Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative option for secondary acute myeloid leukemia (sAML). This study compared haploidentical donor (Haplo), matched sibling donor (MSD), and matched unrelated donor (MUD) HSCT in patients with sAML in first complete remission (CR1). Data from 3862 patients (Haplo = 643, MSD = 715, MUD = 2504) transplanted between 2010 and 2022 were analyzed, with a median follow-up of 3.3 years. Groups differed in patient and donor age, conditioning regimen, stem cell source, and graft-versus-host disease (GVHD) prophylaxis. Multivariate analysis showed that MSD-HSCT had a higher relapse risk than Haplo-HSCT (hazard ratio [HR]: 1.64) but lower non-relapse mortality (NRM, HR: 0.32) and acute GVHD risk (HR: 0.54 for grade II-IV), leading to an overall survival (OS) benefit (HR: 0.76). MUD-HSCT had lower NRM than Haplo-HSCT (HR: 0.63) but there were no significant differences in OS or GVHD risk. Donor type did not impact leukemia-free survival (LFS) or GVHD-free and relapse-free survival (GRFS). Adverse cytogenetics and reduced-intensity conditioning were associated with increased relapse risk, while lower Karnofsky scores, older age, and adverse cytogenetics independently predicted worse NRM, LFS, OS, and GRFS outcomes. Female-to-male donor-recipient pairs had an increased risk of chronic GVHD. In this registry-based analysis, MSD offered the best outcomes for sAML in CR1. Haplo-HSCT was comparable to MUD-HSCT, despite a higher NRM, and achieved long-term disease control in 60% of patients due to a low relapse incidence. In the absence of an MSD, both Haplo and MUD are viable alternatives.

Total body irradiation (TBI) plus chemotherapy is commonly applied prior to allogeneic hematopoietic stem cell transplantation (SCT) for patients with acute lymphoblastic leukemia (ALL). Here, we retrospectively analyzed registry data from the German Multicenter Study Group for Adult ALL (GMALL) and report the outcomes for 111 adult ALL patients who received 8 Gy TBI-based SCT conditioning in first complete remission between 2002 and 2018 after initial treatment with pediatric-based approaches. Patients had a median age of 52 years (range 18-65) at initial diagnosis, and the majority of patients (93%) had a good performance status (ECOG 0/1). 97 patients (87%) showed high-risk features according to GMALL criteria, of whom 58 (60%) were Philadelphia chromosome/BCR::ABL1-positive. With a median follow-up of 3.1 years after SCT, the survival rates at one, three, and five years were 72%, 64%, and 57% for disease-free survival, and 76%, 67%, and 61% for overall survival, respectively. The rates of non-relapse mortality at one, three, and five years were 22%, 26%, and 30%, while the cumulative incidences of relapse were 7%, 10%, and 14%, respectively. In summary, 8 Gy TBI conditioning in ALL patients was feasible and resulted in outcomes similar to those previously reported for 12 Gy conditioning regimens.

Several case series have highlighted the ADVOS hemodialysis system’s efficacy in eliminating water-soluble and protein-bound substances across diverse patient populations, such as multiorgan failure, acute-on-chronic liver failure (ACLF), acidosis, and even COVID-19. The EMOS-Registry, a non-interventional, multi-center patient registry, amassed real-world evidence, culminating in the largest patient cohort treated with ADVOS to date. This study aims to present and analyze the final performance and safety outcomes from the entire dataset comprising 282 participants. Data spanning from January 18, 2017, to August 31, 2020, were collected from five German hospitals, encompassing subsets of patients with acidosis and ACLF grade 3. Performance and safety were assessed through vital signs, clinical laboratory parameters and blood gas analyses. The SOFA Score-Standardized Mortality Ratio (SMR) served to evaluate patient outcomes in the absence of a control group. Participants, with a median age of 58 years, predominantly male (64%), exhibited a high requirement for mechanical ventilation (68%) and vasopressors (82%) with a median SOFA Score of 15. Notably, a median of 3 (IQR 2, 5) ADVOS sessions per patient were administered. Following the initial treatment, significant reductions were observed in bilirubin (−1.9 [CI 95% −1.3, −2.5]), creatinine (−0.5 [−0.4, −0.6]), and blood urea nitrogen (−13.1 mg/dL [−10.3, −16.0]) levels. Moreover, there were marked improvements in blood pH (7.34 vs. 7.41, p < 0.001), HCO3- (19.4 vs. 24.6 mmol/l, p < 0.001) and base excess (−5.6 vs. 0.2 mmol/l, p < 0.001). The observed mortality rate (66%) was notably lower than the expected rate based on SOFA Score (84%), resulting in a SMR of 0.79 (95% CI: 0.66–0.93), with a calculated number needed to treat (NNT) of 5.8. This study emphasizes the ADVOS system’s efficacy in eliminating water-soluble and protein-bound substances and correcting acid-base imbalances across a diverse cohort with multiorgan failure. However, further validation through randomized controlled trials is warranted to solidify these findings.Trial registrationDRKS00017068. Registered 29 April 2019 – Retrospectively registered, https://drks.de/search/en/trial/DRKS00017068

