Clinical course of metastatic parathyroid cancer.

In a retrospective study the clinical course of 40 patients with symptomatic persistent or recurrent parathyroid cancer was analyzed in order to assess the value of aggressive surgical intervention. Recurrence was diagnosed after a median period of 33 months (1-228 months). Twenty-two patients had locoregional disease, whereas 14 patients had both local and distant spread. The remaining four patients had distant spread. Patients with just locoregional disease were subject to one to nine reoperative procedures. The median survival time from the last operation was 39 months (1-204 months). Eight patients then had no evidence of disease, three were hypercalcemic and 9 of 11 had died of parathyroid cancer. Distant spread was demonstrated in 17 of 40 patients. Pulmonary metastases predominated (14 of 17). Surgical excision was performed in 9 of 14 cases. Of these nine, two patients had a subsequent disease-free interval of 36+ and 72+ months, respectively. One patient was reported hypercalcemic after 84 months, whereas five patients died of cancer between 4 and 60 months after their last surgical exploration. One patient was lost to follow-up. In all, 21 patients (53%) died of parathyroid cancer. Conspicuous nuclear atypia and frequent mitoses predominated. Image cytometric DNA analysis showed high rates for all three groups (median p90 = 80%, range 21-98%).

Increased serum CD8 soluble antigen level is associated with blood lymphocyte abnormalities and other established indicators of a poor prognosis in adult Hodgkin's disease.

Measurement of the soluble form of CD8 antigen (sCD8), a surface membrane component of suppressor/cytotoxic T cells, has yielded useful information relevant to prognosis in children with acute lymphoblastic leukaemia and Hodgkin's disease (HD). An ELISA technique was used to measure the amount of sCD8 in sera from 123 adults with untreated HD. Significantly higher mean sCD8 levels were found in patients with advanced disease (stage III-IV; P less than 0.001), B-symptoms (P less than 0.001), male sex (P less than 0.05) and increased spontaneous and decreased Concanavalin A induced blood lymphocyte DNA-synthesis (P less than 0.05). Actuarial survival of patients with high sCD8 levels was significantly worse than that of the remainder (P less than 0.05). However, the sCD8 level did not add prognostic information to that achieved by age, sex, lactate dehydrogenase (LDH) or clinical stage. A significant correlation between the sCD8 and LDH levels (r = 0.33; P less than 0.001) and inverse correlations between sCD8 levels and total blood CD4+ (r = -0.52; P less than 0.001) and CD3+ (r = -0.39; P less than 0.01) cell counts were found. Ten patients were also studied in complete remission, showing a significantly reduced sCD8 level in comparison to the pretreatment value (P less than 0.05). Increased sCD8 in HD may indicate enhanced suppressor T cell activity possibly compromising the host disease balance which could explain the association with prognosis.

Increased luminol-enhanced chemiluminescence of blood monocytes and granulocytes in Hodgkin's disease.

The oxidative metabolic burst of blood monocytes and polymorphonuclear leukocytes (PMN) from 22 untreated patients with Hodgkin's disease (HD) and 18 healthy subjects were studied. Monocytes and PMN were enriched by density centrifugation and in vitro activated by zymosan. The oxidative metabolism was measured by luminol-enhanced chemiluminescence (CL). The CL of the patients' monocytes and PMN was higher than that of controls (P less than 0.01 and P less than 0.05, respectively). Patients with stage II-IV HD showed an increased blood monocyte CL as compared with stage I patients (P less than 0.05). Furthermore, patients with lymphocytic depletion or mixed cellularity subtype demonstrated an increased CL of PMN as compared with the remainder. Enhanced CL of phagocytes has been observed in chronic inflammatory disease and can be induced by various serum factors such as monokines and immune complexes. The present study demonstrates an increased CL of blood-borne phagocytic cells in untreated HD. Furthermore, CL of blood monocytes and PMN correlated to tumour burden and histologic subtype, respectively.

Surface markers and cytotoxic activity of blood natural killer cells studied at the single cell level in Hodgkin's disease.

