The evolution of our concepts concerning the fundamental nature and natural history of Hodgkin's disease is reviewed. Recent evidence establishes that it is indeed a malignant neoplasm, albeit a curious one, the giant cells of which display aneuploid karyotypes, often with marker chromosomes indicating their clonal derivation, and the functional and surface marker properties of cells of the mononuclear phagocyte series. The disease tends initially to spread by contiguity from one lymph node chain to others with which direct lymphatic channel communications exist. Essentially all patients, even those with limited disease, have some degree of impairment of cell-mediated immunity, apparently due to inhibition of T-lymphocyte function. Lymphangiography, computed tomography, and laparotomy with splenectomy have greatly improved the accuracy of clinical staging. Total lymphoid megavoltage radiotherapy and/or multidrug combination chemotherapy now permit the eradication of disease of all stages, resulting in a dramatic improvement in prognosis and an increasing frequency of permanent cure of this once inevitably fatal condition.

Hodgkin's disease: unfolding concepts concerning its nature, management and prognosis.

Many features of Hodgkin's disease (HD) among adolescents and young adults suggest that it has an infectious etiology However, the proposal that HD is a contagious disease which can be transmitted by patients or their close contacts has not been substantiated An alternative infectious disease model is suggested by analogy with paralytic poliomyelitis (PP) For both diseases, the peak age of incidence is delayed as living conditions improve For both, increased risk is associated with higher social class and small family size Like PP, HD may be a rare manifestation of a common infection with the probability of disease development increasing as age at infection is delayed This analogy is supported by the report that the risk of HD is higher for persons who had a low frequency of childhood infectious diseases If this model is valid, HD patients represent no hazard to their contacts However, the incidence of HD among young adults may increase in the coming decade because of the current high standard of living and small family size

Epidemiology of hodgkin's disease in the young.

Understanding the components of the immune system that contribute to host defense against infection is key to recognizing infections that are more likely to occur in an immunocompromised patient. In this review, we discuss the integrated system of physical barriers and of innate and adaptive immunity that contributes to host defense. Specific defects in the components of this system that predispose to particular infections are presented. This is followed by a review of primary immunodeficiency diseases and secondary immunodeficiencies, the latter of which develop because of a specific illness or condition or are treatment-related. The effects of treatment for neoplasia, autoimmune diseases, solid organ and stem cell transplants on host defenses are reviewed and associated with susceptibility to particular infections. In conclusion, an approach to laboratory screening for a suspected immunodeficiency is presented. Knowledge of which host defects predispose to specific infections allows clinicians to prevent, diagnose, and manage infections in their immunocompromised patients most effectively.

Overview of Infections in the Immunocompromised Host.

Immunologic studies were done on 47 long-term survivors of Hodgkin's disease who had been treated with MOPP chemotherapy (mechlorethamine, vincristine, procarbazine, and prednisone). Perce...

Persistent immunologic abnormalities in long-term survivors of advanced Hodgkin's disease.

Between July 1968 and July 1986, 915 patients with clinical stage (CS) I and II Hodgkin's disease limited to sites above the diaphragm underwent laparotomy and splenectomy at Stanford University. Fifteen percent were CS I, of whom 76% had cervical/supraclavicular disease, 13% axillary disease, and 9% mediastinal presentations. CS I patients were more likely to be male, were significantly older, and were significantly less likely to have nodular sclerosis (NS) histology than CS II patients. Twenty percent of CS I patients and 30% of CS II patients were pathologically upstaged. No CS I patients were upstaged to pathological stage (PS) IV. Univariate and multivariate analyses of presenting clinical characteristics were performed to predict staging laparotomy findings. CS I women, CS I patients with mediastinal-only disease, and CS I men with either lymphocyte predominance or interfollicular histologies were at low risk for having disease below the diaphragm (5%) or requiring chemotherapy (0%). CS II women wh...

Prognostic indicators of laparotomy findings in clinical stage I-II supradiaphragmatic Hodgkin's disease.

The study comprises 38 unselected and untreated patients with Hodgkin’s disease (HD) and 23 healthy persons. Highly purified blood lymphocytes were analyzed for cells forming rosettes with sheep red blood cells (T lymphocytes), and lymphocytes bearing surface immunoglobulin (B lymphocytes) and/or carrying receptors for complement. Their DNA synthesis, spontaneously, or after activation with mitogens (phytohemagglutinin, concanavallin A, poke weed mitogen) and purified protein derivative (PPD) was measured. Delayed skin hypersensitivity to PPD and mumps antigen was studied. Most HD patients had low numbers of T lymphocytes (50% of the cases below normal range) while the mean B-lymphocyte level was normal but with a greater variation than in the control group. Lymphocytes from most patients were poorly stimulated by T-cell mitogens. Two-thirds of the patients and one healthy control had negative skin reaction to 2 TU PPD and the DNA synthesis of their lymphocytes after activation with PPD was low. Large lymphoid cells (> 9-mm diameter) were commonly present in HD blood and the spontaneous DNA synthesis was high, particularly in lymphocytes from stage B patients. The percentage of T lymphocytes and the stimulation of lymphocytes by T-cell mitogens or by PPD, a T-lymphocyte function, did not correlate and each test only detected defects in about half the cases. Simultaneous application of all tests revealed abnormalities of blood T lymphocytes in 33 out of 38 patients. Although the defects were usually more pronounced in patients with advanced disease, the impairment of T lymphocytes and their functions is present in all stages of Hodgkin’s disease. Cancer 37:751-762, 1976. ATIENTS WITH HODGKIN’S DISEASE (HD) P have altered immunologic functions;l5 delayed hypersensitivity and ability to reject homografts are impaired and they are susceptible to infections caused by fungi, viruses, and rnycoba~terias.~ JJ~~~~ However, humoral immunity is usually normal in early stages of the disease.17J1.27 Lymphocytopenia is a common finding in HD patients, particularly in advanced stage^.^ Thymus-derived (T) lymphocytes in peripheral blood are often 10~,5~36

