PubMed Health⌕ Search

Biomedical subjects

S Osanto

Publications and source records attributed to S Osanto.

At least 37 records · Page 2Linked to original sources
PubMed1999

Pharmacokinetics of interleukin-2 in two anephric patients with metastatic renal cell cancer.

BACKGROUND: Most patients with metastatic renal cell carcinoma (RCC) have undergone unilateral- and some bilateral nephrectomy. Because interleukin-2 (IL-2) is thought to be mainly cleared via the kidneys, we investigated whether IL-2 treatment is safe in anephric patients. PATIENTS AND METHODS: The pharmacokinetics of i.v. bolus, i.v. infusion and s.c. recombinant IL-2 were investigated in two anephric patients with progressive metastatic RCC. RESULTS: Following i.v. bolus administration of IL-2, plasma half-lives of 126 and 84 minutes respectively, and plasma clearances of 151 ml/min and 273 ml/min respectively, were measured in the two patients. In one patient plasma clearance of IL-2 was enhanced to 760 ml/min after continuous i.v. infusion of 4 and 6 million IU IL-2/24 hours, as compared to a clearance of 310 ml/min at a dose of 2 million IU IL-2/24 hours. In the other patient, during IL-2 infusion of 2, 4 or 6 x 10(6) IU/24 hours, each over the course of 3 days, plasma clearance of IL-2 increased from 311 to 761, and to 687 ml/min, respectively. IL-2 could not be detected in haemo- or peritoneal dialysates. CONCLUSIONS: IL-2 plasma half-life is only moderately prolonged in anephric patients as compared to patients with normal renal function. Based on our findings, intravenous or subcutaneous treatment of anephric patients with IL-2 seems feasible.

Aged↗
PubMed1998

Cisplatin combination chemotherapy induces a fall in plasma antioxidants of cancer patients.

BACKGROUND: Antioxidants protect the body against cellular oxidative damage and thus some of the adverse effects induced by cisplatin and other cytostatic drugs. PATIENTS AND METHODS: The effect of cisplatin-combination chemotherapy on concentrations of plasma antioxidants was studied in 36 cancer patients, including osteosarcoma and testicular carcinoma patients. RESULTS: Eight to 15 days after the start of each cytostatic drug infusion concentrations of various plasma antioxidants were measured and compared to pretreatment values: vitamin C and E, uric acid and ceruloplasmin levels fell significantly (P < 0.01-0.005) and returned to baseline levels before the start of the next chemotherapy cycle. Levels of the antioxidants bilirubin albumin and the ratio vitamin E/cholesterol + triglycerides measured three weeks after the start of chemotherapy significantly decreased compared to pretreatment levels and remained low thereafter (P < 0.001-0.002). Dietary intake of antioxidants and anthropometric measurements, evaluated in 14 patients did not change during the whole treatment period. CONCLUSIONS: Cisplatin-combination chemotherapy induces a fall in plasma antioxidant levels, that may reflect a failure of the antioxidant defense mechanism against oxidative damage induced by commonly used anticancer drugs. This probably results from consumption of antioxidants caused by chemotherapy induced-oxidative stress as well as renal loss of water-soluble, small molecular weight antioxidants such as uric acid.

Adolescent↗
PubMed1998

Definition of unique and shared T-cell defined tumor antigens in human renal cell carcinoma.

From peripheral blood mononuclear cells of a patient with renal cell carcinoma (RCC), we isolated several T-cell clones, which efficiently lyse the autologous RCC cell line (LE-8915-RCC), but not the autologous Epstein Barr virus-transformed lymphoblastoid cell line. Most of the cytotoxic T lymphocyte (CTL) clones recognize HLA-A1-positive allogeneic RCC cell lines, indicating that HLA-A1 is the restricting element for these T cells. One CTL clone exclusively recognizes the autologous tumor cells. The HLA-A1-restricted CTL clones can be divided further into two subsets of T-cell clones, one blocked by an HLA-A1-specific monoclonal antibody, the other not. The reactivity of HLA-A1-restricted T-cell clone 6/135 was studied in greater detail. This T-cell clone also recognizes a number of melanoma cell lines, indicating that expression of the antigen seen by this CTL clone is not restricted to RCC. Strikingly, the antigen is not exclusively expressed by tumor cell lines, because primary cultures of proximal tubulus epithelium cells, adult mesangial cells, and normal breast epithelium cells are also lysed. These results corroborate the notion that renal carcinoma cells are immunogenic by virtue of a broadly distributed antigenic structure that may serve as a target for cytotoxic T cells and may be a potential candidate for tumor vaccine development.

