PubMed Health⌕ Search

Biomedical subjects

L A VanderMolen

Publications and source records attributed to L A VanderMolen.

13 recordsLinked to original sources
PubMed2001

Treatment of kidney cancer with autologous tumor cell vaccines of short-term cell lines derived from renal cell carcinoma.

BACKGROUND: We established short-term cultures of autologous tumors from patients with renal carcinoma for use as active specific immunotherapy (i.e., autologous vaccine). METHODS: Between 9/91 and 9/99 the cell biology laboratory of the Hoag Cancer Center received 69 kidney tumor samples that had been surgically excised, including 43 primary tumors and 26 metastatic lesions. Efforts were made to establish short-term tumor cell cultures to use as autologous tumor cell vaccines. Prior to treatment, patients underwent a baseline skin test for delayed tumor hypersensitivity (DTH) and then received s.c. injections of 10 million irradiated tumor cells that were given with various adjuvants weekly x3 and then monthly x5. RESULTS: Cell lines were established for 55/69 patients (80%) including 36/43 (84%) from primary tumors and 19/26 (73%) from distant metastases. Vaccines were prepared for 41 patients; 27 were treated. At the time of this analysis, follow up data was available for 26 patients with a median follow up > 5 years. Treatment was well-tolerated. Of 10 patients who had no evident disease at the time of treatment, nine were alive 1-8 years later; 5/8 had conversion of their DTH test from negative to positive. For 16 patients with measurable metastatic disease at the time of treatment, there were no objective tumor responses; their median survival was 5.0 months. Among these 16 patients, only 1/8 DTH tests converted, but three had a positive baseline DTH test; one was previously treated with interleukin-2 and tumor infiltrating lymphocytes and two others were previously treated with autolymphocyte therapy. CONCLUSIONS: Vaccine therapy with short-term cultures of autologous tumor cells is feasible, well-tolerated and associated with conversion of DTH and long-term survival in patients who are free of disease at the time treatment is initiated. However, significant anti-tumor responses were not seen in patients with measurable disease at the time vaccine treatment was initiated.

Adult↗
PubMed1997

Hybrid high-dose bolus/continuous infusion interleukin-2 in patients with metastatic melanoma: a phase II trial of the Cancer Biotherapy Research Group (formerly the National Biotherapy Study Group).

PURPOSE: Interleukin-2 (IL-2) is an active agent for the treatment of melanoma. In animal studies, polyethylene glycol conjugated (PEG) IL-2 was found to be effective in certain IL-2-resistant models. Bolus/infusional IL-2 administered to approximate the pharmacokinetics of PEG-IL-2 also overcame resistance in these models. Based on these observations, the Cancer Biotherapy Research Group (CBRG) [formerly the National Biotherapy Study Group (NBSG)] previously had conducted a pilot study and then a phase I trial of bolus IL-2 followed by continuous IL-2 (NBSG 90-01). METHODS: In the current study, NBSG 92-09, a phase II trial was conducted using IL-2 at a dose of 36 MIU/m2 followed by a 72-hour continuous infusion of IL-2 at 18 MIU/m2/day, so that over 3 days a total of 90 MIU/m2 of IL-2 were delivered; the same amount as previously given during 5 days of continuous i.v. IL-2 at 18 MIU/m2/day. This schedule was repeated every 2 weeks for 2 months, and then monthly for up to 6 months. RESULTS: Twenty-two patients with metastatic melanoma were enrolled in this trial. Toxicities were qualitatively similar to those seen with other IL-2 regimens, but grade 3 and 4 toxicities were observed only in patients who received at least four cycles of treatment; only one patient went off study because of toxicity. For 18 patients with measurable disease, there were two complete and two partial responses in patients ages 32, 66, 72 and 83 years, for a response rate of 22% (6% to 48%; 95% confidence interval [Ci]). The median survival for all 21 evaluable patients enrolled in the trial was 8.5 months. CONCLUSION: The hybrid schedule of drug delivery in NBSG 92-09 allowed the same dose and intensity of IL-2 to be delivered over 3 days instead of 5 days, which resulted in fewer days of hospitalization and therefore decreased cost; but with no increase in toxicity and no decrease in efficacy in patients with metastatic melanoma.

