Observations on Abnormal Cells in the Peripheral Blood and Spleen in Hodgkin's Disease

The occurrence of abnormal cells in the peripheral blood of patients with Hodgkin''s disease has been described in the literature. In the present investigation several varieties of cells were found, two of which are believed to be typical of the disease. The significance of these cells in the peripheral blood is not yet clear, but there seems to be a correlation between the presence of these characteristic cells in the blood and involvement of the spleen by the disease as determined by microscopical examination. In 11 patients both abnormalities proved to be absent; 13 out of 14 other patients showed both the abnormal cells in the blood and Hodgkin lesions in the spleen.If circulating abnormal cells are indeed an indication of the presence of Hodgkin''s disease in the spleen, involvement of this organ is likely to be due to or to give rise to haematogenous dissemination. The other possibility remains that both the occurrence of abnormal cells in the peripheral blood and splenic involvement are due to a multicentric origin of the disease. It seems most unlikely that the splenic lesions are consistent with localized disease still restricted to the lymphoid system. These findings challenge the validity of the present widely used so-called Rye classification of clinical stages in Hodgkin''s disease.     

La laparotomie dans la maladie de Hodgkin: signification de l'atteinte de la rate.

We retrospectively reviewed 224 cases of Hodgkin''s disease, in 120 of which staging laparotomy was performed. The surgical findings in cases of clinical stage I or II disease with supradiaphragmatic presentation or clinical stage III disease did not influence the treatment plans. Of the 64 patients with positive results of laparotomy (splenic or lymph node involvement or both) 51 had splenic involvement; their 5-year survival rate, 57%, was similar to that of the patients with clinical or pathological stage III disease - 58% and 54% respectively. At laparotomy 11 patients with pathological stage III disease were found to have isolated splenic involvement; their 5-year survival rate, 64%, was not appreciably different from that of the patients with clinical stage II disease, 70%; both groups were treated with radiotherapy only. From this study we can conclude that splenic involvement in Hodgkin''s disease has no deleterious effect on survival and that splenic irradiation seems to be as effective as splenectomy in controlling the disease.     

Prednisone in MOPP chemotherapy for Hodgkin's disease.

High remission rates have been produced by MOPP (mustine, vincristine, procarbazine, and prednisone) chemotherapy in patients with advanced Hodgkin''s disease, but the prednisone component has caused adverse effects in patients who have undergone radiotherapy. The remission rates and length of remission were reviewed in 211 patients with Hodgkin''s disease who received chemotherapy either with or without prednisone. In contrast to the findings of a British study, there were no significant differences in remission rates or length of remission between patients who had received prednisone and patients who had not. There were differences between the British prospective study and this retrospective one, but it is difficult to know what accounted for the substantial differences in the findings.     

Combination Chemotherapy in Generalized Hodgkin's Disease

Fifty-two patients with generalized Hodgkin''s disease were treated with a combination of mustine hydrochloride, vinblastine, procarbazine, and prednisolone. Complete remissions were obtained initially in six out of seven patients (86%) who had previously received no treatment, in 15 out of 19 (79%) who had had only radiotherapy in the past, and in 9 out of 26 (35%) who had previously been given chemotherapy with or without radiotherapy. Of these 30 patients in whom a complete remission was obtained 22 have been free of any symptoms or signs of disease for periods ranging from 4 to 22 months. The response to treatment was rapid, and toxicity was not a major problem, except in those who had previously been treated with cytotoxic drugs used continuously and not in courses. A comparative trial of radiotherapy and combination therapy in the treatment of Stage III Hodgkin''s disease is strongly recommended.     

Bleomycin in the Reticuloses

Bleomycin alone was used in the treatment of 54 patients with Hodgkin''s disease in its later stages, 17 with generalized lymphosarcoma, 22 with reticulum cell sarcoma, and 7 with mycosis fungoides. The patients had had radiotherapy and full courses of conventional chemotherapy. Bleomycin was given in doses of 30 mg weekly to an average total dosage of 200 mg, though up to 800 mg could be given because of its marrow-sparing properties. Sixteen (29%) of the patients with Hodgkin''s disease remitted, most of them achieving only a partial remission, and similar results were obtained in the other three reticuloses. Bleomycin would seem to have some beneficial action in the late stages of Hodgkin''s disease, though it is less effective than some drug regimens recently introduced. Nevertheless it may be useful when there is diminished bone marrow reserve. It would be a suitable drug to use in combination therapy of these four reticuloses.     