Digital biomarkers show significant potential and are emerging as outcome measures in clinical trials in spastic ataxias (SPAX). Research on the performances of digital biomarkers in home environments remains limited. To evaluate feasibility, user adherence, time-of-day and learning effects, and consistency across settings of the SPAX-app for home monitoring in clinical trials. The app contains four tasks assessing gait, standing balance, and finger and hand movements, along with a patient-reported outcome measure (PROM). We conducted an 8-week long-term study in 38 SPAX patients and 10 healthy controls. Subjects first answered the SPAX-app PROM and performed tasks during one in-clinic session. Severity of ataxia and spasticity were assessed by clinician-reported outcome measures (ClinROs). Subjects then performed the tasks and answered the PROM twice a week in the morning and evening at home. The SPAX-app showed high feasibility for finger and hand movement tasks (92%), but limited feasibility for gait (47%) and stance (63%) tasks. Among those able to perform the tasks, adherence was high (81%). A significant difference (p < 0.01) was found between morning and evening assessments by PROMs in SPAX. Results remained stable across the day and repeated assessments, except for the inter-onset interval in finger tapping (p = 0.002 and p = 0.020, respectively). Strong correlations were observed between tasks performed at home and in the clinic. Motor outcome measures correlated well with ClinROs, but not with PROMs. The SPAX-app is a feasible tool for remote assessment in SPAX, showing high feasibility for finger and hand movement tasks, but limited feasibility for gait and stance tasks at home. Time-of-day and learning effects were minimal. Longer-term studies are needed to assess clinical relevance.

We retrospectively analyzed data from the EBMT registry on patients with pretransplant comorbidities associated with cardiovascular risk. Patients who underwent first allogeneic hematopoietic cell transplantation for acute myeloid leukemia in first complete remission between 2010 and 2022 from unrelated donors using post-transplant cyclophosphamide (ptCy) or anti-thymocyte globulin (ATG)-based graft-versus-host disease prophylaxis with a history of cardiac disease, arrhythmia, diabetes, obesity or cerebrovascular disease according to the HCT-specific comorbidity index were included. We performed a matched-pair analysis using a propensity score. After matching, 432 patients were included: 313 in the ATG group and 119 in the ptCy group. At 2 years, overall survival was 67.5% (95% CI 61-73.2) and 68.6% (95% CI 56.7-77.8); leukemia-free survival was 60.4% (95% CI 53.8-66.4) and 62.6% (95% CI 50.4-72.6); relapse incidence was 22.1% (95% CI 17-27.7) and 23.2% (95% CI 14.3-33.4); non-relapse mortality was 17.5% (95% CI 13.1-22.4) and 14.1% (95% CI 7.5-22.8), respectively. In conclusion, our study suggests that the use of ptCY for GVHD prophylaxis in patients with preexisting comorbidities associated with cardiovascular risk yields long-term outcomes comparable to those observed with ATG-based approaches.

Anatomic imaging of renal masses provides limited information on the histology or likely aggressiveness of the tumor, leading to the use of invasive procedures such as renal mass biopsy or empiric partial or radical nephrectomy. Molecular imaging can assist in risk stratification of indeterminate renal masses, potentially contributing to optimal patient decision-making. Two primary approaches have been explored for renal mass molecular imaging. The first is the use of agents that target carbonic anhydrase IX (CAIX), a cell-surface protein that is over-expressed on clear cell renal cell carcinoma (ccRCC) and generally not expressed on other renal tumors. A recent phase III trial (ZIRCON) is widely believed to have laid the groundwork for United States Food and Drug Administration approval of the CAIX monoclonal antibody 89Zr-girentuximab. The second approach is the use of mitochondrial imaging agents, most notably 99mTc-sestamibi, which are lipophilic cations that accumulate in tumors with an abundance of mitochondria with negative charge potential (e.g., oncocytomas and other benign/indolent lesion) and do not accumulate in tumors with multidrug resistance pumps (e.g., ccRCC). The complementary information from 89Zr-girentuximab and 99mTc-sestamibi can provide improved risk stratification. Further, emerging new targeted radiotracers and techniques such as imaging biomarker discovery with artificial intelligence will bolster those concepts. In this manual, we synthesize key data into a recommended approach.

Patient safety (PaSi) is no longer understood as merely the prevention of adverse events, but rather as all activities aimed at ensuring asafe care environment and aculture of patient safety. PaSi is considered one of the most pressing goals in healthcare. Consequently, alarge number of stakeholders in joint self-administration in Germany are now working to improve PaSi. The methods used to determine PaSi range from patient surveys and voluntary reports by healthcare providers using critical incident reporting systems (CIRS) to analyses of medical records and routine data, while the search for the prerequisites for safe care makes use of classic quality management methods. Evaluation results from Germany indicate that most PaSi incidents (PSI) remain undetected and that there is still agreat need for research to investigate PSI incidences, determinants of PSI, and interventions to prevent PSI as well as to create aPaSi culture.