Antibody Specificity↗
PubMed1997

Transfection of IL-2 augments CTL response to human melanoma cells in vitro: immunological characterization of a melanoma vaccine.

We have transfected human melanoma cell line 518A2 with the cDNA encoding interleukin-2 (IL-2) or granulocyte-macrophage colony-stimulating factor (GM-CSF), and compared cytokine-producing clones for their ability to induce melanoma-specific cytotoxic T lymphocytes (CTL) from autologous peripheral blood mononuclear cells (PBMC) in vitro. The parental cell line expressed HLA-A1, HLA-A2, ICAM-1, LFA-3, in addition to the common CTL antigens MAGE-1, MAGE-3, tyrosinase, gp100, and Melan-A/MART-1. Stimulation of autologous PBMC responders with the IL-2-transfected clone 518/IL2.14 specifically induced CTL lines reactive with all cell lines derived from the autologous patient. Strikingly, GM-CSF-transfected 518A2 cells did not induce anti-tumor CTL reactivity. CTL induction against 518/IL2.14 was independent of HLA class II expression or CD4 help. The parental cell line 518A2 gained immunogenic properties when high concentrations of IL-2 were supplied exogenously, indicating that IL-2 produced and present at high levels locally by itself enhanced immunogenicity. From the autologous CTL line reactive with 518/IL2.14, clones were generated against an as yet unknown antigen, which was present in all autologous melanoma cell lines as well as in 7 of 15 HLA-A2+ melanoma cell lines tested, but not in melanocytes. These results will be discussed with respect to the possibility of using IL-2-transfected melanoma cells as a vaccine for treatment of patients with melanoma.

Cancer Vaccines↗
PubMed1997

Vaccine Trials for the Clinician: Prospects for Tumor Antigens.

Recent insights in antigen presentation, the identification of human tumor antigens, and the demonstration of MHC class-I-restricted cytotoxic T lymphocyte (CTL) recognition of peptides encoded by tumor antigen have renewed the interest and enthusiasm for the development of cancer vaccines. Melanoma serves as a paradigm of an immunogenic human tumor, and several tumor antigens, including MAGE, MART-1/Melan-A and gp100, recognized by CTLs, have now been isolated. Candidate antigens for novel vaccine trials may include HLA class-I-binding tumor peptides that serve as CTL epitopes, whole tumor protein, or DNA-based vaccines. Requirements for the use of peptides are that the patient's tumor presents the relevant CTL epitopes as used in the vaccine and expresses the appropriate MHC class-I-restricting molecule. Immunological monitoring may be facilitated when using peptide-based vaccines. Because optimal presentation of tumor antigens may depend on provision of appropriate costimulatory signals, it may be more advantageous to administer professional antigen-presenting cells (APCs), such as dendritic cells (DCs) pulsed with tumor peptide or protein, to cancer patients. Developments in molecular genetics have led to a new approach in vaccines consisting of cancer cells genetically engineered to express immunomodulatory molecules. This may result in increased antitumor responses to both gene-modified as well as unmodified tumor cells. The therapeutic approach is extended to vaccination trials with recombinant viruses containing the genes encoding tumor antigens, minigenes containing multiple CTL epitopes, or double recombinant vectors engineered to express both the tumor antigen and immunostimulatory molecules. Clinical peptide, protein and DNA-based vaccine trials have recently been initiated. Thus far, exciting clinical remissions were obtained in melanoma patients following vaccination with HLA-A1-binding MAGE-3 peptide and in B-cell lymphoma patients immunized with autologous DCs pulsed with anti-idiotype protein, i.e., the individual patient's unique tumor antigen. Also, following injection of foreign HLA-B7 DNA into cutaneous melanoma metastases, T-cell migration into treated lesions and enhanced cellular immunity at the site of the tumor were shown in some patients. These encouraging results suggest that effective new vaccines in cancer will be identified.

Journal Article↗
PubMed1996

Renal-cell carcinoma-specific lysis by cytotoxic T-lymphocyte clones isolated from peripheral blood lymphocytes and tumor-infiltrating lymphocytes.

