PubMed Health⌕ Search

Biomedical subjects

J A Nizze

Publications and source records attributed to J A Nizze.

12 recordsLinked to original sources
PubMed1999

Active specific immunotherapy with polyvalent melanoma cell vaccine for patients with in-transit melanoma metastases.

BACKGROUND: This study was conducted to document the rate, duration, and type of objective response to active specific immunotherapy with a polyvalent melanoma cell vaccine (PMCV) for patients with in-transit melanoma metastases and to identify any acute or chronic toxic effects of PMCV treatment. METHODS: An analysis was conducted of all in-transit melanoma patients seen at the John Wayne Cancer Institute in Santa Monica, California, during the period 1985-1997 who were enrolled in prospective PMCV protocols in the absence of other therapies with possible antitumor activity (n = 54). Clinical response to PMCV was assessed by standard criteria. Survival curves were estimated by the Kaplan-Meier method. Toxicity was graded according to the Eastern Cooperative Oncology Group standard. RESULTS: PMCV produced a 17% (9 of 54 patients) objective response rate with a 13% rate (7 of 54 patients) of complete remission (CR). The median duration of CR was >22 months. Complete response lasting more than 1 year was observed in 4 patients (7.2%); 1 patient remained in remission over 9 years. Median survival was >53 months (i.e., not reached) for responders, 42 months for nonresponders, and 53 months overall. Salvage interventions allowed reinduction with PMCV in 23 of 25 patients, who subsequently remained clinically free of disease for a median of 14 months. Overall toxicity was mild, easily tolerable, and did not significantly change the quality of life. There were no toxic deaths. CONCLUSIONS: PMCV can cause objective complete regression of measurable intransit metastatic melanoma with minimal toxicity, and may prolong patients' median survival.

Cancer Vaccines↗
PubMed1996

Immune response to polyvalent melanoma cell vaccine in AJCC stage III melanoma: an immunologic survival model.

BACKGROUND: Our polyvalent, allogeneic melanoma cell vaccine (MCV) induces immunoglobulin M (IgM) and immunoglobulin G (IgG) class antibodies to a 90-kDa glycoprotein melanoma-associated antigen (MAA). Additionally, MCV induces delayed-type hypersensitivity (DTH) responses that we previously correlated with survival. We hypothesized that early DTH responses to MCV and early humoral responses to the 90-kDa MAA expressed on MCV cells may be predictive of overall survival. We tested this hypothesis by monitoring immunologic profiles in 59 patients with melanoma who were receiving MCV after surgical resection of regional lymph node or soft-tissue metastases. METHODS: Blood was drawn before vaccine administration, biweekly for 6 weeks, and then monthly. DTH to MCV was recorded at 0, 2, 4, and 8 weeks of MCV therapy. Mean antibody titers during the first 6-week interval were calculated. Changes in DTH were calculated as the difference between peak and prevaccine values (delta DTH). RESULTS: At a median follow-up of 75.6 months (range 5-138), univariate analysis assigned prognostic significance to gender (p = 0.046), lymph node involvement (p = 0.024), delta DTH (p = 0.044), mean anti-90-kDa MAA IgG (p = 0.0009), and mean anti-90-kDa MAA IgM (p = 0.0014). In multifactorial analysis, only the three immunologic variables significantly impacted survival (p = 0.046, 0.0005, and 0.0053, respectively). A mathematical model based on delta DTH and mean anti-90-kDa MAA IgG and IgM titers closely approximated the observed individual and overall survival rates. CONCLUSIONS: The correlation between overall survival and initial humoral/cellular immune responses to MCV immunotherapy may be useful in selecting patients most likely to benefit from prolonged adjuvant immunotherapy.

Adolescent↗
PubMed1994

Polyvalent melanoma cell vaccine induces delayed-type hypersensitivity and in vitro cellular immune response.

Patients with melanoma metastatic to distant sites or at high risk for recurrent melanoma have been treated with a polyvalent melanoma cell vaccine (MCV) in phase II protocols. We assessed in vivo and in vitro cell-mediated responses to MCV in 163 patients who had undergone surgical resection of American Joint Committee on Cancer stage III melanoma. During the first 4 months of vaccine immunotherapy, 135 patients (83%) responded by developing a positive delayed-type hypersensitivity reaction > or = 6 mm to MCV. In a mixed lymphocyte tumor cell reaction using peripheral blood lymphocytes, 35 of 42 patients (83%) showed a recall proliferative response to one or more of the three cell lines of MCV. There was a significant correlation between delayed-type hypersensitivity reaction and mixed lymphocyte tumor cell reaction (P = 0.013). After 4 months of MCV therapy, 8 of 11 patients had an increased mixed lymphocyte tumor cell reaction to autologous melanoma cells. During the first 4 months of vaccine therapy, 16 of 33 patients developed more than a 50% increase in cytotoxic T-cell activity against one of the cell lines of MCV. Overall survival was significantly prolonged in patients with a positive delayed-type hypersensitivity reaction (P = 0.0054) and/or increased cytotoxic T-cell activity (P = 0.02). These findings suggest that MCV induces specific T-cell responses which are correlated with clinical course; the data also suggest that some of these responses are directed against autologous melanomas and may play a major role in controlling the progression of melanoma.

