Immune activating and inhibiting effects of calcitriol on γδ T cells and NK cells.

The immune modulatory effects of vitamin D and the impact of vitamin D deficiency on various diseases are a subject of current scientific research. However, there are few data directly linking vitamin D to hard endpoints in clinical studies, apart from its well-known effects on bone health. It is therefore of interest, that the effectiveness of the therapeutic antibody rituximab is connected to the vitamin D serum level of patients with B cell lymphomas.

Dexa-BEAM versus MIFAP as salvage regimen for recurrent lymphoma: a prospective randomized multicenter phase II trial with a median follow-up of 14.4 years.

Purpose: The aim of this study was to prospectively compare the MIFAP protocol, which had been shown to be effective in patients with relapsed and refractory Hodgkin's lymphoma (HL) or aggressive non-Hodgkin's lymphoma (NHL), to an established regimen like Dexa-BEAM.

Methods: Seventy-three adult patients with HL (N = 25) or aggressive NHL (N = 48) suffering from relapse or refractory disease were randomly allocated to receive two cycles of Dexa-BEAM (dexamethasone, carmustine, etoposide, cytarabine, melphalan; N = 37) or MIFAP (mitoxantrone, fludarabine, cytarabine, cisplatin; N = 36) prior to a consolidating high-dose therapy and hematopoietic cell transplantation (HCT). Primary endpoint was the overall response rate (ORR) [complete response (CR) and partial response (PR)] after two courses of salvage chemotherapy.

Improving Immunotherapy Against B-Cell Malignancies Using γδ T-Cell-specific Stimulation and Therapeutic Monoclonal Antibodies.

Tumor antigen-targeting monoclonal antibodies (mAbs) are an important element of current cancer therapies. Some of these therapeutic mAbs enable antibody-dependent cell mediated cytotoxicity (ADCC) against tumor cells. However, cancer-related functional impairment of immune effector cells may limit the clinical efficacy of antibody treatments.

PD-1 signaling modulates interferon-γ production by Gamma Delta (γδ) T-Cells in response to leukemia.

Gamma delta (γδ) T-cell based immunotherapy is a promising concept for the treatment of hematologic malignancies. Not only but also in early phase clinical trials, zoledronic acid (Zol) and interleukin-2 (IL-2) have been successfully used to activate human γδ T-cells and to induce clinical anti-tumor effects. Aiming to improve the effectiveness of future γδ T-cell based immunotherapies against leukemia, we analyzed the impact of programmed cell death protein 1 (PD-1) signaling, on the different phases of γδ T-cell activation, of proliferation, production of anti-tumor cytokines and cytotoxic function .

Addressing Unmet Information Needs: Results of a Clinician-Led Consultation Service About Complementary and Alternative Medicine for Cancer Patients and Their Relatives.

Purpose: To report on a telephone consultation service with cancer patients and their relatives about complementary and alternative medicine (CAM) between 1999 and 2011.

Methods: We offered a Germany-wide, free-of-charge telephone consultation service about CAM led by oncology clinicians from a comprehensive cancer center. The consultations followed a patient-centered approach with the aim to provide guidance and evidence-based information.

Azathioprine-induced reversible EBV-associated Hodgkin-like lymphoma after immunosuppressive therapy for autoimmune hepatitis .

The use of immunosuppressive agents is associated with an increased risk of the development of certain types of malignancies, particularly lymphoma. Many of these lymphomas are associated with Epstein-Barr virus (EBV), which might be reactivated under immunosuppression. We present the case of a patient with an autoimmune hepatitis who developed EBV-associated Hodgkin-like lymphoma under immunosuppressive treatment with azathioprine.

Severe Drug-Induced Liver Injury as an Adverse Drug Event of Antibiotics: A Case Report and Review of the Literature.

Drug-induced liver injury is one of the main reasons for acute liver failure. We report the case of a young patient who experienced a drug-induced liver injury resulting in life-threatening acute liver failure after treatment with different antibiotics (amoxicillin, ciprofloxacin, cefazolin, clindamycin) and acetaminophen, or a combination of these drugs. Moreover, we provide an overview of the hepatotoxic potential of these drugs.

Refractory plasmablastic lymphoma-a review of treatment options beyond standard therapy.