Pyrogen release in vitro by lymphoid tissues from patients with Hodgkin's disease

The mechanism of fever in patients with Hodgkin''s disease was investigated by examining endogenous pyrogen production by blood, spleen, and lymph node cells incubated in vitro. Blood leucocytes from febrile or afebrile patients with Hodgkin''s disease did not produce pyrogen spontaneously. Spleen cells, however, frequently released pyrogen during initial incubations, unlike spleen cells from patients with non-malignant diseases. Pyrogen production occurred from spleens without observed pathologic infiltrates of Hodgkin''s disease. Lymph nodes involved with Hodgkin''s disease produced pyrogen more frequently than did nodes involved with other diseases. Pyrogen production by tissue cells was prolonged, required protein synthesis, and in some cases was due to mononuclear cells; it did not correlate with fever in the patient. These studies demonstrate spontaneous production of endogenous pyrogen in vitro by lymphoid tissue cells from patients with Hodgkin''s disease.     

Radiotherapy in the treatment of Hodgkin's disease.

Eighty-seven untreated patients with localised Hodgkin''s disease seen from 1969 to 1975 were treated by megavoltage radiotherapy. All were followed for at least 33 months. Thirty-three patients were staged clinically and 54 underwent more extensive investigation by lapaortomy and splenectomy. The projected five-year disease-free survival figures for patients staged surgically were 100% for the 17 with stage IA disease, 70% for the 19 with stage IIA disease, and 73% for the 15 with stage IIIA disease. These results were consistently better than those obtained in clinically staged patients. Five patients died, one of them without evidence of Hodgkin''s disease. As irradiation seems to produce excellent disease-free survival in most patients who are staged accurately at diagnosis, caution should be exercised in the routine use of adjuvant chemotherapy until the full risks of such treatment are clear. Combined modality therapy may be appropriate for patients with unfavourable features at presentation.     

La forme scléronodulaire de la maladie de Hodgkin: expérience du CHU de Sherbrooke

Scleronodular type of Hodgkin''s disease: experience at the Centre hospitalier universitaire de SherbrookeThe nodular sclerosis type of Hodgkin''s disease appears to be a distinct clinical entity. However, the incidence, the initial localization of the tumour and the survival of the patients are variable. The present study was carried out on a group of 17 patients, all French Canadians living in the province of Quebec, from a total of 31 with Hodgkin''s disease, an incidence of 55%. There were more males (10) than females (7). The mean age of the group was 37 years, but that of the females was lower than that of the males. The mediastinum was involved at the onset in 47% of the patients. The initial staging (according to the classification of Rye) in 76% of the patients was I or II.Four patients showed disease below the diaphragm. The lungs were infiltrated three times, the spleen six times, and the liver five times. The duration of survival of the 17 patients was twice that of the patients with the three other types of the disease.     

Value of prednisone in combination chemotherapy of stage IV Hodgkin's disease. Report from the British National Lymphoma Investigation.

A combination of mustine, vincristine (Oncovin), procarbazine, and prednisione (MOPP) and the same combination without prednisone (MOP) were compared in the treatment of stage IV Hodgkin''s disease in a prospective randomized trial. The complete remission rates were 80% with MOPP and 44% with MOP; the difference was highly significant. Prednisone seems to be an important component of the MOPP combination in the management of stage IV Hodgkin''s disease.     

