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T T Pelliniemi

Publications and source records attributed to T T Pelliniemi.

At least 19 recordsLinked to original sources
PubMed2001

Feasibility of prolonged use of interferon-alpha in metastatic kidney carcinoma: a phase II study.

BACKGROUND: Interferon-alpha has proven effective in the treatment of metastatic renal cell carcinoma. However, the optimal schedule has not yet been determined. The authors have studied the efficacy and toxicity of prolonged use interferon-alpha2a (IFN-alpha) in metastatic renal cell carcinoma (RCC). Interferon-alpha was administered intermittently for outpatients. METHODS: Seventy-five patients with metastatic RCC without prior biochemotherapy were treated. During the first month, the IFN-alpha dose was increased from 4.5 to 18 million units (MU) 3 times a week to define the individual maximal tolerated dose for each patient. The treatment was continued at the maximal tolerated dose with a 1-week pause each month until either progression or intolerable toxicity was observed or up to 2 years. RESULTS: The overall response rate (5 complete response [CRs] and 8 partial responses [PRs]) was 17% (95% confidence interval, 10-28%). Stable disease was observed in 32 patients (43%). Three late objective responses (4%) occurred after 12 months treatment. The median progression free time of all patients was 12.3 months, and median survival time was 19.3 months. The median duration of response in CR/PR patients was 16 months. In multivariate analysis independent prognostic factors were poor performance status (P = 0.004), presence of bone metastases (P = 0.001), and time to metastases less than 24 months (P = 0.003), which predicted poor survival. Six patients (8%) discontinued the treatment because of fatigue, elevation of liver enzymes, or cardiac arrhythmias. No life-threatening side effects were observed. CONCLUSIONS: Prolonged and intermittently administered IFN-alpha2a three times per week in 3 weekly cycles in metastatic RCC is a feasible and effective therapy. A prolonged treatment duration of more than 12 months for stable and responding patients is beneficial and may improve the outcome of patients with RCC.

Adult↗
PubMed2000

Serum oncostatin M in multiple myeloma: impact on disease severity and prognosis.

Since high levels of serum IL-6 predict a poor prognosis of patients with multiple myeloma (MM), we investigated if a related cytokine, oncostatin M (OSM), correlates with clinical or biochemical findings or has prognostic significance in patients with MM. Among 82 newly diagnosed MM patients, OSM was detected in the sera in 45 (55%). Serum OSM had a borderline statistical correlation with serum IL-6 (r = 0.198, p = 0.074) and C-reactive protein (r = 0.199, p = 0.074) concentrations. However, OSM did not have prognostic significance alone or in combination with other factors. The median survival of patients with detectable serum OSM concentration was 41 months (range 2-124 months) and of OSM negative patients 35 months (1-75 months). Serum OSM concentration was not associated with clinical factors or severity of bone disease at diagnosis. We conclude that serum OSM concentration is not a prognostic factor in MM patients.

Adult↗
PubMed1998

Plasma cell leukemia 3 months after autologous blood cell transplantation for multiple myeloma.

We describe a patient with multiple myeloma who was treated with intensive therapy and autologous blood cell transplantation as her first-line treatment. The disease relapsed 3 months after the transplant as plasma cell leukemia and the patient succumbed in 4 weeks. We suggest that an aggressive plasma cell clone may be selected during the course of intensive treatment. Complex karyotypic findings are also presented.

Adult↗
PubMed1998

Comparison between four and eight cycles of intensive chemotherapy in adult acute myeloid leukemia: a randomized trial of the Finnish Leukemia Group.

In acute myelogenous leukemia (AML) intensive postremission treatment is needed for an optimal result. However, it is not known how long the treatment should last and how many courses are necessary. The object of this prospective study was to compare four and eight intensive chemotherapy cycles in the treatment of adult de novo AML. In a multicenter study, 248 consecutive patients, aged from 16 to 65 years, were treated with intensive induction treatment. The patients in remission after two courses were randomized to receive either two (short arm) or six (long arm) additional intensive cycles of chemotherapy. The median follow-up time of the living patients is 68 months. Of the patients, 77% achieved complete remission, and 36% of all patients survived for 5 years. Seventy-three patients were randomized to the short arm and 66 to the long arm. There was no significant difference in the relapse-free survival (median 21 months vs 17 months) or overall survival (43 months vs 39 months) between the short and long arms, respectively. Treatment-related deaths occurred in 31 patients (13%), 11 of them in first remission. More than one-third of the patients survived for 5 years. It seems probable that the first few months after diagnosis are decisive for the prognosis if the chemotherapy is intensive, and further treatment cannot markedly influence the outcome.

Aclarubicin↗
PubMed1998

Long-term treatment with GM-CSF in patients with chronic lymphocytic leukemia and recurrent neutropenic infections.