Adult↗
PubMed1996

Phase I study of subcutaneously administered interleukin-2 in combination with interferon alfa-2a in patients with advanced cancer.

PURPOSE: Although high-dose interleukin-2 (IL-2) can produce durable remissions in a subset of responding patients with renal cell carcinoma (RCC), this occurs in the setting of significant toxicity. The purpose of this study is to define the maximum-tolerated dosage (MTD) of IL-2 and interferon alfa-2a (IFN alpha-2a) that can be administered chronically on an outpatient basis. PATIENTS AND METHODS: Fifty-three patients with advanced cancer of variable histology with good prognostic features were treated in six cohorts. Patients in cohorts one through five received IL-2 (1.5 or 3.0 x 10(6) million units (mU)/m2) Monday through Friday and IFN alpha-2a (1.5 or 3 x 10(6) mU/m2) daily for a 4-week cycle. In cohort six, IFN alpha-2a was given three times a week. Immunologic monitoring, including serum levels of soluble IL-2 receptor (sIL-2R) and neopterin, flow cytometry, and natural killer cell (NK) activity, were measured. Patients were evaluated for toxicity, response, and survival. RESULTS: Almost all patients developed grade I/II toxicities commonly associated with cytokine therapy. Symptoms were most severe with the first treatment of each week. Dose-limiting toxicities included grade III fatigue, hypotension, and creatinine elevations. The MTD was 1.5 mU/m2 daily x 5 given subcutaneously repeated weekly for IL-2 and 1.5 mU/m2 daily subcutaneously (dose level 3) for IFN. Six of 25 assessable patients with RCC (24%) achieved a partial response (PR), including four of eight patients who were previously untreated. There were no objective responses in patients with other tumors, including 12 melanoma patients. CONCLUSION: IL-2 and IFN alpha-2a can be given with tolerable toxicities on an outpatient basis and shows significant activity in patients with metastatic RCC.

Adult↗
PubMed1995

The integration of high-dose chemotherapy and biotherapy: initial 5-year experience with autologous bone marrow transplantation in a comprehensive community cancer center.

Perhaps the best example of the integration of chemotherapy and biotherapy is autologous stem cell rescue following high dose chemotherapy. This analysis was undertaken to determine the outcome for patients treated in an autologous bone marrow transplant program, which was initiated in January 1989, and to illustrate the impact which biological response modifiers have had on the toxicity, survival, and costs associated with this aggressive treatment approach. Patients with metastatic cancer and good performance status were treated according to disease-specific treatment protocols. Peripheral blood stem cells [PBSC] came into use in 1990, hematopoietic colony stimulating factors [CSFs] in 1991. Outcome was monitored prospectively from the inception of the program. Five years after the program's inception, 75 patients had undergone 96 intensive chemotherapy treatments followed by autologous PBSC rescue. This included 35 patients with breast cancer, 15 with lymphoma or Hodgkin's Disease, five ovary, four melanoma, three sarcoma, three lung cancer, three leukemia, three testicular, two myeloma, one non-lung small cell carcinoma, and one medulloblastoma. Twenty-one patients underwent back-to-back cycles of intensive therapy and rescue; 14 of whom had breast cancer. Twelve patients were treated in 1989, 14 in 1990, 18 in 1991, 14 in 1992, and 17 in 1993. While four of the first 12 patients died within 60 days of reinfusion of cells in 1989, no patients have died within this time frame as a direct result of therapy during the subsequent four years. No patients have been lost to follow-up. Median survival was only eight months in 1989, but has not been reached for subsequent years. For all patients, median failure-free survival (FFS) is 17.2 months; 1-year FFS is 57%, 2-year 36%, and 3-year 29%. Median overall survival (OS) is 30.4 months; 1-year OS 66%, 2-year 52%, and 3-year 42%. From 1990-1993, for patients with metastatic breast cancer (21), and recurrent lymphoma (15), FFS and OS are comparable to the best results published from academic teaching hospitals. Twenty-one patients have survived over two years, 18 of whom continue in remission. Patients were hospitalized for an average of 31 days in 1989, 28.9 in 1990, 24.5 in 1991, and only 13.0-14.0 days in 1992-1993. Two patients were treated entirely as outpatients. Average hospital charges for the 96 treatments have been $120,000 with a range of $15,000 to $461,000, and currently average around $100,000.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Pilot study of interleukin-2 and lymphokine-activated killer cells combined with immunomodulatory doses of chemotherapy and sequenced with interferon alfa-2a in patients with metastatic melanoma and renal cell carcinoma.

