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Infectious complications after allogeneic haematopoietic stem cell transplantation (allo-HCT) remain a clinical challenge. This is a guideline provided by the AGIHO (Infectious Diseases Working Group) of the DGHO (German Society for Hematology and Medical Oncology). A core group of experts prepared a preliminary guideline, which was discussed, reviewed, and approved by the entire working group. The guideline provides clinical recommendations for the preventive management including prophylactic treatment of viral, bacterial, parasitic, and fungal diseases. The guideline focuses on antimicrobial agents but includes recommendations on the use of vaccinations. This is the updated version of the AGHIO guideline in the field of allogeneic haematopoietic stem cell transplantation utilizing methods according to evidence-based medicine criteria.

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.

Catheter-related infections (CRI) cause considerable morbidity in hospitalized patients. The incidence does not seem to be higher in neutropenic patients than in nonneutropenic patients. Gram-positive bacteria (coagulase-negative staphylococci, Staphylococcus aureus) are the pathogens most frequently cultured, followed by Candida species. Positive blood cultures are the cornerstone in the diagnosis of CRIs, while local signs of infection are not necessarily present. Blood cultures should be taken from peripheral blood and from the venous catheter. A shorter time to positivity of catheter blood cultures as compared with peripheral blood cultures supports the diagnosis of a CRI. In many cases, a definite diagnosis requires catheter removal and microbiological analysis. The role plate method with semiquantitative cultures has been established as standard in most laboratories. Antimicrobial treatment of CRI should be directed by the in vitro susceptibility of the isolated pathogen. Primary removal of the catheter is mandatory in S. aureus and Candida infections, as well as in case of tunnel or pocket infections. Future studies will elucidate whether the rate of CRI in neutropenic patients may be reduced by catheters impregnated with antimicrobial agents.

Patients with haematological malignancies and prolonged periods of neutropenia after chemotherapy are at high risk for severe bacterial and fungal infections. Those infections have long time been considered as a contraindication for subsequent haematopoietic stem cell transplantation (HCT). We conducted a prospective, non-randomized study of granulocyte transfusions (GTX) to control acute life-threatening infections (44 episodes) and to prevent recurrence of severe fungal infections during HCT or intensive chemotherapy (23 episodes). GTX achieved control in 82% (36/44) of acute life-threatening infections. No single reactivation of a previous infection occurred under prophylactic GTX (0/23). Median survival was 170 days in the interventional group and 185 days in the prophylactic group; death in both patient groups was mainly due to underlying progressive malignant disease. We conclude that under GTX, the infection-related mortality even in high-risk patients is low. Due to a secondary prophylaxis with GTX, haematopoietic allografts can be safely given to patients with previous fungal infections.

In a pilot study high-dose melphalan (HD-Mel, 200 mg/m2) and autologous stem cell transplantation (ASCT) were administered to 14 patients (median age 52, range 29-60 years) with acute myeloid leukaemia (AML) in first relapse after a previous ASCT in first complete remission (n=11) or chemotherapy (n=3). A first cohort of five patients received HD-Mel as salvage therapy after a previous cycle of mitoxantrone, topotecan and cytarabine (MTC) had failed in four out of five patients, while a second cohort of nine patients received HD-Mel in untreated relapse. Thirteen (93%) of 14 patients achieved a second complete remission (CR2), including all four patients who had been refractory to MTC. No treatment-related mortality was observed after HD-Mel. Thirteen (93%) patients were able to proceed to a dose-reduced allogeneic stem cell transplantation (allo-SCT) from human-leucocyte-antigens-compatible unrelated (n=12) or sibling donors (n=1) in CR2 (n=11) or poor recovery/relapse (n=2) after a median of 2 (1.7-4.5) months following HD-Mel. Three MTC-refractory patients, but none of the upfront HD-Mel patients, died due to an allograft-related non-relapse cause. Nine patients are alive in CR2 after a median of 6 (2-49) months after HD-Mel and a median of 4 (0.6-47) months after a sequential allo-SCT. Although median follow-up is still short, the proportion of patients achieving a CR2, as well as of those proceeding to a subsequent reduced-intensity-conditioning-allo-SCT, is superior to those previously reported. Our results highly encourage to further investigate HD-Mel and ASCT as a promising salvage regimen for relapsed AML patients for whom autologous peripheral blood stem cells are available.