Impaired generation of helper T cells in a patient with chronic mucocutaneous candidiasis and malignant thymoma.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to R E Ritts.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Immunological data were obtained during the course of a randomized trial comparing intrapleural BCG plus oral isoniazid (INH) with intrapleural saline plus oral placebo after resection of stage I non-small cell lung cancer. Immunological testing with a variety of assays was carried out with good standardization among six collaborating laboratories and with good reproducibility within each laboratory. Those patients with larger tumors tended to have higher initial white cell counts. The percentage of lymphocytes in the differential was greatest in those with non-squamous cancer histology. Otherwise, no associations were found between initial immunologic parameters and baseline variables. The main effect of BCG/INH therapy was to cause statistically significant increases in purified protein derivative (PPD) skin test induration and PPD in vitro blastogenesis compared with controls. Other skin tests and in vitro assays increased more in the saline/placebo control group, but these treatment differences were usually not statistically significant. Initial white count and neutrophil count elevations were found to be associated with increased risk of recurrence. Even after adjustment for treatment and tumor stage, initial neutrophil count elevation was associated with increased risk of recurrence. Surprisingly, a low 29 degrees C T cell rosette index was associated with a decreased risk of recurrence, though the differences were minimal. Serial immunological tests were carried out to evaluate their potential for monitoring disease recurrence. White count elevations continued to be significantly associated with increased risk of recurrence, but more follow-up data are needed before other associations can be assessed.
Forty-four patients with unresectable primary, residual, or recurrent colorectal carcinoma confined to the pelvis were randomized to treatment with split course megavoltage radiotherapy alone (5,000 rad given over 7 weeks) or in combination with the intradermal administration of the methanol extraction residue of BCG (MER) over an eight-month period. No improvement was observed in frequency of symptomatic palliation, interval to progression, or survival among patients receiving MER. Furthermore, there was no evidence of enhanced immunological status in patients receiving MER as compared to those receiving radiation alone. Although temporary pain relief was seen in 94% of patients with pretreatment pelvic or perineal pain, 37 patients (84%) have experienced subsequent progressive malignant disease. Regional recurrences within the radiotherapy port were observed in 28 of 31 patients who were evaluable for analysis of pattern of sites of initial progression. Eleven of the 28 patients with local failure also had distant metastasis at the time of tumor progression. There was no discernible clinical value associated with MER treatment in combination with radiotherapy as employed in this study. The high frequency of pelvic recurrence following radiotherapy at the dose and schedule we employed highlights the need for more effective treatment strategies for this group of patients.
Explore the source record for details and available documents.
One hundred thirty adult patients with metastatic solid tumors were studied to evaluate the therapeutic results, toxicity, and immunological effects of three BCG preparations given intradermally by the multiple puncture time technique on either a monthly or weekly schedule: Tice lyophilized BCG, Pasteur lyophilized BCG, and Pasteur fresh-frozen BCG. Patients were randomly assigned in a double-blind manner to receive one of the BCG preparations or saline placebo administered in an identical manner. A battery of immunological tests were performed pretreatment and serially during the investigation. None of the 82 patients with measurable indicator lesions experienced an objective tumor response, nor were there any differences in survival among patients receiving any of the BCG preparations compared to placebo. Toxicity consisted of mild to moderate local cutaneous reactions and liver function abnormalities in BCG-treated patients with no significant differences between BCG preparations. Improvements in each of the assays of immune function performed occurred with roughly equal frequency among patients receiving BCG or placebo. It was not possible to demonstrate any significant clinical or immunological benefit from BCG administration in this patient population with the methodology employed.
Explore the source record for details and available documents.
Assays of immune function (recall skin tests to microbial antigens; total circulating lymphocytes, T-cells, B-cells; lymphocyte blastogenesis with PHA, Con A, and pokeweed mitogens; and serum immunoglobulins IgA, IgM, IgG) were obtained in 408 patients with unresectable gastrointestinal carcinoma. The overall patient population, in comparison to normal controls, was characterized by reduced response to recall skin tests, reduced total lymphocyte and T-cell counts, reduced lymphocyte blastogenesis assays, increased B-cell counts and increased IgA and IgM. Significant immunosuppression was associated with prior radiation or chemotherapy, and with impaired patient performance status. There was no apparent correlation between extent of clinically evident malignant disease and immune function within this patient population. No assay of immune function matched the prognostic value of the more readily available and less expensive determinations of performance status, serum alkaline phosphatase, or SGOT. Only reactivity to recall skin tests had a significant correlation to patient survival independent of performance status. Among patients with little or no disability, only intensity of skin test reactivity correlated significantly with survival; and among those with greater disability, there was correlation only with proportion of skin tests positive. The combination of candida and streptokinase antigens provided the best recall skin test survival correlation. Adding a third, fourth, or fifth antigen did not add to prognostic value. From an overall standpoint, the immune determinants which we studied do not appear to provide useful additions to the evaluation of the patient with unresectable gastrointestinal cancer.
Tumor necrosis in situ by cryosurgery, electrocoagulation, or ligation generally induces or augments some increase in tumor-specific transplantation immunity (TSTI) as compared with excision. Excision of the tumor 24 hours after it has been rendered ischemic by either ligation or cryosurgery seems to produce TSTI that is significantly greater than that after excision of viable tumor without prior ligation or cryosurgery; the degree of this immunity is similar to that seen after the tumor is left in situ indefinitely after treatment. These data suggest that most of the immunization following tumor necrosis in situ occurs within 24 hours of treatment. The experimental findings support the clinical reports of putative immunologic potentiation after tumor necrosis in situ.