BACKGROUND: Experiments in animal tumor models suggest that the antitumor effects of interleukin-2 (IL-2) or IL-2 in combination with lymphokine-activated killer (LAK) cells can be enhanced by chemotherapy agents such as cyclophosphamide or doxorubicin or by the biologic agent interferon alpha. PURPOSE: We determined the toxicity and clinical response rate of an IL-2-LAK cell regimen modified by the addition of moderate, immunomodulatory doses of chemotherapy and sequenced with interferon alfa-2a (IFN alpha-2a) in patients with metastatic melanoma and renal cell carcinoma. METHODS: IL-2 (3-6 million units/m2 per day) was administered by continuous infusion on days 0-5 and days 11-16. LAK cells were infused on days 11 and 12 or on days 11, 12, and 14. Low doses of cyclophosphamide (300 mg/m2) and doxorubicin (25 mg/m2) were given on day 9 before the LAK cell infusions. Following the IL-2-LAK cell infusion, IFN alpha-2a (12 million units/m2) was administered for a total of nine doses to complete a cycle of treatment. A total of 89 patients were enrolled in the study. RESULTS: For each histology, there were eight partial responses in 40 assessable patients, for an overall response rate of 20% (90% confidence interval = 10%-33%). The median response duration was 5 months, although two patients with renal cell carcinoma and one patient with metastatic melanoma had almost complete disappearance of tumor and are still responding after 26+, 22+, and 26+ months, respectively. Toxic effects were severe in patients receiving the highest dose of IL-2 administered in this study and similar to those reported with other high-dose IL-2-LAK cell regimens. Although toxic effects were completely reversible in most patients, there were four treatment-related deaths. CONCLUSIONS: This regimen is active in patients with metastatic melanoma and renal cell carcinoma and produces meaningful responses in a small percentage of these patients; however, it is not clear whether cyclophosphamide, doxorubicin, and IFN alpha-2a as used in this protocol appreciably augmented the antitumor activity of the IL-2-LAK cell regimen.

Adult↗
PubMed1990

Recombinant human granulocyte-macrophage colony-stimulating factor in patients with advanced malignancy: a phase Ib trial.

We evaluated the toxic, hematopoietic, and immunomodulatory effects of recombinant human granulocyte-macrophage colony-stimulating factor (rHuGM-CSF). The rHuGM-CSF was administered at doses up to 50 micrograms/kg by daily 2-hour intravenous infusions to 11 patients with advanced malignancy. It induced dose-related increases in cells of the myeloid series, but it had no significant effect on reticulocyte or platelet counts. Bone marrow cellularity increased with higher doses of rHuGM-CSF, but there was a dose-related decrease in the number of colony-forming units--granulocyte-monocyte--and colony-forming units--granulocyte-erythrocyte-monocyte-megakaryocyte--per 10(5) bone marrow cells. The rHuGM-CSF caused transient increased expression of CD11b and CD16 on granulocytes but increased expression of HLA-DR and decreased expression of the high-affinity Fc receptor on monocytes and no change in monocyte production of H2O2. Thus, rHuGM-CSF has potent effects on granulocyte, eosinophil, and monocyte numbers in the peripheral blood and bone marrow. In addition, it enhances the expression of monocyte and granulocyte activation-associated surface markers.

