Spectrum and functional validation of PSMB5 mutations in multiple myeloma.

Despite an increasing number of approved therapies, multiple myeloma (MM) remains an incurable disease and only a small number of patients achieve prolonged disease control. Some genes have been linked with response to commonly used anti-MM compounds, including immunomodulators (IMiDs) and proteasome inhibitors (PIs). In this manuscript, we demonstrate an increased incidence of acquired proteasomal subunit mutations in relapsed MM compared to newly diagnosed disease, underpinning a potential role of point mutations in the clonal evolution of MM.

Anti-infective vaccination strategies in patients with hematologic malignancies or solid tumors-Guideline of the Infectious Diseases Working Party (AGIHO) of the German Society for Hematology and Medical Oncology (DGHO).

Infectious complications are a significant cause of morbidity and mortality in patients with malignancies specifically when receiving anticancer treatments. Prevention of infection through vaccines is an important aspect of clinical care of cancer patients. Immunocompromising effects of the underlying disease as well as of antineoplastic therapies need to be considered when devising vaccination strategies.

Oncogene-induced senescence: a potential breakpoint mechanism against malignant transformation in plasma cell disorders.

Oncogene-induced senescence (OIS) is a cellular tumor-suppressive mechanism present in several premalignant conditions. Here, we analyze the possible impact of OIS on malignant transformation in plasma cell disorders. Tumor samples from 125 patients with different disease stages were analyzed immunohistochemically for expression of senescence markers.

Analysis of long-term survival in multiple myeloma after first-line autologous stem cell transplantation: impact of clinical risk factors and sustained response.

The widespread use of high-dose therapy and autologous stem cell transplantation (ASCT) as well as the introduction of novel agents have significantly improved outcomes in multiple myeloma (MM) enabling long-term survival. We here analyze factors influencing survival in 865 newly diagnosed MM patients who underwent first-line ASCT at our center between 1993 and 2014. Relative survival and conditional survival were assessed to further characterize long-term survivors.

Primary prophylaxis of invasive fungal infections in patients with haematological malignancies: 2017 update of the recommendations of the Infectious Diseases Working Party (AGIHO) of the German Society for Haematology and Medical Oncology (DGHO).

Immunocompromised patients are at high risk of invasive fungal infections (IFI), in particular those with haematological malignancies undergoing remission-induction chemotherapy for acute myeloid leukaemia (AML) or myelodysplastic syndrome (MDS) and recipients of allogeneic haematopoietic stem cell transplants (HSCT). Despite the development of new treatment options in the past decades, IFI remains a concern due to substantial morbidity and mortality in these patient populations. In addition, the increasing use of new immune modulating drugs in cancer therapy has opened an entirely new spectrum of at risk periods.

Isavuconazole shortens the QTc interval.

Isavuconazole is a novel antifungal drug approved for the treatment of adults with invasive aspergillosis and mucormycosis. While azoles as a class effect are known to prolong QTc interval, clinical trials have shown that isavuconazole administration may cause shortening in a dose-related manner. Here, we assessed the effects of isavuconazole on the length of QTc interval.

Respiratory syncytial virus A in haematological patients with prolonged shedding: Premature stop codons and deletion of the genotype ON1 72-nucleotide-duplication in the attachment G gene.

Background: Respiratory syncytial virus (RSV) can be associated with severe disease and prolonged shedding in immunocompromised patients.

Objective: To investigate the genetic variability of RSV in consecutive samples of haematological patients with prolonged RSV shedding.

Study Design: Haematological patients at the University Hospital Heidelberg are routinely screened for respiratory viruses during winter season.

Pretransplant Vitamin D Deficiency Is Associated With Higher Relapse Rates in Patients Allografted for Myeloid Malignancies.

Purpose Vitamin D (VitD) deficiency is common in patients with hematologic malignancies undergoing allogeneic transplantation (alloSCT), but its prognostic relevance is unclear. Patients and Methods The impact of pretransplant VitD status on overall survival, relapse mortality, and nonrelapse mortality was investigated retrospectively in a cohort of 492 patients undergoing alloSCT at our center from 2002 to 2013. VitD deficiency was defined as a serum level of 25-hydroxyvitamin D3 < 20 ng/mL (equivalent to < 50 nM) before alloSCT and was assessed using accredited laboratory methods and a standard chemiluminescent immunoassay.

The influence of rituximab-containing chemotherapy on HCV load in patients with HCV-associated non-Hodgkin's lymphomas.

Efficacy and safety of rituximab treatment in patients with Hepatitis C virus (HCV) infection associated non-Hodgkin's lymphoma (NHL) are still disputable. The aim of this study was to evaluate the influence of rituximab-containing chemotherapy on HCV load. Fifty-four patients with both HCV infection and NHL were identified between 2000 and 2016 at our institution.

Molecular signaling in multiple myeloma: association of RAS/RAF mutations and MEK/ERK pathway activation.

Multiple myeloma (MM) is a plasma cell malignancy that is still considered to be incurable in most cases. A dominant mutation cluster has been identified in RAS/RAF genes, emphasizing the potential significance of RAS/RAF/MEK/ERK signaling as a therapeutic target. As yet, however, the clinical relevance of this finding is unclear as clinical responses to MEK inhibition in RAS-mutant MM have been mixed.

Analysis of prognostic factors in patients with newly diagnosed diffuse large B-cell lymphoma and skeletal involvement.

Background: Skeletal involvement (SI) is observed at low prevalence in patients with diffuse large B-cell lymphoma (DLBCL). Due to the rareness of this particular condition, prospective trials for these patients are scarce.

Methods: We analyzed clinical characteristics and outcome of 75 patients with DLBCL and SI in order to identify factors with prognostic impact towards progression-free survival (PFS) and overall survival (OS).

