A sequential regimen of chemotherapy, reduced-intensity conditioning (RIC) for allogeneic stem cell transplantation (SCT), and prophylactic donor lymphocyte transfusion (pDLT) was studied in 103 patients with refractory acute myeloid leukemia (AML). According to published criteria, refractoriness was defined by primary induction failure (PIF; n ‫؍‬ 37), early (n ‫؍‬ 53), refractory (n ‫؍‬ 8), or second (n ‫؍‬ 5) relapse. Chemotherapy consisted of fludarabine (4 ؋ 30 mg/m 2 ), cytarabine (4 ؋ 2 g/m 2 ), and amsacrine (4 ؋ 100 mg/ m 2 ), followed 4 days later by RIC, comprising 4 Gy total body irradiation (TBI), cyclophosphamide, and antithymocyte globulin. Patients without graft-versus-host disease (GvHD) at day ؉120 received pDLT in escalating doses. Patients' median age was 51.8 years. Before conditioning, 99 patients had active disease, 3 were aplastic, 1 was in second complete remission (CR2). Forty-one patients had family donors, 62 had unrelated donors. With a 25-month median follow-up, overall survival (OS) at 1, 2, and 4 years was 54%, 40%, and 32%; the respective leukemiafree survival (LFS) was 47%, 37%, and 30%. Patients with PIF showed a 2-year OS of 62.5%. OS was 87% in 17 patients receiving pDLT. One-year cumulative incidence of leukemic death and non-relapsemortality was 28.7% and 17.2%. In a multivariate analysis, more than 2 courses of prior chemotherapy were the strongest predictor for poor outcome (P ‫؍‬ .007; HR ‫؍‬ 3.01 [OS]; P ‫؍‬ .002; HR ‫؍‬ 3.25 [LFS]). These results indicate a high activity of the regimen in refractory AML.

Fever may be the only clinical symptom at the onset of infection in neutropenic cancer patients undergoing myelosuppressive chemotherapy. A prompt and evidence-based diagnostic and therapeutic approach is mandatory. A systematic search of current literature was conducted, including only full papers and excluding allogeneic hematopoietic stem cell transplant recipients. Recommendations for diagnosis and therapy were developed by an expert panel and approved after plenary discussion by the AGIHO. Randomized clinical trials were mainly available for therapeutic decisions, and new diagnostic procedures have been introduced into clinical practice in the past decade. Stratification into a high-risk versus low-risk patient population is recommended. In high-risk patients, initial empirical antimicrobial therapy should be active against pathogens most commonly involved in microbiologically documented and most threatening infections, including Pseudomonas aeruginosa, but excluding coagulase-negative staphylococci. In patients whose expected duration of neutropenia is more than 7 days and who do not respond to first-line antibacterial treatment, specifically in the absence of mold-active antifungal prophylaxis, further therapy should be directed also against fungi, in particular Aspergillus species. With regard to antimicrobial stewardship, treatment duration after defervescence in persistently neutropenic patients must be critically reconsidered and the choice of anti-infective agents adjusted to local epidemiology. This guideline updates recommendations for diagnosis and empirical therapy of fever of unknown origin in adult neutropenic cancer patients in light of the challenges of antimicrobial stewardship.Electronic supplementary materialThe online version of this article (doi:10.1007/s00277-017-3098-3) contains supplementary material, which is available to authorized users.

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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...

Morbidity and mortality in patients with malignancies are increased by viral infections. These mostly are reactivations of asymptomatic latent infections. They primarily concern clinical entities associated with the reactivation of herpes viruses, such as varicella zoster virus (VZV) and cytomegalovirus (CMV). Respiratory tract infections caused by influenza, parainfluenza or respiratory syncytial virus (RSV) are less common. Since reactivation of latent infections has major clinical impact, antiviral prophylaxis is an attractive approach for patients expecting immunosuppression. The main risk factor for clinically relevant reactivation is profound disruption of cellular immune response. Duration and severity of chemotherapy induced neutropenia are of lesser importance. The risk of viral complications rises significantly in the presence of sustained suppression of T-cell function, e.g. in recipients of allogeneic stem cell transplants or of alemtuzumab (Campath-1H) antibody therapy. The objective of this guideline is to review the basis of prophylactic strategies and to provide recommendations for clinicians treating patients with haematological malignancies and solid tumors.