Melanoma and renal-cell carcinoma (RCC) are generally considered to be relatively immunogenic tumor types in humans. In the case of melanoma, many major histocompatibility complex (MHC) class I-restricted tumor-specific cytotoxic T lymphocytes (CTL) have been isolated from either tumor-infiltrating lymphocytes (TIL) or autologous peripheral blood lymphocytes (PBL). In contrast, such CTL have only incidentally been described in the case of RCC. It has often been reported that TIL lines isolated from RCC display non-MHC-restricted and non-specific activity. Here, we report the isolation and characterization of tumor-specific CTL from PBL of one RCC patient and from TIL of another RCC patient. CTL clones 263/17 and 263/45, isolated from the PBL of patient LE-9211, were restricted by HLA-B7. CTL clone 5E, isolated from the TIL of patient LE-8915, was restricted by HLA-B37. The autologous RCC cell lines were efficiently lysed by the CTL clones, whereas normal epithelial cells of the proximal tubuli matched for the restriction element and K562 were not. From a panel of allogeneic RCC cell lines, CTL 5E recognized MZ-1940-RCC. Reactivity to allogeneic RCC sharing HLA-B7 was also observed with CTL 263/17 and 263/45, both of which could lyse the HLA-B7-positive cell line MZ-1851-RCC. Our data provide evidence that common tumor antigens are recognized by CTL on RCC.

Carcinoma, Renal Cell↗
PubMed1994

Frequencies of HPRT mutants and micronuclei in lymphocytes of cancer patients under chemotherapy: a prospective study.

Fifteen cancer patients, including 10 testicular carcinoma patients, were treated with several types of combination chemotherapy. Blood samples were collected before, during and after chemotherapy. Subsequently, lymphocytes were analyzed for frequencies of HPRT mutants (MF) and micronuclei (MNF). Significantly elevated MFs were detected in eight patients. Mean expression time (+/- SD) for mutations was 98 +/- 54 days (range: 42-172 days). In some patients, enhanced MFs persisted for a period of 430-490 days after cessation of chemotherapy. In five patients MNFs were increased 2-6-fold and the enhancement was fairly persistent. Ifosfamide and cyclophosphamide appeared to be the most mutagenic and clastogenic constituents of the chemotherapy, while evidence for adverse effects of adriamycin, 4-epi-adriamycin and bleomycin was equivocal. Results indicate that the clinical use of mutagenic drugs must be weighed against the risks of persistent genetic damage and secondary malignancies in cured patients and their potential offspring. Further studies are necessary to determine the true risks and incidence of such abnormalities following chemotherapy for curable forms of cancer.

Adolescent↗
PubMed1994

Transduction of human melanoma cells with interleukin-2 gene reduces tumorigenicity and enhances host antitumor immunity: a nude mouse model.

Human melanoma tumor cells were genetically modified in vitro by transferring the interleukin-2 (IL-2) gene via a retroviral vector into established or fresh tumor cells. In addition, human melanoma cells were transduced in vivo by the direct injection of the IL-2/retroviral vector into melanoma xenografts in nude mice. The gene-modified melanoma cells expressed the IL-2 cytokine gene and secreted biologically active IL-2. Transduction of melanoma cells with the IL-2 gene did not affect the antigenic profile of the cells, but caused a strong abrogation of their tumorigenicity. One million parental cells formed subcutaneous tumors in nude mice. In contrast, various doses of up to 20 x 10(6) IL-2-transduced cells failed to form tumor in the mice. Coinjection of IL-2-producing cells with parental cells inhibited tumor formation even when highly tumorigenic doses of parental cells were used. Histochemical analysis of the injection sites of IL-2-modified cells showed an influx of host immune cells, predominantly macrophages, as early as the third day after inoculation. Neutrophils, mast cells, and eosinophils were also seen in the inflammatory exudate. Eventually, transduced cells showed signs of degeneration and necrosis and ultimately died in 4 weeks. Macrophages were seen in parental tumor sites only during the first few days after injection, and then parental tumors exhibited fast, progressive growth. The study suggests that melanoma cells transduced with the IL-2 cytokine gene may provide an effective vaccine for melanoma patients, whereas the in vivo transduction of tumors with cytokine genes is feasible and may represent a novel approach for the immunotherapy of cancer patients.

Animals↗
PubMed1994

Transduction of human melanoma cells with the gamma interferon gene enhances cellular immunity.

