Activin A inhibits BMP-signaling by binding ACVR2A and ACVR2B.

Background: Activins are members of the TGF-β family of ligands that have multiple biological functions in embryonic stem cells as well as in differentiated tissue. Serum levels of activin A were found to be elevated in pathological conditions such as cachexia, osteoporosis and cancer. Signaling by activin A through canonical ALK4-ACVR2 receptor complexes activates the transcription factors SMAD2 and SMAD3.

Effects of peripheral blood stem cell apheresis on systemic cytokine levels in patients with multiple myeloma.

BACKGROUND AIMS. Pro-angiogenic cytokines can affect myeloma cell proliferation directly and indirectly through stimulation of cancer-associated angiogenesis. METHODS.

Effect of pamidronate 30 mg versus 90 mg on physical function in patients with newly diagnosed multiple myeloma (Nordic Myeloma Study Group): a double-blind, randomised controlled trial.

Background: Compared with placebo, prophylactic treatment with bisphosphonates reduces risk of skeletal events in patients with multiple myeloma. However, because of toxicity associated with long-term bisphosphonate treatment, establishing the lowest effective dose is important. This study compared the effect of two doses of pamidronate on health-related quality of life and skeletal morbidity in patients with newly diagnosed multiple myeloma.

Melphalan and prednisone plus thalidomide or placebo in elderly patients with multiple myeloma.

In this double-blind, placebo-controlled study, 363 patients with untreated multiple myeloma were randomized to receive either melphalan-prednisone and thalidomide (MPT) or melphalan-prednisone and placebo (MP). The dose of melphalan was 0.25 mg/kg and prednisone was 100 mg given daily for 4 days every 6 weeks until plateau phase.

Long-term cryopreservation of autologous stem cell grafts: a clinical and experimental study of hematopoietic and immunocompetent cells.

Background: Autologous stem cell transplantation(ASCT) is used in the treatment of several malignancies.Harvesting sufficient peripheral blood progenitor cells (PBPCs) for a potential second autotransplantation at the time of relapse several years after diagnosis is becoming an increasingly common practice.

Study Design And Methods: Cryopreserved PBPCs were prepared with different concentrations of dimethyl sulfoxide (DMSO; 2, 4, 5, and 10%) and stored for at least 5 years before the recovery of CD34+ cells and various T- and natural killer (NK)-cell subsets were analyzed by flow cytometry.

Autologous peripheral blood progenitor cells cryopreserved with 5 and 10 percent dimethyl sulfoxide alone give comparable hematopoietic reconstitution after transplantation.

Background: Previous in vitro studies have demonstrated decreased apoptosis and necrosis in peripheral blood progenitor cells (PBPCs) cryopreserved with 5 percent instead of 10 percent dimethyl sulfoxide (DMSO). This study was carried out to investigate whether these in vitro findings were supported by clinical data concerning hematopoietic engraftment after autologous stem cell transplantations with PBPCs cryopreserved with 5 and 10 percent DMSO.

Study Design And Methods: During a 6-year period, 103 consecutive patients with newly diagnosed multiple myeloma (MM; n = 58) and lymphoma (n = 45) were transplanted with autologous PBPCs.

Intensive therapy for multiple myeloma in patients younger than 60 years. Long-term results focusing on the effect of the degree of response on survival and relapse pattern after transplantation.

Background And Objectives: From 1994 to 1997 we conducted a population-based, prospective study on intensive therapy in newly diagnosed symptomatic myeloma patients younger than 60 years, comparing their survival to that of a conventionally treated historic population. Long-term results are presented, including the impact of the degree of response on survival and relapse pattern after transplantation.

Design And Methods: The prospective population was formed of 397 patients and the historic population of 313 patients.

Serum levels of thrombopoietin and stem cell factor in acute leukemia patients with chemotherapy-induced cytopenia and complicating infections.

Thrombopoietin (Tpo) and stem cell factor (SCF) are growth factors for megakaryocyte progenitor cells and can also modulate platelet function. We have characterized variations in serum levels of these two cytokines in acute leukemia patients undergoing intensive chemotherapy. Compared with healthy controls, serum Tpo levels were significantly increased prior to consolidation chemotherapy, and serum levels were correlated to peripheral blood platelet counts.

Impact of age on survival after intensive therapy for multiple myeloma: a population-based study by the Nordic Myeloma Study Group.