MVPP chemotherapy regimen for advanced Hodgkin's disease

During January 1968 to December 1972, 133 patients with advanced Hodgkin''s disease (HD) were admitted to hospital for combination chemotherapy with mustine, vinblastine, procarbazine, and prednisolone (MVPP regimen). Remission rates were 76% among 49 untreated patients and 90% among 42 patients who had relapsed after radiotherapy. The corresponding five-year survival rates were 65% and 86% respectively. Provided the observed yearly mortality (6%) remains unchanged 75% of patients who had previously received no treatment or irradiation and achieved remission are expected to continue in first remission after five years. Forty-two patients had received prior chemotherapy. They had lower remission and five-year survival rates (40% and 33% respectively), and fewer than half of those achieving remission were still in first remission after five years. There were several reasons for the poor prognosis in this group, including advanced-stage disease (stage IVB), age over 40, and achievement of remission.Chemotherapy was administered on an outpatient basis. Haematological toxicity and immediate drug-related side effects were similar to those of other regimens but there was no appreciable neurotoxicity. Most deaths were due to either HD itself or complications of advanced disease. Five malignancies other than HD occurred in patients who had received both single-agent chemotherapy and radiotherapy before MVPP chemotherapy. Two patients developed osteonecrosis of the femoral heads.Combination chemotherapy has a profound effect on the prognosis of advanced HD. The MVPP regimen yields results comparable to those of other regimens but with perhaps less toxicity.     

鼻咽癌患者外周血循环内皮细胞的检测及临床意义分析

目的分析鼻咽癌患者外周血循环内皮细胞（CECs）的水平及临床意义。 方法选取2016年1月至2018年10月期间于陆军军医大学第二附属医院接受单纯放疗或同期放化疗的55名初诊鼻咽癌患者为研究对象,归为鼻咽癌组,并随机选取同期来医院进行体检的50例健康成人为对照组。比较两组外周血CECs水平,并分析鼻咽癌组不同临床病理资料患者的外周血CECs水平,以及治疗前后的外周血CECs水平变化。根据疗效分为完全缓解（CR）组和未完全缓解组（包括部分缓解、疾病稳定和疾病进展）。两组间比较采用两样本t检验;计量资料采用百分比表示,比较采用χ²检验。 结果鼻咽癌组患者治疗前的外周血CECs水平为（21.13±8.33）个/μl,高于对照组的（5.03±2.25）个/μl,差异有统计学意义（t = 13.230,P < 0.01）。鼻咽癌组治疗前的外周血CECs水平T3~T4期（23.23±8.09）?个/μl高于T1~T2期（16.01±5.22）个/μl,差异具有统计学意义（t = 3.290,P < 0.01）;N1~N3期（22.82±8.16）?个/μl高于N0期（15.06± 3.98）个/μl,差异具有统计学意义（t = 3.176,P < 0.01）;M1期（28.30±3.33）?个/μl高于M0期（19.91±8.23）?个/μl,差异具有统计学意义（t = 2.826,P < 0.01）;Ⅲ~Ⅳ期（23.26±7.93）个/μl高于Ⅰ~Ⅱ期（17.93±5.63）?个/μl,差异具有统计学意义（t = 2.726,P < 0.01）。CR组患者治疗前（20.03±8.12）?个/μl、治疗后3个月（12.61±5.33）?个/μl的外周血CECs水平低于未完全缓解组（26.75±3.29）?个/μl、（19.03±2.62）?个/μl,差异具有统计学意义（t = 5.181、5.507,P均< 0.01）。 结论鼻咽癌患者的外周血CECs水平明显升高,与病情进展、放化疗效果有关,可能成为潜在的肿瘤标志物。     

La TEP-TDM dans la maladie de Hodgkin : expérience clermontoise

The aim of this study was to evaluate the standardized uptake value (SUV) of ¹⁸FDG in Hodgkin's disease according to various histopathologic parameters as well as the impact of the examination on stadification and follow-up. A total of 37 patients profited from a pretherapeutic PET-CT. Standardized uptake value was calculated a posteriori. This one is higher in mixed cellularity Hodgkin's disease compared to nodular sclerosing Hodgkin's disease. In addition, the examination involved a change of stage in 35% of the cases compared to the injected CT. The specificity of the PET-CT at the end of the treatment was 96% and its exactitude of 93%, both significantly higher than those found in CT.     

Sensitisation to Hodgkin's disease spleen tissue in patients with malignant lymphoma: follow-up study.