Human tumor cells transduced with the gamma interferon (gamma IFN) gene are currently used in specific active immunotherapy protocols to enhance the antitumor immune responses of cancer patients. This in vitro study was undertaken to examine the initial events in the cellular immune response that may occur following the administration of the gamma IFN-transduced cell vaccine. Human melanoma tumor cell lines were transduced with a MoMLV-based retroviral vector carrying the human gamma IFN gene. The transduced cells expressed the cytokine gene, secreted biologically active gamma IFN, and exhibited enhanced expression of MHC class I and class II (HLA-DR), and ICAM-1 surface antigens. The gamma IFN-transduced and corresponding parental melanoma cells were used for the induction of short-term lymphocyte cultures. Peripheral blood lymphocytes or lymph node cells from 20 melanoma patients were stimulated for 5 to 15 days with autologous or MHC class I-matched allogeneic parental or gamma IFN-transduced melanoma cells. Seven of the 20 lymphocyte cultures showed substantial increases in lytic activity following stimulation with the transduced melanoma cells in comparison to control lymphocyte cultures stimulated with unmodified parental melanoma. The cytolytic activity stimulated with gamma IFN-modified melanomas was mediated partly by MHC-restricted cytotoxic T lymphocytes and partly by NK cells. Lymphocyte cultures that displayed increases in cytotoxicity after stimulation with the gamma IFN-transduced melanoma cells also exhibited enhanced expression or induction of one or more of the following lymphokines: IL-4, IL-1 alpha, IL-1 beta, gamma IFN, and TNF-alpha.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens, Neoplasm↗
PubMed1993

Immunization with interleukin-2 transfected melanoma cells. A phase I-II study in patients with metastatic melanoma.

The safety, tolerance and clinical effects of immunization with irradiated, allogeneic melanoma cells that express high levels of HLA-A1 and -A2 and secrete IL-2 after transfection with the Interleukin-2 gene, will be assessed in HLA-A1 or HLA-A2 positive melanoma patients with metastatic disease. As a pilot, the first 5-10 patients, if no immediate regression of tumor lesions are observed, will in addition to immunization with these allogeneic tumor cells receive recombinant IL-2 in relatively low doses during three consecutive weeks on an outpatient basis. If no clinical remissions are induced in these first 5-10 patients, subsequent 5-10 patients will receive the same dose of melanoma cells without additional rIL-2. Thereafter the dose of injected melanoma cells will be increased in every following 5-10 patients, but all subsequent patients will receive only IL-2 producing, allogeneic tumor cells, without the addition of rIL-2.

Clinical Protocols↗
PubMed1993

Hypothyroidism during immunotherapy with interleukin-2 is associated with antithyroid antibodies and response to treatment.

PURPOSE: We investigated whether the association of interleukin-2 (IL-2) with hypothyroidism is related to the presence of thyroid autoantibodies, dose of IL-2, and clinical effectiveness of treatment, and reviewed the literature. PATIENTS AND METHODS: Sixteen cancer patients were treated with high-dose recombinant, continuous infusion IL-2 (18 x 10(6) IU/m2/d) and lymphokine-activated killer (LAK) cells. One patient previously treated for a toxic goiter with radioactive iodine was analyzed separately. Thyroid function and levels of thyroid antibodies were determined regularly. RESULTS: Seven of 15 patients (47%) became hypothyroid with high serum thyrotropin (TSH) levels within 60 to 120 days after the start of treatment; five responded favorably to treatment (one complete remission [CR], four partial remissions [PRs]), compared with none of the other eight patients. Two hypothyroid patients developed antimicrosomal antibodies (AMAs), one showed a further increase of antithyroglobulin antibodies (TgAbs), and six developed TgAbs. Only one of eight euthyroid patients developed slightly elevated TgAb levels. Development of hypothyroidism correlated significantly with a favorable response to treatment (r = .76, P = .001). The patient, treated with radioactive iodine, also became hypothyroid with high levels of TSH and development of AMAs and TgAbs. No difference was found between the hypothyroid and euthyroid patients in mean cumulative dose of IL-2 administered within the first 60 days or total treatment period, or with the relative dose-intensity. No other autoantibodies were found and patients had normal corticotropin (ACTH) stimulation tests. CONCLUSION: The likelihood of developing (transient) hypothyroidism is higher in patients who respond to IL-2 treatment. The development of antithyroid antibodies suggests that IL-2 treatment triggers autoreactive B-cell clones or that cellular and/or cytokine-mediated thyroid destruction leads to activation of autoreactive B-cell clones.

Adult↗
PubMed1992

Downmodulation of c-myc expression by interferon gamma and tumour necrosis factor alpha precedes growth arrest in human melanoma cells.