The value of intensive therapy, including autologous stem cell transplantation, in newly diagnosed myeloma patients >60 years is not clear. We evaluated the impact of age (<60 years vs. 60-64 years) on survival in a prospective, population-based setting and compared survival with conventionally treated historic controls.

A multi-centre prospective study of febrile neutropenia in Norway: microbiological findings and antimicrobial susceptibility.

The urgent need to treat presumptive bacterial or fungal infections in neutropenic patients has meant that initial therapy is empiric and based on the pathogens most likely to be responsible, and drug resistance. The traditional empirical treatment in Norway has been penicillin G and an aminoglycoside, and this combination has been criticized over recent y. We wished to analyse the microbiological spectrum and susceptibility patterns of pathogens causing bacteraemia in febrile neutropenic patients.

[Blood transfusion and pretransfusion testing in patients with warm autoimmune haemolytic anaemia].

Background: In warm autoimmune haemolytic anaemia, patients have red cell autoantibodies that complicate the serological compatibility testing before transfusion. Different autoadsorption techniques are utilised for more extensive pretransfusion testing. We reviewed the literature on blood transfusion in these patients.

[Survival after high-dose therapy with autologous stem cell support].

Background: High-dose therapy with autologous stem cell support has been carried out in our hospital since 1996. We have recently collected survival data on patients who have undergone this procedure.

Material And Methods: The study population comprised 111 patients, 58 of whom had been diagnosed with multiple myeloma, 38 with various forms of malignant lymphoma, 11 with sarcoma and 4 with testicular cancer.

Functional characterization of T lymphocytes derived from patients with acute myelogenous leukemia and chemotherapy-induced leukopenia.

T-cell-targeting immunotherapy is now considered in acute myelogenous leukemia (AML). Immunotherapy seems most effective for patients with a low AML cell burden, and a possible strategy is therefore to administer immunotherapy early after intensive chemotherapy when patients have a low leukemia cell burden and severe treatment-induced cytopenia. To further investigate this possible therapeutic approach we used a whole blood assay to characterize the proliferative responsiveness (3H-thymidine incorporation) of circulating T cells from AML patients with severe treatment-induced leukopenia, i.

Cellular immune responses in multiple myeloma patients with treatment-induced cytopenia early after high-dose chemotherapy and autologous peripheral blood stem cell transplantation.

Proliferative T cell responses were compared for two patient groups with severe treatment-induced leukopenia (white blood cell counts < 0.5 x 10(9)/l): (i). multiple myeloma patients receiving high-dose melphalan and autologous peripheral blood stem cell transplantation; (ii).

A phase I/II study of the MDR modulator Valspodar (PSC 833) combined with daunorubicin and cytarabine in patients with relapsed and primary refractory acute myeloid leukemia.

The cyclosporine analog Valspodar (PSC 833, Novartis Pharma) is a strong inhibitor of the mdr1 gene product p-glycoprotein (pgp). A phase I/II study was conducted in order to evaluate if addition of Valspodar to treatment with daunorubicin and cytarabine, given to patients with primary refractory or relapsed acute myeloid leukemia, could increase the complete remission rate.Fifty-three patients were treated in cohorts of three to six patients.

Health-related quality of life in multiple myeloma patients receiving high-dose chemotherapy with autologous blood stem-cell support.

In a population-based study, the Nordic Myeloma Study Group found a survival advantage for high-dose melphalan with autologous blood stem-cell support compared to conventional chemotherapy in myeloma patients under 60 yr of age (risk ratio: 1.62; confidence interval [CI] 1.22-2.

[High dose therapy with autologous stem cell support--finally a progress in myelomatosis].

Background: Since the introduction of the simple cyclic oral treatment with melphalan and prednisone in the late 1960s, there has been no substantial improvement in the therapy of multiple myeloma. In 1994, the Nordic Myeloma Study Group initiated a population-based, prospective study to evaluate the impact on survival of high dose chemotherapy in newly diagnosed, symptomatic patients under 60 years of age, compared to a conventionally treated control group.

Material And Methods: 274 patients were treated according to a specified high dose protocol and compared to 274 patients from previous population-based trials fulfilling the same eligibility criteria.

