Primary Thromboprophylaxis in Patients with Malignancies: Daily Practice Recommendations by the Hemostasis Working Party of the German Society of Hematology and Medical Oncology (DGHO), the Society of Thrombosis and Hemostasis Research (GTH), and the Austrian Society of Hematology and Oncology (ÖGHO).

Patients with cancer, both hematologic and solid malignancies, are at increased risk for thrombosis and thromboembolism. In addition to general risk factors such as immobility and major surgery, shared by non-cancer patients, cancer patients are exposed to specific thrombotic risk factors. These include, among other factors, cancer-induced hypercoagulation, and chemotherapy-mediated endothelial dysfunction as well as tumor-cell-derived microparticles.

Bortezomib and low-dose dexamethasone with or without continuous low-dose oral cyclophosphamide for primary refractory or relapsed multiple myeloma: a randomized phase III study.

This phase III, open-label, randomized, controlled study aimed to evaluate the benefit of adding continuous low-dose oral cyclophosphamide to bortezomib-dexamethasone in patients with primary relapsed/refractory multiple myeloma. Patients were randomized 1:1 to receive up to eight 3-week cycles of bortezomib (1.3 mg/m) and dexamethasone (20 mg; VD; n = 48) or bortezomib-dexamethasone plus oral cyclophosphamide (50 mg; VCD; n = 48).

Diagnosis, prevention, and management of bleeding episodes in Philadelphia-negative myeloproliferative neoplasms: recommendations by the Hemostasis Working Party of the German Society of Hematology and Medical Oncology (DGHO) and the Society of Thrombosis and Hemostasis Research (GTH).

Philadelphia-negative myeloproliferative neoplasms (Ph-negative MPN) comprise a heterogeneous group of chronic hematologic malignancies. The quality of life, morbidity, and mortality of patients with MPN are primarily affected by disease-related symptoms, thromboembolic and hemorrhagic complications, and progression to myelofibrosis and acute leukemia. Major bleeding represents a common and important complication in MPN, and the incidence of such bleeding events will become even more relevant in the future due to the increasing disease prevalence and survival of MPN patients.

Cancer Screening in Patients with Idiopathic Venous Thromboembolism--a Position Paper of the German Society of Hematology and Oncology Working Group on Hemostasis.

Cancer can trigger thromboembolism. There is a 4-10% chance of finding an asymptomatic occult cancer in patients with idiopathic venous thromboembolism (VTE). Current guidelines recommend limited cancer screening with history, physical examination, and screening examinations according to age after idiopathic VTE.

Laparoscopic splenectomy for medically refractory immune thrombocytopenia (ITP): a retrospective cohort study on longtime response predicting factors based on consensus criteria.

Background: Laparoscopic splenectomy has been proposed to be the standard therapy for adult patients with medically refractory immune thrombocytopenia (ITP). However, due to inconsistent definitions of response, variable rates of long term response have been reported. Furthermore, new medical treatment options are currently challenging the role of splenectomy.

Minireview: Malassezia infections in immunocompromised patients.

Malassezia spp. form part of the normal human cutaneous flora and are implicated in several mild, but recurrent cutaneous diseases, such as pityriasis versicolor, Malassezia folliculitis, seborrhoeic dermatitis, and, with lesser frequency, a range of other dermatological disorders. Malassezia spp.

An open-label dose-escalation study of BIBF 1120 in patients with relapsed or refractory multiple myeloma.

Background: To determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of BIBF 1120, a triple angiokinase inhibitor administered once-daily in patients with advanced multiple myeloma.

Patients And Methods: This Phase I study included 17 patients. Planned dose escalations of BIBF 1120 were 100, 200, 250 and 300 mg.

Activated human gammadelta T cells as stimulators of specific CD8+ T-cell responses to subdominant Epstein Barr virus epitopes: potential for immunotherapy of cancer.

The efficacy of current cancer vaccines is limited by the functional heterogeneity and poor availability and expansion of professional antigen-presenting cells (APCs). Besides their potent innate effector properties, gammadelta T cells have been suggested to be involved in the initiation and maintenance of adaptive immune responses. Here, we investigated the capacity of human gammadelta T cells to induce expansion of virus-specific T cells to Epstein Barr virus (EBV) antigens.

Bortezomib, dexamethasone, and fibroblast growth factor receptor 3-specific tyrosine kinase inhibitor in t(4;14) myeloma.

Purpose: Novel drugs including targeted approaches have changed treatment paradigms for multiple myeloma (MM) and may also have therapeutic potential in the poor-prognosis t(4;14) subset; t(4;14) results in overexpressed and activated fibroblast growth factor receptor 3 (FGFR3). Blocking this receptor tyrosine kinase (RTK) induces apoptosis in t(4;14)+ MM cells and decreases adhesion to bone marrow stromal cells (BMSC). Using combinations of novel drugs, we investigated potential enhancement of single-agent activities within the tumor cells, targeting of the marrow micromilieu, or circumvention of drug resistance in t(4;14)+ MM.

Paracrine interactions of vascular endothelial growth factor and platelet-derived growth factor in endothelial and lung cancer cells.

While the effects of single growth factors on endothelial cells (ECs) have been extensively studied, the importance of induction of growth factors such as PDGF-BB (platelet derived growth factor) in ECs and its impact on tumor cell functions are only partly understood. Human umbilical vein endothelial cells (HUVECs) were cultured under serum-free conditions and stimulated by 20 ng/ml VEGF (vascular endothelial growth factor) or 20 ng/ml bFGF (basic fibroblastic growth factor). As determined by real-time PCR, both VEGF and bFGF induced a significant (up to 4-fold) increase in PDGF-B RNA expression which was time- and dose-dependent (p<0.