After in vitro incubation of melanoma tumour cells Cmel453A with either recombinant interferon gamma (rIFN-gamma) or tumour necrosis factor alpha (rTNF-alpha) a dose-dependent inhibition of cell growth occurred; when both cytokines were added, a synergistic action was observed. Inhibition of DNA synthesis, as measured by [3H] thymidine incorporation, occurred after 6 h of incubation with rIFN-gamma or rTNF-alpha, and this action was potentiated when the two cytokines were applied simultaneously. Within 1 h, the level of c-myc mRNA in tumour cells had already decreased by, respectively, 60% (S.D. 7) and 25% (S.D. 7); the combined addition of the cytokines resulted in a greater reduction of c-myc mRNA than by each cytokine alone. Downregulation of c-myc expression is an early event, occurring hours before the actual inhibition of outgrowth. Thus, in melanoma cells like Cmel with a high constitutive expression of the c-myc oncogene, the antiproliferative action of rIFN-gamma and rTNF-alpha may be mediated by an inhibition of the expression of c-myc.

Antigens, Neoplasm↗
PubMed1992

Long-term effects of chemotherapy in patients with testicular cancer.

PURPOSE: Combination chemotherapy regimens that include cisplatin (CDDP) and bleomycin (BLE) result in the cure of the majority of patients with malignant germ cell tumors of the testis. We investigated the long-term damage of such chemotherapy to renal, pulmonary, and hearing function. PATIENTS AND METHODS: Forty-three patients with disseminated testicular carcinoma were studied 1.5 to 9.3 years (median, 4.1 years) after completion of chemotherapy. All 43 patients received CDDP; of these, 39 also received BLE, 27 vinblastine (VLB), and 27 etoposide (VP-16). Mean cumulative doses of individual cytotoxic drugs administered were CDDP 483 mg/m2 (range, 189 to 1,173 mg/m2), BLE 160 mg/m2 (range, 81 to 311 mg/m2), VLB 31 mg/m2 (range, 19 to 158 mg/m2), and VP-16 667 mg/m2 (range, 242 to 1,455 mg/m2). RESULTS: In the majority of cases, values of renal, pulmonary, and hearing function were within the normal range before treatment. An initial decrease in renal, pulmonary, and hearing function was observed, with recovery of pulmonary function at late follow-up. On average, a decrease of 15% in creatinine clearance rates was observed at late follow-up. Long-term effect on audiometric function was considerable, but frequencies affected were outside the range of conversational speech. With multivariate analysis, no overall relation between the cumulative doses of the individual drugs and the loss in organ function was found; the cumulative doses of CDDP and BLE only contributed approximately 30% to the loss in renal function and vital capacity, respectively. CONCLUSION: Chemotherapy-induced pulmonary toxicity is reversible, whereas nephrotoxicity and ototoxicity are not. However, the long-term effects of chemotherapy in testicular cancer patients were minor and not invalidating.

Adult↗
PubMed1991

In vivo production of interleukin-5, granulocyte-macrophage colony-stimulating factor, macrophages colony-stimulating factor, and interleukin-6 during intravenous administration of high-dose interleukin-2 in cancer patients.

Recombinant human interleukin-2 (IL-2), administered to cancer patients by continuous intravenous (IV) infusion (3 x 10(6) U/m2/d), was found to induce the in vivo production of colony-stimulating factors (CSF). Plasma obtained from patients during IL-2 treatment stimulated in vitro colony formation of normal human bone marrow cells, depleted of mononuclear phagocytes and T lymphocytes. This colony-stimulating activity (CSA) was identified as IL-5, granulocyte-macrophage CSF (GM-CSF), and macrophage CSF (M-CSF), by the ability of specific antibodies against these factors to neutralize their effects. The presence of IL-2-induced GM-CSF and M-CSF was also demonstrated by specific radioimmunoassays. During IL-2 treatment, plasma also contained detectable levels of IL-6, which was measured in a bioassay. Using a cDNA-polymerase chain reaction (PCR) with specific primer sets for the various CSF, we showed that IL-2 treatment induced the expression of mRNA for M-CSF, GM-CSF, IL-3, and IL-5, but not for granulocyte CSF (G-CSF) in peripheral blood mononuclear cells, suggesting differential expression of CSF in vivo in response to IL-2. Furthermore, no negative regulators of hematopoiesis, such as interferon gamma (IFN-gamma) or tumor necrosis factor-alpha (TNF-alpha), were found in plasma. These data illustrate that in vivo administration of high-dose IL-2 may result in a stimulatory effect on hematopoiesis. The induction of detectable levels of IL-5 and GM-CSF in the circulation may explain the eosinophilia and neutrophilia observed in these patients.