Malignancy: Insulin-like Growth Factor-1 (IGF-1) is a Costimulator of the Expansion of Lineage Committed Cells Derived from Peripheral Blood Mobilized CD34+ Cells in Multiple Myeloma Patients.

The effect of insulin-like growth factor-1 (IGF-1) on highly enriched human apheresis CD34(+) progenitor cells was investigated in vitro. The progenitor cells were mobilized by treatment with cyclophosphamide + granulocyte - colony stimulating factor (G-CSF) in patients with multiple myeloma. CD34(+) cells were cultured for 7 days in serumfree medium containing stem cell factor (SCF), granulocyte-macrophage colony stimulating factor (GM-CSF) and interleukin-3 (IL-3), and this is referred to as cytokine-dependent proliferation.

[High dose chemotherapy with autologous stem cell support in cancer patients].

Introduction: In 1996 it was decided that high-dose chemotherapy with peripheral stem cell support should be offered by all five university hospitals in Norway.

Material And Methods: We report on the first 49 patients from the western part of Norway treated with this modality at Haukeland University Hospital in the 1996-98 period.

Results: All patients had a total of > 2-10(6) CD34 positive cells/kg collected before high-dose chemotherapy.

Impact on survival of high-dose therapy with autologous stem cell support in patients younger than 60 years with newly diagnosed multiple myeloma: a population-based study. Nordic Myeloma Study Group.

High-dose therapy has become a common treatment for myeloma. The objectives of this study were to estimate in a prospective, population-based setting the impact on survival of high-dose therapy in newly diagnosed, symptomatic patients less than 60 years old and to compare the results with those of conventionally treated historic controls. The prospective population comprised 348 patients.

[Chronic myeloid leukemia in health regions 1, 3, 4 and 5 during the period 1990-96].

The aim of the present investigation was to obtain information about treatment, clinical course and outcome for all patients with chronic myeloid leukaemia through a six-year period in a defined part of Norway. A total number of 141 patients fulfilled the diagnostic criteria. This is equivalent to 0.

Insulin-like Growth Factor-1 (IGF-1) is a Costimulator of the Expansion of Lineage Committed Cells Derived from Peripheral Blood Mobilized CD34(+) Cells in Multiple Myeloma Patients.

The effect of insulin-like growth factor-1 (IGF-1) on highly enriched human apheresis CD34(+) progenitor cells was investigated in vitro. The progenitor cells were mobilized by treatment with cyclophosphamide + granulocyte-colony stimulating factor (G-CSF) in patients with multiple myeloma. CD34(+) cells were cultured for 7 days in serumfree medium containing stem cell factor (SCF), granulocyte-macrophage colony stimulating factor (GM-CSF) and interleukin-3 (IL-3), and this is referred to as cytokine-dependent proliferation.

[The POEMS syndrome--a rare multiorgan disease].

POEMS syndrome is a rare multisystemic disorder characterized by a variable constellation of polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes. The syndrome is believed to be immune-mediated and is probably related to the pathological monoclonal component caused by a myeloma or a plasmocytoma. The treatment is aimed at the underlying plasma cell dyscrasia.

T-lymphocyte functions in acute leukaemia patients with severe chemotherapy-induced cytopenia: characterization of clonogenic T-cell proliferation.

Intensive chemotherapy for acute leukaemia is followed by a period of severe chemotherapy-induced leukopenia. We used a limiting dilution assay to investigate whether remaining CD4+ and CD8+ T lymphocytes derived from such leukopenic patients could be activated and undergo clonogenic proliferation. The activation signal in our model was accessory cells (irradiated normal peripheral blood mononuclear cells) + phytohaemagglutinin (PHA) + interleukin-2 (IL-2).

Interleukin 4 responses in acute leukaemia patients with severe chemotherapy-induced leucopenia.

T lymphocyte functions in acute leukaemia patients with severe chemotherapy-induced leucopenia were investigated using 3 different approaches: (i) analysis of serum concentrations of the T cell cytokine interleukin 4 (IL4) demonstrated that serum IL4 levels increased during complicating bacterial infections. However, this response was modulated by a concomitant increase in serum levels of the potential IL4 antagonist soluble IL4 receptor alpha chain (sIL4R alpha). (ii) Even during leucopenia a subset of T lymphocytes derived from leucopenic patients expressed the activation markers CD25 (IL2 receptor), CD71 (transferrin receptor) and HLA-DR.