SummaryA phase 2 trial was performed to study the combination of bortezomib (VELCADEÒ) 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 1AE3 mg/m 2 on days 1, 4, 8, and 11, followed by three 5-week cycles with bortezomib 1AE3 mg/m 2 on days 1, 8, 15, and 22. Within all cycles, DEX 20 mg/d was given orally on the day of bortezomib injection and the day thereafter. In addition, patients received CY continuous oral treatment at a dose of 50 mg/d p.o. once daily. Fifty patients completing at least one treatment cycle were evaluable for response. Complete, partial, and minor responses occurred in 16%, 66% and 8% of patients, respectively; overall response rate 90% (efficacy analysis). Median event-free survival was 12 months, with a median overall survival of 22 months. Adverse events (AE) of grades 3 or 4 occurring in at least 10% of patients comprised leucopenia, infection, herpes zoster, thrombocytopenia, neuropathy and fatigue. Bortezomib combined with DEX and CY is a highly effective treatment for relapsed MM at an acceptable rate of grade 3/4 AE. Antiviral prophylaxis appears to be mandatory.

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© F e r r a t a S t o r t i F o u n d a t i o nO IntroductionThe rising incidence of invasive fungal infections, especially invasive aspergillosis, compromises therapeutic outcomes in hematologic cancer patients and in transplant recipients. [1][2][3][4][5] The utilization of newly introduced antifungal agents clearly improved the tolerability of patients combating severe underlying diseases. 6,7 Despite better outcome in primary treatment of invasive aspergillosis in comparison to conventional amphotericin B, response and survival require further improvement. 8,9 Additionally, early diagnosis of invasive fungal infections is critical.10 But usually diagnosis is delayed and thus hampers further treatment outcome. 11Therefore, the prevention of invasive fungal infections upfront has become the major goal in patient care in high-risk patient populations. Since the first edition of these recommendations regarding antifungal prophylaxis, close to 20 relevant publications have been added to the field, necessitating an updated review of their impact on clinical decision making. 12 On the other hand new meta-analyses on prophylaxis of invasive fungal infections have also been published, but do not differentiate between specific patient populations and risk factors. 13,14 To maintain comparability with the previous recommendation, the EBM criteria proposed by the Infectious Diseases Society of America (IDSA) are again employed throughout this document (Table 1). 15 Several newly introduced antifungal agents have been utilized in prophylaxis for the first time. These and other new studies have been incorporated into this updated guideline of the Infectious Diseases Working Party (AGIHO) of the German Society for Haematology and Oncology. The aim of this review is to provide the treating physician an up-to-date tool for the daily bedside decisions on primary antifungal prophylaxis. Objectives of antifungal prophylaxisIt is evident that the most relevant endpoint of antifungal prophylaxis is the reduction of mortality. However, death attributable to invasive fungal infection is difficult to prove and a reduction in overall mortality as a desirable endpoint of any clinical decision is difficult to achieve in the context of multiple competing illnesses in a severely immunocompromised host. Thus usually the reduction of the incidence rate of breakthrough invasive fungal infection is chosen as the primary endpoint of clinical trials. Improving rates of mucosal or other superficial infection and reducing colonization are no proper endpoints for antifungal prophylaxis with systemically active compounds. Design and MethodsThe guideline was prepared by a group of German clinicians. Systematic literature search comprised Medline, CancerLit, Embase, Cochrane Library and conference proceedings of Advances Against Aspergillosis, ASH, EBMT, ECCMID, ESMO, Focus on Fungal Infections, and ICAAC/IDSA, yielding a total of 86 clinical trials comprising 16,922 patients. Data extracted by OAC and MSi from each clinical study identifie...

The Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO) here presents its updated recommendations for the treatment of documented fungal infections. Invasive fungal infections are a main cause of morbidity and mortality in cancer patients undergoing intensive chemotherapy regimens. In recent years, new antifungal agents have been licensed, and agents already approved have been studied in new indications. The choice of the most appropriate antifungal treatment depends on the fungal species suspected or identified, the patient’s risk factors (e.g., length and depth of neutropenia), and the expected side effects. This guideline reviews the clinical studies that served as a basis for the following recommendations. All recommendations including the levels of evidence are summarized in tables to give the reader rapid access to the information.

Cancer patients frequently require central venous catheters for therapy and parenteral nutrition and are at high risk of central venous catheter–related infections (CRIs). Moreover, CRIs prolong hospitalization, cause an excess in resource utilization and treatment cost, often delay anti-cancer treatment, and are associated with a significant increase in mortality in cancer patients. We therefore summoned a panel of experts by the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO) and updated our previous guideline on CRIs in cancer patients. After conducting systematic literature searches on PubMed, Medline, and Cochrane databases, video- and meeting-based consensus discussions were held. In the presented guideline, we summarize recommendations on definition, diagnosis, management, and prevention of CRIs in cancer patients including the grading of strength of recommendations and the respective levels of evidence. This guideline supports clinicians and researchers alike in the evidence-based decision-making in the management of CRIs in cancer patients.