In this prospective study we evaluated the multiple effects of long-term GM-CSF therapy on blood counts, granulocyte functions and disease progression in patients with chronic lymphocytic leukemia (CLL) with chronic neutropenia and recurrent bacterial infections. The treatment duration varied from 2 to 12 weeks. The neutrophil count was raised in all patients, by the median of 6.6-fold. The neutrophil level of 1.0 x 10(9)/l was usually reached after two weeks. The initial dose of GM-CSF was 5 microg/kg/day, and 1-7 microg/kg/day was required to maintain the neutrophil level above 1.0 x 10(9)/l. Granulocyte functions, i.e. chemiluminescence (CL), random migration, and fMLP-stimulated chemotaxis were initially depressed in all patients when compared to healthy controls. GM-CSF enhanced significantly CL even when given at small doses (less than 1 microg/kg/day), even lower than the dose required to promote granulopoiesis. We conclude that GM-CSF is effective in improving CLL associated chronic neutropenia and also enhances impaired granulocyte chemiluminescence. Thus, GM-CSF could be helpful for giving chemotherapy without neutropenic delays and for prophylaxis of infectious complications in CLL patients.

Aged↗
PubMed1997

Intensive chemotherapy of poor prognosis myelodysplastic syndromes (MDS) and acute myeloid leukemia following MDS with idarubicin and cytarabine.

Forty patients with high risk myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) preceded by MDS were treated with intensive induction and consolidation chemotherapy in a prospective multicenter pilot study. They were given two cycles of cytarabine 100 mg/m with 12-h intervals on days 1-7 and idarubicin 12 mg/m2 on days 5-7, both intravenously. Patients who were in remission after these two cycles were given two further cycles of cytarabine on days 1-5 and idarubicin on day 5. No maintenance treatment was given. Eleven out of 19 MDS patients (58%) and 10 out of 21 AML patients (48%), in total 21 out of 40 patients (53%), entered remission. Eight patients underwent allogeneic bone marrow transplantation. The follow-up time was 13-48 (median 33) months. At the time of the analysis, seven patients survived, four patients with MDS all of whom had been treated with bone marrow transplantation (three in continuous remission), and three patients with AML treated with chemotherapy only (two in continuous remission). The median survival of the patients treated with chemotherapy only was 12 months, with the median progression-free survival being 8 months. In view of the poor prognostic factors of the patients, the remission rate was satisfactory, but the responses as well as the survival were short. The post-remission treatment needs to be improved.

Adult↗
PubMed1997

Autologous blood cell transplantation in B-CLL: response to chemotherapy prior to mobilization predicts the stem cell yield.

Successful stem cell mobilization and collection is possible in B-CLL after a favorable response to preceding chemotherapy, and also after treatment with the new nucleoside analogues fludarabine and cladribine. A poor response, on the other hand, seemed to predict a mobilization failure. CD34+ cell selection resulted in a 2- to 3-log reduction of the CLL cells in the harvests. Engraftment with both unselected and selected progenitor cells was rapid, and need for hospitalization was short. High-dose therapy with stem cell rescue appears to be capable of inducing CRs of high quality, but so far the follow-up is too short to define whether this will be translated into prolonged disease-free survival.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

Serum oncostatin M in multiple myeloma: association with prognostic factors.

The serum concentration of oncostatin M (OSM) was measured in 40 multiple myeloma patients at diagnosis. Serum OSM level exceeded the sensitivity limit of the ELISA assay in eight (20%) of these patients (OSM+ patients). The serum levels of IL-6, another member of the gp180 cytokine family and C-reactive protein (CRP) as a surrogate of IL-6 were significantly higher in OSM+ patients. There was a trend towards higher serum beta 2M concentration in OSM+ patients, whereas there was no difference in the serum sIL-6R level or clinical data (age, gender, myeloma protein or stage) between the two groups. Two human myeloma cell lines secreted OSM and IL-6, but not IL-11 or leukaemia inhibitory factor (LIF), which suggests an important role for OSM and IL-6 in supporting growth of myeloma cells.

Aged↗
PubMed1997

Febrile infection changes the expression of IgG Fc receptors and complement receptors in human neutrophils in vivo.