Plasmablastic lymphoma (PBL) is a rare distinct subtype of aggressive diffuse large B-cell lymphoma and a notoriously hard to treat entity with a dismal prognosis in both HIV-negative and HIV-positive patients. Clinicians often face the question of second or third line treatment. As the treatment options with novel agents in lymphomas are rapidly evolving, more and more options beyond standard chemotherapy are available.

Addition of high-dose cytarabine to immunochemotherapy before autologous stem-cell transplantation in patients aged 65 years or younger with mantle cell lymphoma (MCL Younger): a randomised, open-label, phase 3 trial of the European Mantle Cell Lymphoma Network.

Background: Mantle cell lymphoma is characterised by a poor long-term prognosis. The European Mantle Cell Lymphoma Network aimed to investigate whether the introduction of high-dose cytarabine to immunochemotherapy before autologous stem-cell transplantation (ASCT) improves outcome.

Methods: This randomised, open-label, parallel-group, phase 3 trial was done in 128 haemato-oncological hospital departments or private practices in Germany, France, Belgium, and Poland.

Prospective, Multicenter Study of 5-Fluorouracil Therapeutic Drug Monitoring in Metastatic Colorectal Cancer Treated in Routine Clinical Practice.

Background: Studies have demonstrated that body surface area-based dosing of chemotherapy drugs leads to significant individual exposure variability, with a substantial risk of under- or overdosing. The present study was initiated to validate the use of therapeutic drug management (TDM) to personalize 5-fluorouracil (5-FU) dosing in patients with metastatic colorectal cancer treated in routine clinical practice.

Patients And Methods: A total of 75 patients with metastatic colorectal cancer from 8 German medical centers received ≤ 6 administrations of infusional 5-FU according to the AIO (folinate, 5-FU; n = 16), FOLFOX6 (leucovorin calcium [folinic acid], 5-FU, and oxaliplatin; n = 26), or FUFOX (oxaliplatin plus 5-FU/folinic acid; n = 33) regimen.

Progressive multifocal leukoencephalopathy in patients with a hematological malignancy: review of therapeutic options.

In the context of 2 patients with hematological malignancy who developed progressive multifocal leukoencephalopathy (PML), we review the current therapeutic options for this serious complication. Both patients had lymphoma and had been pretreated with the antibody rituximab. Diagnosis of PML was obtained upon the detection of the JC virus.

Successful adoptive transfer and in vivo expansion of haploidentical γδ T cells.

Background: The primary aim of this pilot study was to determine the feasibility and safety of an adoptive transfer and in vivo expansion of human haploidentical γδ T lymphocytes.

Methods: Patients with advanced haematological malignancies who are not eligible for allogeneic transplantation received peripheral blood mononuclear cells from half-matched family donors. For that, a single unstimulated leukapheresis product was incubated with both the anti-CD4 and anti-CD8 antibodies conjugated to paramagnetic particles.

Phase II study of central nervous system (CNS)-directed chemotherapy including high-dose chemotherapy with autologous stem cell transplantation for CNS relapse of aggressive lymphomas.

The prognosis of patients with central nervous system relapse of aggressive lymphoma is very poor with no therapy established so far. In a prospective multicenter phase II study, we evaluated a potentially curative chemotherapy-only regimen in these patients. Adult immunocompetent patients 65 years of age or under received induction chemotherapy with MTX/IFO/DEP (methotrexate 4 g/m(2) intravenously (i.

Primary prophylactic colony-stimulating factors for the prevention of chemotherapy-induced febrile neutropenia in breast cancer patients.

Background: High-dose or dose-intensive cytotoxic chemotherapy often causes myelosuppression and severe neutropenia among cancer patients. Severe neutropenia accompanied by fever, named febrile neutropenia (FN), is the most serious manifestation of neutropenia usually requiring hospitalization and intravenous antibiotics. FN and neutropenia can lead to chemotherapy treatment delays or dose reductions, which potentially compromises the effectiveness of cancer treatment and prospects for a cure.

Tumor-promoting versus tumor-antagonizing roles of γδ T cells in cancer immunotherapy: results from a prospective phase I/II trial.

Emerging evidence suggests that nitrogen-containing bisphosphonates have direct and indirect anticancer effects including immunomodulatory effects. Using in vivo targeting of bisphosphonate-reactive γδ T cells by adding low-dose interleukin-2 to zoledronic acid, we evaluated the safety, pharmacodynamics, and antitumor activity of this immunotherapy approach in 21 adults with advanced malignancies (renal cell carcinoma [RCC], malignant melanoma, and acute myeloid leukemia). A total of 58 treatment cycles were administered and the median number of treatment cycles was 2.