Influenza virus infections in patients with malignancies -- characteristics and outcome of the season 2014/15. A survey conducted by the Infectious Diseases Working Party (AGIHO) of the German Society of Haematology and Medical Oncology (DGHO).

Influenza virus infections (IVI) may pose a vital threat to immunocompromised patients such as those suffering from malignancies, but specific data on epidemiology and outcome in these patients are scarce. In this study, we collected data on patients with active cancer or with a history of cancer, presenting with documented IVI in eight centres in Germany. Two hundred and three patients were identified, suffering from haematological malignancies or solid tumours; 109 (54 %) patients had active malignant disease.

Community acquired respiratory virus infections in cancer patients-Guideline on diagnosis and management by the Infectious Diseases Working Party of the German Society for haematology and Medical Oncology.

Background: Community acquired viruses (CRVs) may cause severe disease in cancer patients. Thus, efforts should be made to diagnose CRV rapidly and manage CRV infections accordingly.

Methods: A panel of 18 clinicians from the Infectious Diseases Working Party of the German Society for Haematology and Medical Oncology have convened to assess the available literature and provide recommendations on the management of CRV infections including influenza, respiratory syncytial virus, parainfluenza virus, human metapneumovirus and adenovirus.

Management of high-risk Myeloma: an evidence-based review of treatment strategies.

Introduction: Despite the progress made in the treatment of patients with multiple myeloma over recent decades, a significant cohort with high-risk disease as defined by specific clinical and genetic criteria continue to respond poorly to standard treatment. These patients represent a particular challenge to the treating physician and require early identification as well as personalized treatment strategies.

Areas Covered: In this review, we discuss the prognostic impact of adverse clinical, radiological and genetic factors, evaluate available scoring systems and highlight key aspects of the therapeutic management of high-risk myeloma.

Analysis of clinical characteristics and outcome of patients with previously untreated diffuse large B-cell lymphoma and renal involvement in the rituximab era.

Renal involvement in patients with lymphoma is rare but associated with poor prognosis. We analyzed characteristics and outcome of 22 patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) and renal involvement treated with a rituximab-containing regimen in curative intent. The majority of patients presented in advanced disease, 86% were Ann Arbor stage ≥ III and had an IPI score ≥ 3.

The influence of rituximab, high-dose therapy followed by autologous stem cell transplantation, and age in patients with primary CNS lymphoma.

For patients with diffuse large B cell lymphoma without the involvement of the CNS, the addition of rituximab to standard chemotherapy has significantly improved survival. In this single-center, retrospective analysis, a total of 81 primary CNS lymphoma (PCNSL) patients treated in our institution between 2000 and 2011 were included. Beside first-line chemotherapy with or without rituximab, we evaluated the impact of age (≤/>60 years), autologous stem cell transplantation (ASCT +/-), and other factors upon overall survival (OS) and progression-free survival (PFS).

CT-morphological characterization of respiratory syncytial virus (RSV) pneumonia in immune-compromised adults.

Purpose: Characterization and follow-up evaluation of chest CT of RSV pneumonia in immune-compromised adults during a seasonal epidemic.

Materials And Methods: Retrospective analysis of 132 chest CT examinations of 51 adult immune-compromised patients (29 m/22f, Ø58 years) with clinical signs of pneumonia and positive RSV test in winter 2011/2012. Two experienced chest radiologists evaluated the morphology (bronchial wall thickening, tree-in-bud, nodules, halo, ground-glass opacities, consolidations, pleural fluid) of the CT scans by consensus.

Expression of Mucin-1 in multiple myeloma and its precursors: correlation with glycosylation and subcellular localization.

Aims: Recent reports suggest a possible role for extracellular (MUC1N) and transmembrane (MUC1C) subunits of Mucin 1 (MUC1) in the pathogenesis of multiple myeloma (MM). Nuclear translocation of MUC1C is involved in activation of various oncogenic signalling pathways and both MUC1 subunits are potential therapeutic targets. We aimed at performing a comprehensive expression analysis of the MUC1 subunits in plasma cell dyscrasias.

Progression in smoldering myeloma is independently determined by the chromosomal abnormalities del(17p), t(4;14), gain 1q, hyperdiploidy, and tumor load.

Purpose: The aim of this study was to analyze chromosomal aberrations in terms of frequency and impact on time to progression in patients with smoldering multiple myeloma (SMM) on the background of clinical prognostic factors.

Patients And Methods: The chromosomal abnormalities 1q21, 5p15/5q35, 9q34, 13q14.3, 15q22, 17p13, t(11;14)(q13;q32), and t(4;14)(p16.

Risk factors and containment of respiratory syncytial virus outbreak in a hematology and transplant unit.

Respiratory syncytial virus (RSV) usually causes self-limiting upper respiratory tract infections, but can be associated with severe lower respiratory tract infection disease (LRTID) in infants and in patients with hematologic malignancies. We have analyzed the risk factors and the measures for containment within an outbreak of nosocomial RSV infections in a hematology and SCT unit. A total of 56 patients were affected (53 RSV-A and 3 RSV-B) including 32 transplant patients (16 allogeneic and 16 autologous).

Changes in severity of influenza A(H1N1)pdm09 infection from pandemic to first postpandemic season, Germany.

We studied risk factors for a severe clinical outcome in hospitalized patients with laboratory-confirmed influenza A(H1N1)pdm09 infection at the University Hospital Heidelberg in the pandemic and first postpandemic seasons. We identified 102 patients in 2009-10 and 76 in 2010-11. The proportion of severely diseased patients dramatically increased from 14% in 2009-10 to 46% in 2010-11 as did the mortality rate (5%-12%).