We have examined the expression of the IgG Fc receptors (FcRI, FcRII, FcRIII) and complement receptors (CR1, CR3) in neutrophils from 42 patients with febrile bacterial infection, 20 patients with febrile viral infection and 69 non-febrile healthy individuals. Using receptor-specific MoAbs and immunofluorescence flow cytometry the relative fluorescence intensity (as a measure of receptor number) and the proportion of receptor-positive cells were determined in peripheral blood neutrophils exposed to minimal processing, consisting only of erythrolysis. Both the percentage of FcRI-positive neutrophils and FcRI number per neutrophil were significantly (P < 0.001 and P < 0.0001) increased in bacterial infected patients compared with controls, whereas in viral infected patients only the FcRI percentage was markedly elevated (P < 0.05). In addition, both FcRII and CR1 levels were significantly higher in the bacterial infection group than in the viral infection and control groups (bacterial versus control P < 0.001, bacterial versus viral P < 0.0001). No changes in expression of FcRIII or CR3 were found in the patient groups. The kinetic analysis of receptor expression in bacterial infection patients revealed a shift in the percentage of FcRI-bearing neutrophils towards normal values already on day 2 after the first analysis. On the other hand, the levels of FcRI, FcRII and CR1 remained clearly elevated in these patients during 1 week's follow-up period. We conclude that febrile infection may cause systemic activation of the entire pool of circulating neutrophils, resulting in alterations in cell surface receptor expression, some of which are characteristic of the nature of the infectious agent.

Adolescent↗
PubMed1997

Daily measurements of blood CD34+ cells after stem cell mobilization predict stem cell yield and posttransplant hematopoietic recovery.

The value of daily monitoring of the blood CD34+ cell concentration as a guide to the optimal timing of stem cell harvests was studied in 60 patients who underwent 66 stem cell mobilizations and 189 leukaphereses. There was a highly significant correlation between the blood CD34+ count and the CD34+ cell content in the apheresis product of the same day (r = 0.904, p < 0.01). Thus, the target yield of 4 x 10(6) CD34+ cells/kg can be harvested in one or two leukaphereses when the blood CD34+ cell count exceeds 50 x 10(6)/L. However, an insufficient harvest is to be expected when the blood CD34+ cell count is below 20 x 10(6)/L. The data from 35 autologous blood cell transplantations with a minimum CD34+ cell yield of 1.5 x 10(6)/kg showed that the recovery of blood neutrophil counts to 1.0 x 10(9)/L occurred in all patients within 9-14 days, but the time to recovery of the platelet counts to 20 x 10(9)/L may exceed 14 days, especially if the CD34+ cell content is below 4 x 10(6)/kg. Daily monitoring of blood CD34+ cell counts is a rapid and reliable means to guide the timing of stem cell collections. The count predicts well the CD34+ cell content of the harvests, the number of leukaphereses needed, and the speed of hematopoietic recovery.

Adult↗
PubMed1997

Type I diabetic pregnancy and subclinical human papillomavirus infection.

It has been suggested that diabetic pregnancy is an immunosuppressive state. To determine whether the possible immunosuppression in pregnant diabetics might result in an increased risk for human papillomavirus (HPV) infection, we studied exfoliated cells from the uterine cervix, vagina, and posterior commissure of the vulva by means of dot blot hybridization with use of a probe cocktail of HPV types 11, 16, and 18 under low stringency and by means of consensus primer-mediated polymerase chain reaction (PCR) targeted to the HPV L1 and E1 regions. For this study, samples from 31 pregnant diabetics whose glucose levels had been reasonably well controlled were analyzed during the first trimester; samples from 27 of these patients were analyzed again during the third trimester. Fifty-one healthy pregnant women were included as controls. Only one of the pregnant diabetics was positive for HPV DNA. The L1 PCR products of the first and third trimester samples from this patient were sequenced, and both were found to represent HPV 61. Three of the pregnant controls were positive for HPV: two were positive for HPV 16, and one was positive for HPV 6. The 95% confidence limits for the prevalence of HPV were calculated to be 0.1%-16.7% for the diabetics and 1.2%-16.2% for the controls. The 95% confidence limits for the difference between the groups were -11.6%-6.3%. These results suggest that pregnant diabetics do not have an increased risk of developing HPV infection, at least when their glucose levels remain well controlled.

Adult↗
PubMed1997

High-dose chemotherapy with autologous stem cell support for the treatment of advanced ovarian cancer--initial experience in Uppsala and Turku.

BACKGROUND: With current standard-dose chemotherapy ovarian cancer is a chemosensitive but not chemocurable disease in the majority of cases. The widely used first-line chemotherapy including a platinum analogue combined with cyclophosphamide results in response rates of 60-80%. However, only 10-20% of patients with advanced disease are alive 5 years after the diagnosis. The efficacy of high-dose chemotherapy supported by autologous stem cell transplantation (ASCT) is currently under intensive investigation. METHODS: We report here our initial experiences of the use of high-dose chemotherapy supported by ASCT for patients with high-risk ovarian cancer. Two patients were treated at Uppsala University Hospital in 1992 and four patients at Turku University Central Hospital in 1994. RESULTS: The first four patients treated either after heavy previous chemotherapy or recurrent disease relapsed within 5-10 months. Two patients received high-dose therapy as part of first-line treatment. One of them had a relapse 18 months after therapy, the other one has been disease free for 28 months. No toxic deaths occurred, but the patients had neutropenic febrile episodes and moderate to severe gastrointestinal toxicity. CONCLUSIONS: Coordinated efforts in Nordic countries are indicated to evaluate the usefulness of high-dose therapy supported by ASCT in the treatment of advanced ovarian cancer.