Lymphocyte abnormalities in untreated patients with Hodgkin's disease.

Purified blood lymphocytes from 81 consecutive and previously untreated patients with Hodgkin's disease were studied in vitro The patients were evaluated 23 to 52 months after institution of therapy and were divided into two prognostic groups: 1 Complete remission with or without previous relapse/relapses 2 Uncontrolled relapse or decreased from Hodgkin's disease Lymphocyte activation by concanavalin A, pokeweed mitogen or phytohaemagglutinin was impaired and spontaneous DNA synthesis was high in patients with poor prognosis as compared to the good prognosis group The prognostic information increased if the four lymphocyte tests were combined in a score (range 0-8) All 8 patients with pronounced lymphocyte defects (score 7-8), died, while all patients with score 0 and 1 were in complete remission In contrast, total lymphocyte and T-lymphocyte counts and lymphocyte stimulation by PPD were of no prognostic value The ability of certain lymphocyte functions to predict prognosis was equal or better than that of age and better than clinical staging, histopathology and symptoms

Prognostic factors in Hodgkin's disease. II. Role of the lymphocyte defect.

Purified blood lymphocytes from 81 consecutive and previously untreated patients with Hodgkin's disease were studied in vitro. The patients were evaluated 23 to 52 months after institution of therapy and were divided into two prognostic groups: 1. Complete remission with or without previous relapse/relapses. 2. Uncontrolled relapse or deceased from Hodgkin's disease.



Lymphocyte activation by concanavalin A, pokeweed mitogen or phytohaemagglutinin was impaired and spontaneous DNA synthesis was high in patients with poor prognosis as compared to the good prognosis group. The prognostic information increased if the four lymphocyte tests were combined in a score (range 0–8). All 8 patients with pronounced lymphocyte defects (score 7–8), died, while all patients with score 0 and 1 were in complete remission. In contrast, total lymphocyte and T-lym-phocyte counts and lymphocyte stimulation by PPD were of no prognostic value. The ability of certain lymphocyte functions to predict prognosis was equal or better than that of age and better than clinical staging, histopathology and symptoms.

Prognostic factors in Hodgkin's disease. I. Analysis of histopathology, stage distribution and results of therapy.

Sera from unselected and untreated patients with Hodgkin's disease (HD) were examined for antibodies to Epstein-Barr viral (EBV) capsid antigens (VCA). Delayed cutaneous hypersensitivity reactions were carried out with purified tuberculoprotein (PPD). Highly purified blood lymphocytes of the same patients were studied morphologically and classified for cell surface markers. Incorporation of 14C-thymidine was used as a measure of spontaneous DNA synthesis and DNA synthesis after exposure to different concentrations of three mitogens (PHA, Conconavalin A and pokeweed mitogen) and PPD. The distribution of EBV titres was in good agreement with previous reports. Most patients were lymphopenic, due to subnormal levels of T lymphocytes. The lymphocyte stimulation and skin tests showed different degrees of impairment in a considerable number of the patients. The results in 43 patients indicated that a relation exists between the immune defect and the anti-VCA titres. High serological anti-VCA reactivity was related to a poor cutaneous response to PPD, a decreased level of T lymphocytes in the blood and a depression of mitogen-induced DNA synthesis.

Epstein-Barr virus (EBV)-associated antibody patterns in relation to the deficiency of cell-mediated immunity in patients with Hodgkin's disease.

A randomized trial is reported which evaluates the effect of early diagnostic splenectomy on the prognosis of patients with Hodgkin's disease (HD) and uncertain prognosis. This was started in January 1973 and concluded in April 1979. Sixty-seven patients were entered in the study and 31 were randomized for splenectomy. All patients except 2 received total nodal irradiation, excluding the splenic and hepatic areas. After 40 months' observation there was no difference between the groups in respect of survival and the number of recurrences. However, relapses occurred earlier in the splenectomized patients. Pneumococcal septicaemia was recorded in 2 splenectomized patients. It is concluded that prognosis is not improved by diagnostic splenectomy in HD patients with uncertain prognosis and treated with total nodal irradiation.

Prognostic effect of early diagnostic splenectomy in Hodgkin's disease: a randomized trial.

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