LOPP). On multivariate analysis younger age, grade I histopathology, absence of systemic symptoms, and normal albumin level were favourable prognostic factors for survival. Acute toxicity in the form of nausea/vomiting, myelosuppression, and phlebitis were less with LOPP than MOPP. Deaths in both groups were usually due to disseminated Hodgkins disease; there were no infective deaths in the absence of Hodgkins disease. Second malignancies occurred in six patients treated with MOPP--three acute myeloid leukaemia (AML), one non-Hodgkins lymphoma (NHL), two carcinomas (Ca); with LOPP, four second malignancies occurred (one AML, one NHL, two Ca). These long term results confirm that LOPP is as effective as MOPP, and less toxic, in the treatment of advanced Hodgkins disease.

Selective peripheral blood eosinophilia associated with survival advantage in Hodgkin's disease (BNLI Report No 31). British National Lymphoma Investigation.

A peripheral blood eosinophilia was found at presentation in 193 of 1260 (15%) patients with Hodgkins disease who had been entered into clinical studies by the British National Lymphoma Investigation (BNLI). Eosinophilia as a component of a general leucocytosis conferred no survival advantage. Eosinophilia without a general leucocytosis was present in 95 patients, and this selective eosinophilia was associated with a clear survival advantage. The association of selective eosinophilia and improved survival was limited to patients with mixed cellularity and grade I nodular sclerosis histology. Selective eosinophilia was found to be a good prognostic indicator both in local and generalised disease. Its survival advantage seemed to lie in the response to second line treatment following relapse.

Laparotomy and splenectomy as routine investigations in the staging of Hodgkin's disease before treatment

The authors report 22 patients with Hodgkins disease in whom laparotomy, splenectomy, abdominal lymph node biopsy and open liver biopsy have been performed during routine investigation. The extent of the disease demonstrated at laparotomy has been compared with the extent of the disease thought to be present before laparotomy, as determined by clinical, radiological, isotopic and biochemical investigations. From this comparison it can be concluded that the lymphogram was a valuable but not infallible investigation. Grossly abnormal lymph nodes demonstrable by X-Ray examination were always confirmed at laparotomy. Of 11 negative lymphograms, only 1 proved to be an incorrect diagnosis. An equivocal lymphogram appeared to be a definite indication for laparotomy. The pre-operative assessment of splenic involvement was difficult. In 10 patients, the post-operative findings confirmed the pre-operative assessment, but in 12 patients the pre-operative findings were contradicted by pathological examination of the removed spleen. It was impossible to demonstrate or exclude early infiltration of the liver using currently available methods of investigation. The authors conclude that in the near future, laparotomy, splenectomy, abdominal lymph node biopsy and liver biopsy will be generally accepted as an essential routine investigation, when attempting to cure patients with Hodgkins disease with radical radio-therapy.

The value of staging bone marrow trephine biopsy in Hodgkin's Disease

A retrospective study of pre‐treatment bone marrow biopsies was undertaken to examine the value of bone marrow staging in Hodgkins Disease. Bone marrow biopsy revealed infiltration in 40 out of 613 cases, (6.5%). These patients were not significantly different from stage 4 patients without marrow involvement with regard to age, sex, anaemia or survival. Peripheral blood lymphopenia and lymphocyte depleted histopathological type were more common in patients with marrow involvement. Bone marrow biopsy altered individual patient management in less than 1% of 613 patients and can no longer be recommended as part of the routine staging in Hodgkins Disease

Localised grade 2 non-Hodgkin's lymphoma: Results of treatment with radiotherapy (BNLI report no. 24)

This report reviews 85 patients entered into the British National Lymphoma Investigation with localised (clinical Stage 1 and 2) Grade 2 non-Hodgkins lymphoma, who were treated initially with radiotherapy alone. Almost half of all patients presented with extranodal disease. The duration of follow-up was 20-106 months. There were 33 deaths due to non-Hodgkins lymphoma. The complete local response rate was dependent on the radiotherapy dose and reached 100% for doses of 4500 cGy or more. Most first failures occurred at a distant nodal site or were due to the development of generalised disease. There was a significant difference in actuarial survival between Stage 1 and Stage 2 patients (P less than 0.005). The 5-year survivals were 78% and 40%, respectively. The site of presenting disease was also important. Stage 1 patients with nodal or ear, nose and throat (ENT) disease had an excellent 5-year survival of 84%, but Stage 2 patients with nodal or ENT disease had a 5-year survival of only 46%. As many of these Stage 2 patients rapidly developed disseminated disease, their survival might have been improved by treatment with chemotherapy before radiotherapy.

The present place of radiotherapy in the cure of Hodgkin's disease

Summary (1) The author reviews 300 patients with Hodgkins Disease seen at the Middlesex Hospital between 1930 and 1954. One half had Stage I or II disease and in this group 39% survived 10 years, or longer. (2) Adequate radiotherapy (2,500 r in 12 days—4,000 r in 28 days, 180 to 250 K.V. x-rays) can produce cure of the disease in the irradiated volume, and it appears that more patients would be cured if ‘prophylactic’ irradiation was used in selected cases. (3) There is no place for pessimistic procrastination or for therapeutic half-measures in the treatment of potentially curable Hodgkins Disease.

The Pathological Findings Following Laparotomy in Hodgkin's Disease

The pathological findings in 50 patients with Hodgkins disease following laparotomy for diagnostic purposes are described. Forty-four patients had laparotomy before treatment and within a few months of the original diagnosis, while 6 patients had delayed laparotomies. The Rye histological classification was applied to the original lymph node biopsy, the abdominal lymph node and Hodgkins tissue in the spleen. The variation in appearance both of these tissues and of the liver biopsies is discussed.

The evolution of the British National Lymphoma Investigation (report no 5)

This report reviews the evolution of the British National Lymphoma Investigation since its inception in 1970. With the collaboration of colleagues from 35 centres, pathological material from more than 4500 patients has been referred to the Pathology Panel and almost 3000 cases have been included in a number of prospective trials of treatment methods in Hodgkins disease and the non-Hodgkins lymphomas. Reference is made to general principles adhered to by the group and to the collection of clinical and pathological material by which these studies have been made possible.

The diagnosis of Hodgkin's disease in surgically excised spleens

A series of 44 spleens removed from patients with Hodgkins disease before treatment has been reviewed. The difficulties encountered in detecting foci of Hodgkins tissue and the histological features and characteristics of early invasion are described.