Bortezomib in combination with intermediate-dose dexamethasone and continuous low-dose oral cyclophosphamide for relapsed multiple myeloma.

A phase 2 trial was performed to study the combination of bortezomib (VELCADE) with intermediate-dose dexamethasone (DEX), and continuous low-dose oral cyclophosphamide (CY) in patients with relapsed multiple myeloma (MM). Fifty-four patients with advanced MM were enroled to receive eight 3-week treatment cycles with bortezomib 1.3 mg/m(2) on days 1, 4, 8, and 11, followed by three 5-week cycles with bortezomib 1.

Differential requirement for a cellular type-1 immune response in tumor-associated versus alloantigen-targeted GvT effects.

Background: The major obstacles that impair successful outcome after allogeneic hematopoietic stem cell transplantation (HSCT) for hematologic malignancies remain graft-versus-host disease (GvHD) and tumor relapse. Improved survival after allogeneic HSCT therefore requires more effective control of GvHD while preserving graft-versus-tumor (GvT) effects.

Methods: Allogeneic parent-into-F1 murine transplant models (BALB/c or C57BL/6 --> F1[BALB/cxC57BL/6]) were used to evaluate the interrelation of GvHD and GvT effects targeting tumor-specific antigens or alloantigens on MethA tumor cells.

Growth inhibition and induction of apoptosis in acute myeloid leukemia cells by new indolinone derivatives targeting fibroblast growth factor, platelet-derived growth factor, and vascular endothelial growth factor receptors.

In acute myeloid leukemia (AML), receptor tyrosine kinase ligands promote growth and survival and contribute to AML-associated marrow neoangiogenesis. We have tested simultaneous inhibition of vascular endothelial growth factor, fibroblast growth factor, and platelet-derived growth factor receptor signaling by novel indolinone derivatives using 14 myeloid, including 11 human leukemic, cell lines. Compounds inhibited colony formation of all cell lines in a dose-dependent fashion.

Proteasome inhibition in multiple myeloma.

The ubiquitin-proteasome pathway is the major cellular degradative system for various proteins critical for proliferation, survival and homing of myeloma cells. Bortezomib is the first specific and reversible proteasome inhibitor for clinical application in humans. Phase I studies have defined the maximum tolerated dose and suggested activity against multiple myeloma.

Targeting receptor kinases by a novel indolinone derivative in multiple myeloma: abrogation of stroma-derived interleukin-6 secretion and induction of apoptosis in cytogenetically defined subgroups.

In multiple myeloma (MM), both vascular endothelial (VEGF) and basic fibroblast growth factor (bFGF) promote tumor growth and survival. We have used the novel indolinone BIBF 1000 to study effects of simultaneous inhibition of VEGF, FGF and transforming growth factor-beta on MM cells and their interactions with bone marrow stroma cells (BMSCs). Both, in the absence and presence of myeloma-stroma cell contacts, BIBF 1000 abrogated BMSC-derived secretion of interleukin-6 (IL-6).

Bortezomib in combination with dexamethasone for relapsed multiple myeloma.

Fifteen patients with advanced multiple myeloma were scheduled to receive bortezomib 1.3 mg/m2 IV days 1, 4, 8, and 11 every 3 weeks for eight cycles in combination with dexamethasone. One patient (7%) achieved a complete response, 10 (67%) a partial response, and one (7%) a minor response (MR) resulting in an overall response rate (> or = MR) of 80% (9/9 with > or = 2nd untreated and 3/6 with refractory relapse).

Graft-versus-host disease after allogeneic hematopoietic stem cell transplantation induces a CD8+ T cell-mediated graft-versus-tumor effect that is independent of the recognition of alloantigenic tumor targets.

Cure of hematologic malignancies after allogeneic hematopoietic stem cell transplantation is partially attributable to immunocellular antitumor reactions termed graft-versus-tumor (GvT) effect. GvT effects are heterogeneous with respect to effector cell populations, target antigens, and their interrelation with graft-versus-host disease (GvHD). In the present study, allogeneic parent-into-F1 murine transplantation models (BALB/c or C57BL/6 --> [C57BL/6 x BALB/c]F1) with different tumors derived from either parental strain were used to evaluate tumor-specific GvT effects.

Hyperfractionated cyclophosphamide in combination with pulsed dexamethasone and thalidomide (HyperCDT) in primary refractory or relapsed multiple myeloma.

Sixty patients with advanced multiple myeloma received 2-6 monthly treatment courses combining hyperfractionated cyclophosphamide (300 mg/m2 i.v. over 3 h q 12 h x 6, d 1-3) with pulsed dexamethasone (20 mg/m2/d p.

Paracrine interactions of basic fibroblast growth factor and interleukin-6 in multiple myeloma.

Myeloma cells express basic fibroblast growth factor (bFGF), an angiogenic cytokine triggering marrow neovascularization in multiple myeloma (MM). In solid tumors and some lymphohematopoietic malignancies, angiogenic cytokines have also been shown to stimulate tumor growth via paracrine pathways. Since interleukin-6 (IL-6) is a potent growth and survival factor for myeloma cells, we have studied the effects of bFGF on IL-6 secretion by bone marrow stromal cells (BMSCs) and its potential reverse regulation in myeloma cells.

Common bile duct obstruction due to candidiasis.

Biliary obstruction with its wide range of potential causes (e.g. neoplastic lesions, gallstones and inflammatory processes) is a common disease in gastroenterology.