The leucocyte migration responses of patients with malignant lymphoma to an unidentified factor in Hodgkin''s spleen tissue were serially studied and related to clinical progress. Initial sensitisation responses did not correlate with presenting histological or clinical status or with subsequent clinical progress. Enhancement of responses after treatment, however, was associated with good clinical progress. In patients who relapsed, sensitisation to spleen factor diminished, whereas responses were preserved at one year in those in maintained remission. Sensitisation to the splenic factor may be a useful index of response to treatment in patients with malignant lymphoma; diminishing sensitisation may indicate relapse.     

Selection of 3LL tumor subline resistant to natural effector cells concomitantly selected for increased metastatic potency

Summary The numbers of strongly adherent monocytes in the peripheral blood of normal subjects and cancer patients were determined. The method used was to place peripheral blood mononuclear cells in microwells and culture them for 1 week. At the end of that period, adherent macrophages were counted in the Coulter counter after release. Adherent cells per milliliter of blood, per total cells, and per mononuclear cells or monocytes plated were markedly diminished in the peripheral blood mononuclear cells of 44 melanoma, 23 breast cancer, 18 lung cancer, nine colon cancer, and 27 leukemia patients. Median values were 14.8×10⁴ adherent cells per ml peripheral blood for 86 normal subjects, as against 2.5×10⁴ per ml in the peripheral blood of the 125 patients (P<0.001). There was a poor correlation between the adherent cell numbers and the peripheral blood leukocyte counts, but an excellent correlation of the different adherent cell counts with each other. The number of adherent cells in the peripheral blood varied inversely with age in the cancer patients, but not in the normal subjects (r=0.29, P<0.005). When patients under age 50 were compared to the controls, the deficiency of adherent cells was slightly more severe in patients with stage IV lung cancer than in those with stage III lung cancer. In contrast, there was no difference in the degree of deficiency between patients with stage III melanoma and no evident disease and patients with stage IV disseminated metastatic disease. The implications of these results are discussed.     

Risk of second primary cancers after Hodgkin's disease by type of treatment: analysis of 2846 patients in the British National Lymphoma Investigation.

OBJECTIVE--To analyse the risk of second primary cancers during long term follow up of patients with Hodgkin''s disease. DESIGN--Cohort study. SETTING--The British National Lymphoma Investigation (a collaborative group of over 60 participating centres in Britain treating lymphomas). PATIENTS--2846 patients first treated for Hodgkin''s disease during 1970-87, for whom follow up was complete in 99.8%. MAIN OUTCOME MEASURES--Second primary cancers; uniform pathology reviews confirmed the diagnosis of Hodgkin''s disease and of second primary non-Hodgkin''s lymphomas. RESULTS--113 second primary cancers occurred. Relative risk of cancer other than Hodgkin''s disease was 2.7 (95% confidence interval 2.3 to 3.3) compared with the general population, with significant risk of leukaemia (16.0(9.1 to 26.0)); non-Hodgkin''s lymphoma (16.8(9.8 to 26.9)); and cancers of the colon (3.2 (1.4 to 6.2)), lung (3.8 (2.6 to 5.4)), bone (15.1 (1.8 to 54.7)), and thyroid (9.4 (1.1 to 33.9)). Absolute excess risk associated with treatment was greater for solid tumours than for leukaemia and lymphomas. Relative risk of leukaemia increased soon after treatment, reaching a peak after five to nine years. It was increased substantially after chemotherapy (27.9 (12.7 to 52.9)), combined treatment with radiotherapy and chemotherapy (21.5 (7.9 to 46.8)), and relative to number of courses of chemotherapy but was not significantly increased after radiotherapy (2.5 (0.1 to 14.1)). Relative risk of non-Hodgkin''s lymphoma increased in the first five years after treatment and remained high but showed no clear relation with type or extent of treatment. Relative risk of solid tumours was less raised initially but increased throughout follow up and for lung cancer 10 years or more after entry was 8.3 (4.0 to 15.3). The risk of solid tumours increased after treatments including radiotherapy and after chemotherapy alone. The risk after chemotherapy increased significantly with time since first treatment. CONCLUSION--The risk of solid cancer, not of leukaemia, is the major long term hazard of treatment for Hodgkin''s disease, and this seemed to apply after chemotherapy as well as after radiotherapy. These risks of second cancers are important in choice of treatment and in follow up of patients, but they are small compared with the great improvements in survival which have been brought about by modern therapeutic methods for Hodgkin''s disease.     