Effects of concurrent topotecan and radiation on 6-month progression-free survival in the primary treatment of glioblastoma multiforme.

Purpose: To report a prospective, randomized, Phase II trial of radiotherapy with and without topotecan for the treatment of glioblastoma.

Patients And Methods: Inclusion criteria were histology of glioblastoma, age <60 years, and Eastern Cooperative Oncology Group status 0-2. Patients were stratified according to recursive partitioning analysis class, center, and enzyme-inducing antiepileptic medication.

Reduction of HLA-DR+ lymphocytes after treatment with enzastaurin in patients with metastatic thyroid cancer.

Background: Cytotoxic anti-tumor agents like methotrexate or cyclophosphamide have been used in the treatment of autoimmune diseases although the exact mechanism of their immunomodulatory function is unclear. By contrast, molecularly targeted anti-tumor agents, such as the serine/threonine kinase inhibitor enzastaurin, have not been evaluated for treatments other than cancer.

Methods: Blood was sampled from patients with metastatic thyroid cancer treated with enzastaurin followed by the combination treatment of enzastaurin and the anti-folate pemetrexed.

Equitoxicity of bolus and infusional etoposide: results of a multicenter randomised trial of the German High-Grade Non-Hodgkins Lymphoma Study Group (DSHNHL) in elderly patients with refractory or relapsing aggressive non-Hodgkin lymphoma using the CEMP regimen (cisplatinum, etoposide, mitoxantrone and prednisone).

To compare toxicity of etoposide bolus with continuous infusion and to assess the efficacy of the CEMP (cisplatinum, etoposide, mitoxantrone, prednisone) regimen, 47 patients with refractory or relapsed aggressive non-Hodgkin's lymphoma older than 60 years (n=43) or not qualifying for high-dose chemotherapy (n=4) received five four-weekly CEMP cycles. Patients were randomised to start with bolus or continuous-infusion etoposide and then received bolus and infusional etoposide in an alternating fashion. The primary objective was the comparison of differences in the course of leukocytopenia and thrombocytopenia between the two application schedules.

Dexamethasone, high-dose cytarabine, and cisplatin in combination with rituximab as salvage treatment for patients with relapsed or refractory aggressive non-Hodgkin's lymphoma.

We designed a multicenter Phase II trial to prospectively evaluate the efficacy and safety of the combination of rituximab with the DHAP regimen (dexamethasone, high-dose cytarabine, cisplatin) in patients who relapsed after or were resistant to a CHOP-like regimen. A total of 53 patients with relapsed or resistant aggressive B-cell NHL were analyzed. The overall response rate was 62.

A CD33-specific single-chain immunotoxin mediates potent apoptosis of cultured human myeloid leukaemia cells.

A novel single-chain immunotoxin was constructed by combining a CD33-specific single chain Fv (scFv) antibody fragment with an engineered variant of Pseudomonas exotoxin A (ETA). The variant toxin carries the KDEL peptide at its C-terminus, a cellular peptide mediating improved retrograde transport to the endoplasmic reticulum. The purified recombinant fusion protein induced potent apoptosis of the human myeloid cell lines U937, HL-60 and THP-1.

Response to chemotherapy and treating institution predict survival in primary central nervous system lymphoma.

The majority of the available data on primary central nervous system lymphoma (PCNSL) derive from small unicentric or oligocentric studies. In this multicentre study, we evaluated the response, survival and toxicity in PCNSL patients after carmustine, methotrexate 1.5 g/m2, procarbazine and dexamethasone (BMPD) chemotherapy and searched for prognostic factors.

Randomized study to evaluate the use of high-dose therapy as part of primary treatment for "aggressive" lymphoma.

Purpose: This trial of the German High-Grade Non-Hodgkin's Lymphoma Study Group compares the use of high-dose therapy (HDT) as part of primary treatment with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) plus etoposide followed by involved-field (IF) radiotherapy in a randomized, multicenter, phase III study.

Patients And Methods: Three hundred twelve patients with "aggressive" non-Hodgkin's lymphoma aged View Article and Find Full Text PDF