Carcinoma, Renal Cell↗
PubMed1991

Increased frequency of chromosomal damage in peripheral blood lymphocytes up to nine years following curative chemotherapy of patients with testicular carcinoma.

The presence of micronuclei (MN) in binucleated peripheral blood lymphocytes of 37 testicular carcinoma patients was studied 1.5 to 9.3 years following curative chemotherapy. All patients received cisplatinum, 35 patients also received bleomycin. In addition, most patients were treated with another cytotoxic drug, i.e., vinblastine (n = 23) and/or etoposide (n = 24). The mean time interval between cessation of chemotherapy and the micronucleus assay was 4.6 years. The median frequency of MN in binucleated cells in treated patients (0.059) was significantly higher than that in 12 untreated cancer patients (0.036; P = 0.003) or that in 26 healthy age-matched controls (0.034; P less than 0.001). Frequencies of MN in the 12 untreated cancer patients (including 7 patients with disseminated testicular carcinoma) did not differ from those in the 26 healthy controls (P = 0.890), suggesting that chromosomal damage in lymphocytes of treated testicular cancer patients must be attributed to the chemotherapy. Results indicate that lymphocytes containing chemically induced chromosomal damage persist for up to 9.3 years following cessation of chemotherapy. The implications of these findings with regard to the increased risk for secondary tumors are discussed.

Adult↗
PubMed1991

Increased intracellular killing of bacteria in vitro by monocytes of patients with metastatic melanoma before and during treatment with interferon-gamma and interferon-alpha.

The effect of recombinant human interferon-gamma (rHuIFN-gamma) and interferon-alpha (rHuIFN-alpha) as in vivo stimuli for the activation of human monocytes was investigated on the basis of the bactericidal activity of peripheral blood monocytes in 11 patients with metastatic melanoma before and during treatment with interferons. Patients received increasing doses of rHuIFN-gamma and a fixed dose of rHuIFN-alpha, both administered subcutaneously three times a week. The rates of intracellular killing of Listeria monocytogenes and Salmonella typhimurium after in vitro phagocytosis by monocytes collected from melanoma patients before interferon treatment were increased (P less than 0.01) by a factor of 1.7 and 1.4, respectively, relative to the rate constants in blood monocytes of healthy donors. During treatment with the interferons, the rates of intracellular killing of the bacteria by patients' monocytes did not further increase. The findings underscore the immunogenicity of malignant melanoma and put into question the macrophage activating activity of IFN-gamma with respect to the bactericidal activity of monocytes.

Adult↗
PubMed1990

Increased numbers of circulating haematopoietic progenitor cells after treatment with high-dose interleukin-2 in cancer patients.

Immunotherapy with recombinant interleukin-2 (IL-2) and lymphokine-activated killer (LAK) cells has been applied to patients with metastatic cancers for its antitumour activity. In the present study we investigated the effects of in vivo administration of IL-2 (3 x 10(6) U/m2/d, continuously i.v.) on haematopoiesis. Six patients with disseminated renal cell carcinoma, treated with IL-2 and LAK cells, were monitored for the numbers of white blood cells and circulating haematopoietic progenitor cells (HPC). During IL-2 treatment lymphopenia developed, followed by lymphocytosis after discontinuation of IL-2 infusions. IL-2 administration also resulted in neutrophilia and eosinophilia. Absolute numbers of circulating HPC declined markedly during IL-2 treatment. However, after completing IL-2 infusions, the numbers of circulating erythroid (BFU-E), myeloid (CFU-GM) and multipotential progenitor cells (CFU-GEMM) strongly increased, reaching a maximum after 5 d (day 10 from the start of IL-2 treatment). This increase did not result from repeated leucaphereses, since patients treated with IL-2 alone showed a similar response. In comparison with pretreatment levels the pool of circulating HPC expanded about 20-fold. This study illustrates that IL-2 treatment has a biphasic effect on the frequency of circulating BFU-E, CFU-GM and CFU-GEMM, causing a decrease during IL-2 infusion, followed by an increase after IL-2 administration. The total number of progenitor cells harvested by four consecutive leucaphereses is in the range that is commonly used for peripheral blood stem cell autografting.

Carcinoma, Renal Cell↗