Kinetics of indium-III labelled lymphocytes in normal subjects and patients with Hodgkin's disease.

The distribution in the body and the circulation in the blood of autologous lymphocytes labelled with indium-III were studied in two normal subjects and two patients with Hodgkin''s disease. Four hours after injection radioactivity was identified in the spleen, liver, and bone marrow. Radioactivity, followed by imaging and whole body scanning, began to appear in the lymph nodes four to 18 hours after injection, and some, though not all, lymph node groups in the body could be readily visualised. There were no differences between the normal subjects and the patients with Hodgkin''s disease. The pattern of clearance of radioactivity from the blood was consistent with a normal circulation between blood and lymphoid tissues of the labelled lymphocytes. Since indium-111 stays firmly attached to the cell, it seems an ideal label for studying lymphocyte kinetics, and the use of this technique may have further clinical application.     

Immunity to Epstein-Barr virus in Hodgkin's disease preceded by infectious mononucleosis

A patient who developed Hodgkin''s disease four years after infectious mononucleosis had elevated serum antibody titres to Epstein-Barr virus and delayed hypersensitivity reactions to membrane antigens prepared from fresh autologous spleen, from spleen cells of another Hodgkin''s patient, and from cell lines known to carry the Epstein-Barr virus genome. Additional studies in more lymphoma patients will be needed to determine the significance of the reactivity against tumour and virus-associated antigens which has been documented in this patient.     

Current Concepts of Cancer Chemotherapy

The most impressive regressions obtained to date with the use of chemotherapy are in metastatic choriocarcinoma of females. In the management of Hodgkin''s disease, leukemia, and lymphoma, chemotherapy is a useful and accepted form of therapy. In many cases radiation and chemotherapy are interdependent. In disseminated carcinomas arising in the lung, ovary or breast, there is less likelihood of significant improvement with the use of chemotherapy, but if the disease is not amenable to radiotherapy, useful palliation can be obtained at times.While newer chemotherapeutic agents for cancer, notably the pyrimidine analogues, have a broader spectrum of antitumor effects than others investigated earlier, they should be regarded as providing a valuable research stimulus in the continued search for more effective and less toxic agents.     

Commentary: assessing the effects of environmental pollution when people know that they have been exposed.

OBJECTIVE: To examine the effectiveness of routine clinic review in detecting relapse after treatment for Hodgkin''s disease. DESIGN: Review of hospital records. SETTING: Regional centre for cancer treatment and research. SUBJECTS: 210 patients with Hodgkin''s disease recruited to a chemotherapy trial protocol between 1984 and the end of 1990 who had achieved a complete or partial remission after treatment. MAIN OUTCOME MEASURES: The number of clinic visits made by patients over the period of observation, the number of relapses occurring during that time, and the route by which relapse was detected. RESULTS: The 210 patients generated 2512 outpatient reviews, and 37 relapses were detected. Thirty relapses (81%) were diagnosed in patients who described symptoms, which in 15 cases had resulted in an earlier appointment being arranged. In only four cases (11%; 95% confidence interval 4% to 25%) was relapse detected as a result of routine physical examination on investigation of a patient who did not have symptoms. CONCLUSIONS: Relapse of Hodgkin''s disease after treatment is usually detected as a result of the investigation of symptoms rather than by routine screening of asymptomatic patients. It is therefore proposed that the frequency of routine follow up visits should be reduced and greater emphasis placed on patient education. This should underline the importance of symptoms and encourage patients to arrange an earlier appointment if these develop.     

Significance of the Changes in the Circulating Lymphoid Cells in Hodgkin's Disease

The lymphoid cell population in the peripheral blood in Hodgkin''s disease differs from normal blood in three ways. Firstly, the number of large lymphoid cells actively synthesizing deoxyribonucleic acid is increased; secondly, the number of medium-sized lymphoid cells with intensely basophilic cytoplasm is increased; and, thirdly, occasional plasma cells are seen. These changes are related to the activity but not to the stage of the disease.Similar changes are found under conditions of known antigenic challenge—that is, in infections, and after immunization, and in rheumatoid arthritis and systemic lupus erythematosus.