Purified peripheral blood lymphocytes (PBL) from nine untreated patients with Hodgkin's disease (HD), two HD patients in complete remission and 17 healthy donors were studied for natural killer (NK) cell activity against the K-562 cell line using a single cell cytotoxic assay, which allowed enumeration of effector cells and characterization of their surface membrane phenotypes after staining with monoclonal antibodies. The frequency of NK cells was significantly lower in HD patients than in controls (mean % +/- s.d., 1.9 +/- 0.9 and 2.8 +/- 1.2, respectively), while the fraction of target binding cells was similar in the two groups. The fraction of cytotoxic lymphocytes increased after pre-treatment of PBL with 500 iu leucocyte interferon in all tested control donors (n = 12) and the two patients in remission but only in four of seven untreated patients. No relation between the impaired NK cell frequency and age, tumour histology and clinical stage could be revealed. Subtyping of the target cell binding NK cells by monoclonal antibodies disclosed a marked heterogeneity of effector cells. NK effector cells reactive with M1 and anti-Ia antibodies were enriched while T3+ and T4+ NK lymphocytes tended to be reduced as compared to PBL. There was no difference between patients and healthy donors with regard to the surface antigen patterns of NK cells. Interferon treatment did not alter significantly the phenotypic characteristics of cytotoxic lymphocytes in patients and controls. It is concluded that the impairment of NK cell activity in HD is partly attributed to a lower frequency of cytotoxic effector cells among a normal number of target binding cells. The defect could not be attributed to a selective defect of effector cell subsets.

Immune deficiency in family members of patients with Hodgkin's disease.

Indirect data supporting a preexisting immunologic impairment in patients with Hodgkin's disease (HD) have been presented in recent years. These immunologic defects are supposed to be related to genetic and/or environmental factors. In this study, 65 first-degree relatives and 12 spouses of 21 consecutive patients with HD were studied immunologically. Furthermore, seven twin pairs in which one partner had HD and four additional nonmatched healthy co-twins were also included in the study. A decreased lymphocyte DNA synthesis induced by Concanavalin A, a high spontaneous DNA synthesis, or a low CD4+/8+ ratio was found in 21 (32%) consanguineous, two (17%) nonconsanguineous relatives, and five (50%) healthy co-twins. The corresponding figures for the untreated patients with HD and the control series were 14 of 21 (65%) and 21 of 127 (16%), respectively. Total lymphocyte counts or lymphocyte subpopulations did not differ between HD relatives and controls. The increased frequency of blood lymphocyte defects among consanguineous first-degree relatives favors the existence of a genetically determined immune deficiency in at least a proportion of apparently healthy relatives of patients with HD. However, nongenetic factors such as age and environment may add to the defect.

Increased blood clearance rate of indium-111 oxine-labeled autologous CD4+ blood cells in untreated patients with Hodgkin's disease.

Untreated patients with Hodgkin's disease (HD) have a blood T-lymphocytopenia mainly caused by a reduction of the CD4+ subset. Indirect support for a sequestration of T cells in the spleen and tumor-involved lymphoid tissue has accumulated. To test the hypothesis that the blood CD4 T-lymphocytopenia in patients with HD is caused by an altered lymphocyte traffic, 12 untreated HD patients and five in complete clinical remission (CCR) were studied. Blood lymphocytes were collected by leukapheresis and gradient centrifugation, and were further purified by an adherence step. The cells were labeled with indium-111 oxine and reinfused intravenously into the patient. The radioactivity of CD4+ and CD8+ blood lymphocytes separated by immunoabsorption was measured from serial blood samples. CD4+ cells were eliminated more rapidly in untreated patients than patients in CCR. Repeated gamma camera imaging after autotransfusion of indium-111 oxine labeled cells demonstrated an accumulation of radioactivity in tumor-involved tissue of untreated patients. These findings support the concept of an enhanced elimination of CD4+ cells in patients with active HD that may contribute to the observed blood T-lymphocytopenia and may reflect a biologic response to the tumor.

Lymphocyte abnormalities predicting a poor prognosis in Hodgkin's disease. A long-term follow-up.

Two hundred sixty-two adult patients with Hodgkin's disease (HD) were studied. Incorporation of carbon-14-thymidine was measured in unstimulated monocyte-depleted lymphocyte cultures, and in cultures activated by concanavalin A (Con-A) before institution of therapy in all patients. Total blood lymphocytes and T-cell subsets were enumerated in the last 108 patients. Patients had significantly decreased total (CD3+, CD4+, CD8+) and relative (CD3+, CD4+) T-cell counts compared with healthy controls. Stage IV patients tended to have lower total lymphocyte and subset counts than remaining patients. However, significantly reduced total lymphocyte and CD8+ counts were only observed in comparison to patients in clinical stage II. Thirty-three percent of patients had an increased spontaneous and a decreased Con-A-induced blood lymphocyte DNA synthesis. Functional lymphocyte abnormalities were related to advanced clinical stage, high age, mixed cellularity, and lymphocyte depletion histopathology and presence of B symptoms. The 10-year survival of patients in this group was 36%, compared with 62% for the remainder. In a multivariate analysis of the whole series lymphocyte DNA synthesis was besides age the strongest predictor of prognosis. In univariate analyses of the second patient series total lymphocyte, T-cell and subset counts were related to prognosis. These relatively simple lymphocyte functional tests may help to identify young HD patients for whom intensive cytoreductive therapy with or without autologous stem cell support may be the best therapeutic option.