Adult↗
PubMed1997

p53 gene mutations are rare in patients but common in patient-originating cell lines in multiple myeloma.

We have shown previously that detectable serum concentration of p53 protein is associated with poor prognosis in multiple myeloma (MM). In this study, we studied p53 gene mutations in 29 bone marrow samples of MM patients using polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) and direct sequencing. No p53 mutations were found in these patients although 41% of the patients had an elevated serum p53 protein concentration. This result indicates that the detectable serum level of p53 protein is not associated with p53 mutations. In addition, we have also analysed three MM cell lines established from bone marrow samples. All the cell lines contained p53 mutations in exon 5. However, bone marrow samples of the patients associated with the cell lines did not have these mutations at the time of diagnosis, nor did the original samples which were used to establish the cell lines. This indicates that p53 mutations can arise during the cell passages.

Adult↗
PubMed1996

GM-CSF raises serum levels of beta 2-microglobulin and thymidine kinase in patients with chronic lymphocytic leukaemia.

The effects of granulocyte-macrophage colony-stimulating factor (GM-CSF) on biochemical tumour markers beta 2-microglobulin (beta 2m), thymidine kinase (TK) and lactate dehydrogenase (LDH) were studied in eight patients with chronic lymphocytic leukaemia (CLL). The serum concentration of beta 2m rose by a median of 30% (range 8-50%) and serum TK by 101% (range 30-1414%). Serum LDH concentration, on the other hand, significantly decreased in all patients. The significant increases of beta 2m and TK could not be explained by progression of the disease or impaired renal function. Treatment with GM-CSF reduces the value of serum beta 2m and TK in assessment of tumour mass and disease activity.

Aged↗
PubMed1996

Soluble interleukin-6 receptor as a prognostic factor in multiple myeloma. Finnish Leukaemia Group.

Interleukin-6 (IL-6) is a major growth factor for the clonal malignant plasma cells in multiple myeloma (MM). The effect of IL-6 may be enhanced by soluble IL-6 receptor (sIL-6R). As there is a clinical need for improved stratification of MM patients at diagnosis, we have studied the role of sIL-6R as a prognostic marker in 207 newly diagnosed MM patients. Serum sIL-6R concentration was above the upper reference limit in 47% of the patients at diagnosis. The concentrations of sIL-6R and two other prognostic factors, IL-6 and beta-2 microglobulin (beta 2M), were all significantly higher in the patients who died within 3 years compared with those who survived. However, serum sIL-6R did not show linear correlation with IL-6 or beta 2M levels. In univariate logistic regression analysis sIL-6R was a significant predictor of 3-year mortality. Kaplan-Meier analysis showed that raised levels of sIL-6r were associated with shorter survival. When the patients were stratified into four groups according to their serum IL-6 and sIL-6R levels the patients with normal serum levels of both parameters had clear survival benefit. As beta 2M was the most powerful prognostic factor in the multivariate analysis, the patients were also stratified according to their serum beta 2M and sIL-6R levels. The patients with raised levels of both beta 2M and sIL-6R had shorter survival than the patients in the other three groups. Thus, measurement of these parameters at diagnosis would help to stratify MM patients.

Adult↗
PubMed1996

Effects of alpha-interferon on serum beta-2-microglobulin.

Beta-2-microglobulin (B2M) forms the small invariable light chain subunit of class I HLA antigens on the cell membrane of all nucleated cells. During the continuous turnover of the HLA molecules, B2M is shed from the cell membrane into blood. Lymphocytes are the main source of serum free B2M. Serum B2M concentration is increased in renal diseases, various malignant diseases and some inflammatory and autoimmune disorders. In lymphatic malignancies serum B2M has significant prognostic value. Interferons (IFNs) have the ability to enhance the expression of class I and II histocompatibility antigens. Accordingly, IFNs cause a rise in formation and release of B2M. Currently, treatment with IFN alpha is used in diseases, like multiple myeloma, where serum B2M measurements are used to assess tumor burden. We have measured serum B2M levels during IFN alpha treatment in patients with both multiple myeloma and chronic myeloproliferative diseases, and IFN alpha caused a significant increase in serum B2M. It can be concluded that use of IFN alpha abolishes the value of serum B2M as an indicator of disease activity.

Humans↗