Adolescent↗
PubMed1992

Prolongation of survival in metastatic melanoma after active specific immunotherapy with a new polyvalent melanoma vaccine.

A new polyvalent melanoma cell vaccine (MCV) was administered to 136 stage IIIA and IV (American Joint Committee on Cancer) melanoma patients. Induction of cell-mediated and humoral immune responses to common melanoma-associated antigens present on autologous melanoma cells was observed in patients receiving the new MCV. This was accompanied by increased activation of tumor-infiltrating lymphocytes. Survival correlated significantly with delayed cutaneous hypersensitivity (p = 0.0066) and antibody responses to MCV (p = 0.0117). Of 40 patients with evaluable disease, nine (23%) had regressions (three complete). From our historical database of 126 stage IIIA and 1275 stage IV melanoma patients, there were no significant changes in the natural history of metastatic melanoma during the past 20 years. Univariate and multivariate analyses demonstrated prognostic significance for site of metastases (p = 0.0001) and immunotherapy with the new MCV (p = 0.0001). Overall our new MCV increased the median and 5-year survival of stage IIIA melanoma patients with regional soft tissue metastases twofold (p = 0.00024), and stage IV patients threefold (p = 0.0001) compared with previous immunotherapy and other treatments.

Adult↗
PubMed1991

Improved long-term survival after lymphadenectomy of melanoma metastatic to regional nodes. Analysis of prognostic factors in 1134 patients from the John Wayne Cancer Clinic.

A review of 1134 patients from the John Wayne Cancer Clinic with melanoma metastatic to regional lymph nodes was carried out to evaluate the importance of various prognostic features after lymphadenectomy. Univariate analysis identified the prognostic significance of clinical stage for lesions with a depth of 0.76 to 4.0 mm (p = 0.0018); number of involved nodes (p = 0.0001); Breslow's thickness (p = 0.0487); gender (p = 0.0103); location on an extremity (p = 0.0104); synchronous versus asynchronous detection of nodal metastases (p = 0.0107); age as a continuous variable (p = 0.0670); and unknown primary site (p = 0.088). Multifactorial analysis showed that number of involved nodes (p = 0.0001), extremity location of primary (p = 0.0059), and Breslow thickness (p = 0.0334) maintained their significance, whereas gender (p = 0.0627) and clinical stage (p = 0.0942) were almost significant. The long-term survival of the entire patient population at 5, 10, and 15 years of follow-up was estimated to be 46%, 41%, and 38%. When individual characteristics found to be significant by multivariate analysis were combined into different subsets, there was considerable heterogeneity, with 5-year survival varying from 79% to 14%. To quantify this heterogeneity better, a mathematical model was developed and found to approximate closely the observed survival rates in the heterogenous subsets and in the group as a whole.

Analysis of Variance↗
PubMed1989

Prognostic significance of pregnancy in stage I melanoma.

The clinical course of 66 patients with stage I melanoma, diagnosed during pregnancy, treated in the Division of Surgical Oncology at UCLA, was retrospectively reviewed. These patients were compared with 619 nonpregnant female patients with melanoma. There was no significant difference between the pregnant population and control population with respect to location of the primary tumor, age at diagnosis, Clark's level, mean depth of invasion (pregnant females, 1.24 mm vs control, 1.28 mm), and histologic type. The 5-year survival for the women diagnosed with melanoma during pregnancy and for the entire population was 86% and 87%, respectively. These results demonstrate that women diagnosed with melanoma during pregnancy fare no worse than their nonpregnant counterparts. Criteria other than the theoretical effect of pregnancy on the tumor should be used to counsel patients diagnosed with melanoma during pregnancy.

Adolescent↗
PubMed1989

Active specific immunotherapy in malignant melanoma.