Thirty children with previously untreated acute lymphoblastic leukemia were studied prior to therapy to determine whether sheep erythrocyte (E)-receptor status correlated with clinical factors, cytochemical staining characteristics, FAB morphologic classification, and karyotype. Five patients (17%) with more than 50% E+ blasts had intense focal acid phosphatase staining and distinct clinical characteristics, including high leukocyte counts, mediastinal masses, and involvement of the central nervous system at diagnosis. Focal acid phosphatase activity was present in blasts of patients with greater than 20% E+ blasts, but this group had fewer poor risk factors. Morphologic and karyotypic features were not related to erythrocyte-receptor status, but the L2 morphologic appearance occurred more frequently in older patients (P less than 0.05). Erythrocyte receptors have both qualitative and quantitative clinical correlations in childhood acute lymphoblastic leukemia; however, E+ and E- groups are heterogeneous and E+ groups must be analyzed for other risk factors and relapse rates determined before firm conclusions can be made about erythrocyte rosetting as an independent risk variable.
Eighty-four patients with advanced cancer refractory to conventional therapeutic modalities were randomly assigned in double-blind fashion to one of three intradermal treatment regimens: "high"-dose methanol extraction residue fraction of Bacillus Calmette-Guérin (MER) (2.0 mg); "low"-dose MER (0.5 mg); or 0.9% NaCl solution placebo. Toxicity, consisting primarily of cutaneous inflammation and ulceration, was limited to patients receiving MER and was most severe with the high-dose regimen. Pretreatment clinical and immunological parameters were comparable between patient groups. Although a significant number of patients had increases in various immune parameters according to the criteria used, there was no appearent advantage to MER given in either dosage schedule compared to placebo. Patient survival was not affected by either MER regimen compared to placebo. This investigation failed to demonstrate any significant clinical or immunological benefit from MER given in two dosage regimens in patients with advanced cancer with the laboratory methodology used and emphasizes the importance of appropriate controls in evaluating immunostimulants in humans.
Explore the source record for details and available documents.
Fifty-four patients from the surgical gastroenterology service and 22 healthy controls have been prospectively evaluated in a single-blind protocol by the LAI tube method. The LAI correctly identified 25 of 33 early colorectal patients staged as Dukes' B and C at surgery but none of the Dukes' D patients. An inverse relationship was seen between the results of the non-adherence index (NAI) and CEA levels which was most pronounced in those with advanced colorectal cancer. The majority of Dukes' B and C patients having a "false negative" LAI had a CEA level greater than 2.5 ng/ml, suggesting that more advanced disease than that seen at surgery may be present. Two of 22 normal controls gave a borderline positive NAI. Some technical problems, including the relatively short life of the tumor extracts, are discussed.
The clinical findings in 262 patients with melanoma were correlated with an assessment of their cellular-mediated immunity by delayed-type hypersensitivity (DTH) skin tests, by lymphocyte blastogenesis, and by leukocyte enumerations. Patients with systemic metastases (stage IV) and those with evidence of tumor burden had fewer positive DTH reactions for recall antigens than did patients with localized disease (stage I), patients with no evidence of tumor burden, and 227 normal controls. However, no differences were found in the magnitude of response among patients with melanoma or when compared with controls. Patients with melanoma had fewer responses to dinitrochlorobenzene (40% than did controls (98%), but there were no differences by stage or tumor burden. Similarly, blastogenesis in the presence of PHA, Con A, and PWM was depressed when compared with controls, but there was no meaningful correlation with the clinical status. Leukocyte, T cell, or B cell counts revealed no alteration from normal for the patients with melanoma. The usefulness of these studies for routine clinical monitoring is questioned.
Explore the source record for details and available documents.
A randomized study compared the effects of combination chemotherapy (high-dose methotrexate, adriamycin, and vincristine) with immunotherapy in the form of transfer factor in the adjuvant treatment of patients with nonmetastatic osteogenic sarcoma after apparent complete surgical ablation of the primary tumor. Thirty-two patients were evaluated. Of 22 patients who received chemotherapy, three died of drug-related complications and six were alive without disease recurrence between 260 and 673 days after operation. Ten patients in the transfer factor group converted their markers, and of these, five were alive without recurrence 420--753 days after operation. Neither treatment program was considered superior with respect to disease-free survival.
Several measurements indicate that cellular and humoral immunity is depressed in patients with sarcoma; but whether such observations reflect diminished numbers of lymphocytes and their subpopulations is not known. We determined the numbers of peripheral leukocytes, lymphocytes, rosette-forming thymus-dependent cells (T cells), and nonthymus-dependent SmIg-bearing cells in 134 patients with various mesenchymal sarcoma and in 47 normal controls. In all of these determinations, patients and controls gave similar values. Furthermore, values for patients with or without tumor, with or without metastasis, and with bone or soft-tissue sarcomas were similar. All 134 patients were studied prospectively, and the 84 who remained free of disease after 6 months had virtually identical values to the 50 who showed disease progression.
Experiments were designed to assess 1) relative immunity after adoptive transfer of spleen cells or serum from tumor-bearing mice to untreated syngeneic mice, and 2) the degree of tumor-specific transplantation immunity imparted by cells or serum relative to tumor size and the presence of metastases in the donor at the time of spleen cell or serum transfer or after in situ necrosis of the primary tumor by cryosurgery in a CDF1-sarcoma system. Viable lymphoid spleen cells or serum from normal mice had no effect on tumor growth. Serum from mice that had large tumors and gross metastases induced a protective effect similar to that found after cryosurgery of the primary tumor. Serum from mice with small tumors and spleen cells from animals bearing either small or large tumors failed to induce immunity consistently. In no instance did serum from tumor-bearing mice induce enhancement of tumor growth.