We performed a study to find out how advances in modern medicine have improved the mortality risk of allogeneic stem cell transplantation. We analyzed major transplantation outcome parameters in adult patients on the European Society for Blood and Marrow Transplantation (EBMT) registry who had hematologic malignancies and had received transplants from matched sibling donors. We performed multivariate analyses using the Cox proportional-hazards model including known risk factors for nonrelapse mortality and a matched-pairs analysis. We identified 38 800 patients who fulfilled the inclusion criteria. Considerable changes in patient characteristics have occurred in the past decades, such as older age, different underlying diseases, and a higher proportion of patients with advanced disease. Major reasons for transplantation-related death in the 1980s were infectious complications and graft-versus-host disease. Nonrelapse mortality, measured at 1 year after transplantation, has decreased over time: 29.7% from 1980 through 1989, 24.4% from 1990 through 1999, 14.8% from 2000 through 2009, and 12.2% from 2010 through 2016. On multivariate analysis, the year of transplantation was associated with reduced nonrelapse mortality (P < .0001; hazard ratio [HR] [95% confidence interval (CI)], 0.8 [0.79-0.82], for 5-year intervals) and decreased overall mortality (P < .0001; HR [95% CI], 0.87 [0.86-0.88]. In the matched-pairs analysis of 3718 patients in each group, nonrelapse mortality at 1 year was 24.4% in the 1990s and 9.5% from 2013 through 2016 (P < .0001; HR [95% CI], 0.39 [0.34-0.43]). Transplantation-related mortality has decreased significantly in the past 40 years. These favorable data facilitate evidence-based treatment decisions on transplantation indications in the context of the availability of novel immunotherapies.

Acute myeloid leukemia (AML) is a malignant disorder derived from neoplastic myeloid progenitor cells characterized by abnormal proliferation and differentiation. Although novel therapeutics have recently been introduced, AML remains a therapeutic challenge with insufficient cure rates. In the last years, immune-directed therapies such as chimeric antigen receptor (CAR)-T cells were introduced, which showed outstanding clinical activity against B-cell malignancies including acute lymphoblastic leukemia (ALL). However, the application of CAR-T cells appears to be challenging due to the enormous molecular heterogeneity of the disease and potential long-term suppression of hematopoiesis. Here we report on the generation of CD33-targeted CAR-modified natural killer (NK) cells by transduction of blood-derived primary NK cells using baboon envelope pseudotyped lentiviral vectors (BaEV-LVs). Transduced cells displayed stable CAR-expression, unimpeded proliferation, and increased cytotoxic activity against CD33-positive OCI-AML2 and primary AML cells in vitro. Furthermore, CD33-CAR-NK cells strongly reduced leukemic burden and prevented bone marrow engraftment of leukemic cells in OCI-AML2 xenograft mouse models without observable side effects.

Patients with haematological malignancies (HM) are at high risk of developing invasive fungal disease (IFD) with high morbidity and attributable mortality. We reviewed data published until September 2021 to update the 2017 antifungal prophylaxis recommendations of the German Society of Haematology and Medical Oncology (DGHO). The strong recommendation to administer antifungal prophylaxis in patients with HM with long-lasting neutropenia, i.e. 7 days remains unchanged. Posaconazole remains the drug of choice for mould-active prophylaxis in these patients. Novel treatment options in HM, such as CAR-T-cell treatment or novel targeted therapies for acute myeloid leukaemia (AML) were considered, however, data are insufficient to give general recommendations for routine antifungal prophylaxis in these patients. Major changes regarding specific recommendations compared to the 2017 edition are the now moderate instead of mild support for the recommendations of isavuconazole and voriconazole. Furthermore, published evidence on micafungin allows recommending it at moderate strength for its use in HM. For the first time we included recommendations for non-pharmaceutical measures regarding IFD, comprising the use of high-efficiency particulate air (HEPA) filters, smoking, measures during construction work and neutropenic diets.We reviewed the impact of antifungal prophylaxis with triazoles on drug–drug interactions with novel targeted therapies that are metabolized via cytochrome p450 where triazoles inhibit CYP3A4/5. The working group recommends reducing the dose of venetoclax when used concomitantly with strong CYP3A4 inhibiting antifungals. Furthermore, we reviewed data on the prophylactic use of novel antifungal agents. Currently there is no evidence to support their use in a prophylactic setting in clinical practice.