We have recently initiated clinical trials of active specific immunotherapy evaluating a new polyvalent melanoma cell vaccine in patients with high-risk and/or recurrent melanoma. The vaccine has been administered alone, or in combination with low-dose cyclophosphamide, as an immunomodulator of suppressor cells. Cyclophosphamide is effective in lowering suppressor cell activity in some patients undergoing active specific immunotherapy. This is not associated with an enhanced humoral immune response to melanoma-associated antigens, nor is the clinical course of those patients receiving cyclophosphamide favorably influenced. We are hopeful that other immunomodulators, alone or in combination with lower doses of cyclophosphamide, may be effective in some patients, particularly in those patients whose suppressor cell activity remains high. The optimization of the vaccine and the use of immunomodulators will enhance humoral and cellular immune responses to antigens in the allogenic vaccine that cross react with those present in the autologous melanoma, which should more favorably influence the prognosis of melanoma patients.

Antigens, Neoplasm↗
PubMed1986

Recurrence potential of thin primary melanomas.

Between April 1971 and January 1985, the University of California at Los Angeles (UCLA) Division of Surgical Oncology has seen 649 patients diagnosed with thin primary melanomas, as defined by a Clark level less than IV and Breslow depth less than 0.76 mm. Thirty-six patients, whose primary diagnosis was confirmed by UCLA pathologists, presented with or subsequently developed melanoma metastases. Twenty-four (67%) had Clark level II lesions, whereas the remaining 12 (33%) had Clark level III lesions. Metastases were noted more frequently in men than in women, with a man-to-woman ratio of 3 to 2. The site of the primary lesion in this group was most frequently on the trunk (16 of 36 cases, 44%), followed by the head and neck (9 of 36 cases, 25%) and arm and shoulder (7 of 36 cases, 19%). Metastasizing thin lesions were least likely to occur on the leg and hip (4 of 36 cases, 11%). Twenty of these lesions were recently reexamined, and 17 of 20 cases (85%) demonstrated evidence of regression. Twenty-eight patients (78%) had their first metastases to regional lymph nodes. Fifteen remained alive with no evidence of disease at a median follow-up of 99 months. Twenty patients died from systemic metastases, and one patient was alive with brain metastasis at the time of this article. Although infrequent, metastases from thin melanomas do occur, suggesting the need for careful long-term follow-up and immediate investigation of adenopathy even in low-risk patients.

Adult↗
PubMed1975

Sequential evaluation of general immune competence in cancer patients: correlation with clinical course.

An evaluation of general immunologic reactivity was performed in 116 patients with malignant melanoma and in 40 patients with skeletal and soft tissue sarcoma who received adjunctive immunotherapy. An excellent correlation was observed between delayed cutaneous hypersensitivity to DNCB and the clinical extent of malignancy. Eighty percent of patients with Stage I disease were DNCB positive, whereas only 37% of Stage III patients were reactive on initial testing. A method for sequential evaluation of DNCB response was established, and revealed that variations in immune reactivity occurred that also correlated with the patient's clinical course. Persistence of nonreactivity to DNCB or conversion from a reactive to an anergic status was associated with postoperative recurrence in more than 80% of the patients. Conversely, conversion from an anergic to a reactive status was observed if tumor control was achieved. These results indicate that the defect in systemic immunity is closely associated with tumor cell burden, and that sequential evaluation of DNCB reactivity is a clinically useful monitor of disease progression.

Adolescent↗
PubMedDate not supplied

Diagnostic usefulness of testing for anti-HBc IgM in acute hepatitis B.

Numerous tests to detect anti-HBc IgM have been developed and shown to have different degrees of sensitivity and specificity. One of these assays, Corzyme-M (Abbott Laboratories, North Chicago, Ill.), recently became commercially available. The present study was undertaken to evaluate the clinical utility of this anti-HBc IgM test in establishing the diagnosis of acute hepatitis B using sera from a group of 42 prospectively followed individuals who had been exposed to hepatitis B virus. The Corzyme-M test was highly sensitive in detecting recent hepatitis B virus infection. All 30 patients with symptomatic and 12 with asymptomatic acute hepatitis B virus infection developed anti-HBc IgM. However, the timing of sample testing relative to onset of symptoms in symptomatic patients was important, inasmuch as 2 of 23 patients were negative for anti-HBc IgM early in the symptomatic period, although all were HBsAg positive. The duration of anti-HBc IgM positivity after acute infection was variable, ranging from 2 to 134 weeks. In 14% of patients, anti-HBc IgM remained detectable for more than 1 year. From the data, recommendations are given regarding the usefulness of anti-HBc IgM testing in the diagnosis of acute hepatitis B virus infection.

Actuarial Analysis↗