Antigens, Differentiation↗
PubMed1990

Surface light chain phenotype in indolent lymphomas: lack of prognostic significance.

The indolent follicular and diffuse lymphomas are neoplasms of B-cell origin. In several other B-cell neoplastic disorders, including multiple myeloma, hairy cell leukemia, and chronic lymphocytic leukemia, the light chain isotype of the surface immunoglobulin has been reported to have prognostic significance. Patients with tumors expressing lambda light chains usually fare more poorly than those with kappa light chain-bearing tumours. We analyzed the clinical data and immunologic phenotype of 101 patients with indolent lymphoma. Eighty-nine of the 101 patients demonstrated surface immunoglobulin of only one light chain type (kappa-47, lambda-42). Patients in both groups were matched for known prognostic factors. There were no significant differences in disease-free survival or overall survival between the two groups or within histologic subtypes. These results indicate that the immunologic light chain phenotype in indolent lymphoma, unlike other B-cell neoplasms, is not a prognostic indicator of survival.

Humans↗
PubMed1990

Intraperitoneal lymphokine-activated killer-cell and interleukin-2 therapy for malignancies limited to the peritoneal cavity.

Autologous lymphokine-activated killer (LAK) cells and recombinant human interleukin-2 (rIL-2) were administered intraperitoneally (IP) to 24 patients with malignancies limited to the peritoneal space. Ten patients had ovarian cancer, 12 had colorectal cancer, and one patient each had endometrial carcinoma and primary small-bowel adenocarcinoma. All ovarian cancer patients, three of twelve colorectal cancer patients, and one patient with endometrial carcinoma had received prior therapy. Patients received IL-2 100,000 U/kg every 8 hours intravenously (IV) for 3 days, and 2 days later underwent daily leukapheresis for 5 days. LAK cells were generated in vitro by incubating the peripheral blood mononuclear cells in IL-2 for 7 days and were then administered IP daily for 5 days through a Tenckhoff catheter (Davol, Inc, Cranston, RI) together with IL-2 25,000 U/kg IP every 8 hours. All but one patient completed at least one cycle of therapy. Toxic side effects included minor to moderate hypotension, fever, chills, rash, nausea, vomiting, abdominal pain and distension, diarrhea, oliguria, fluid retention, thrombocytopenia, and minor elevations of liver function tests; all of these rapidly improved after discontinuation of IL-2. One patient had a grand mal seizure, and one suffered a colonic perforation; these were felt to be treatment-related. IP fibrosis developed in 14 patients and limited repeated cyclic administration of this therapy in five patients. Two of 10 (20%) ovarian cancer patients and five of 12 (42%) colorectal cancer patients had laparoscopy- or laparotomy-documented partial responses. We conclude that LAK cells and rIL-2 can be administered IP to cancer patients, resulting in moderate to severe short-term toxicity and modest therapeutic efficacy. Further investigation of this form of adoptive immunotherapy modified to address the problem of IP fibrosis and with lower IP IL-2 doses is justified by these initial results.

Adult↗
PubMed1989

Diffuse osteosclerosis in hairy cell leukemia.

We describe two patients with a new clinical pathologic syndrome of diffuse osteosclerosis in association with hairy cell leukemia. In both patients bone marrow biopsies could not be obtained due to extremely hard bones and inability to insert the biopsy needle; neither patient had a history of bony pain or fracture. The osteosclerotic process in one patient stabilized after successful treatment of her hairy cell leukemia with interferon alpha and deoxycoformycin suggesting that the osteosclerosis observed was related to the underlying malignant disease. Possible etiologic mechanisms are discussed.

Adult↗