TaKeTiNa Music Therapy for Outpatient Treatment of Depression: Study Protocol for a Randomized Clinical Trial.

BACKGROUND/OBJECTIVES: Depression is a prevalent and debilitating illness that significantly affects psychological and physical well-being. Apart from conventional therapies such as psychotherapy and medication, individuals with depression often lack opportunities for activities that are generally perceived as enjoyable, such as music, meditation, and arts, which have demonstrated therapeutic effectiveness. TaKeTiNa music therapy has been employed as a therapeutic intervention for more than two decades. However, there is a notable absence of well-designed clinical trials investigating its antidepressant effects, a gap we aim to address in our current study. Furthermore, shifts in the progression of depression may manifest both psychologically, by influencing emotional states, and physiologically, by leading to alterations in lipid and sphingolipid metabolism, cortisol levels, and immune system function. Our study seeks to analyze the impact of TaKeTiNa music therapy on both levels. METHODS: This is a prospective monocentric randomized waitlist-controlled clinical trial. It investigates the influence of TaKeTiNa music therapy on patients with major depression in an outpatient setting. Therefore, interested persons are randomly assigned to two groups, an intervention group or a control group, after completing a screening procedure. The intervention group starts with an eight-week TaKeTiNa music therapy intervention. The waiting group receives the same therapy program after completing the follow-up period. Blood and saliva sampling as well as responses to questionnaires are obtained at specific time points. DISCUSSION: Our study investigates the effects of TaKeTiNa music therapy, a non-pharmacological antidepressant treatment option, on depressive symptoms. We also address functional and causal immunological changes; hormonal changes, such as changes in cortisol levels; and metabolic changes, such as changes in serum lipids and sphingolipids, during the course of depression. We expect that this study will provide evidence to expand the range of treatment options available for depression.

Adjuvant Treatment with S-1 in Patients after R0-Resection of Adenocarcinoma of the Stomach and Esophagogastric Junction: A Multicenter Phase I/II Feasibility Study (GMBH-STO-0114).

INTRODUCTION: S-1 has been shown to be an effective adjuvant treatment option for East Asian patients who underwent gastrectomy for stage II/III gastric cancer. We conducted a phase I/II study to evaluate the feasibility, tolerability, and efficacy of administering S-1 in the adjuvant setting after R0-resection of adenocarcinoma of the stomach and esophagogastric junction (EGJ) in Caucasian patients. METHODS: In this single-cohort, open-label, phase I/II trial, we enrolled patients with locally advanced adenocarcinoma of the stomach or EGJ having undergone R0-resection with or without neoadjuvant treatment. One treatment cycle consisted of oral S-1 (30 mg/m2 bid) for 14 days. Cycles were repeated every 3 weeks for 18 cycles (54 weeks). Primary endpoint was feasibility and tolerability. Safety was evaluated according to the Common Toxicity Criteria Adverse Events (CTCAE) version 4.0. Secondary endpoints were 1-year relapse-free survival (RFS) rate, RFS, and overall survival (OS). RESULTS: Between October 2015 and February 2018, 32 patients were enrolled in 12 German centers, and 30 started adjuvant study treatment. Seventeen patients completed all 18 cycles. Two patients terminated study treatment early due to adverse events (AEs), 7 due to patient's or investigator's decision, and 4 due to recurrence or distant metastasis during adjuvant therapy. Dose levels were reduced to 25 mg/m2 in 9 patients and to 20 mg/m2 in 1 patient. Of patients completing all 18 cycles, 5 did so with reduced dosage of S-1. Documented grade ≥3 AEs were neutropenia, diarrhea, vomiting, polyneuropathy, palmar-plantar erythrodysaesthesia, and rash. Serious AEs were observed in 7 patients. Median RFS was 32.2 months. One-year RFS rate was 77%. Data on OS were still premature at the end of the study. CONCLUSION: Adjuvant treatment with S-1 for 1 year is a feasible and safe treatment option for Caucasian patients diagnosed with gastric adenocarcinoma or cancer of the EGJ after R0-resection.

Radiation therapy of breast cancer in the Nahe Breast Center: first results of an analysis in the context of health services research.

BACKGROUND: The first evaluation of radiotherapy results in patients with breast cancer treated as part of a multimodal oncologic therapy in the Nahe Breast Center is presented. Analysis of the results was performed using an in-practice registry. PATIENTS AND METHODS: From September 2016 to December 2017, 138 patients (median age 62.5 years; range 36-94 years) with breast cancer (right side, n = 67; left side, n = 71) received adjuvant radiation therapy. Of these, 103 patients received gyneco-oncologic care at the Nahe Breast Center, and 35 were referred from outside breast centers. The distribution into stages was as follows: stage I, n = 48; stage II, n = 68; stage III, n = 19; stage IV, n = 3. Neoadjuvant chemotherapy was given to 19 and adjuvant chemotherapy to 50 patients. Endocrine treatment was given to 120 patients. Both 3D conformal (n = 103) and intensity-modulated (n = 35) radiotherapy were performed with a modern linear accelerator. RESULTS: With a median follow-up of 60 months (1-67), local recurrence occurred in 4/138 (2.9%) and distant metastasis in 8/138 (5.8%) patients; 7/138 (5.1%) patients died of their tumors during the follow-up period. The actuarial 5­year local recurrence-free survival of all patients was 97.1%, and the actuarial 5­year overall survival of all patients was 94.9%. We observed no grade 3 or 4 radiogenic side effects. CONCLUSION: The results of radiotherapy for breast carcinoma at the Nahe Breast Center are comparable to published national and international results. In particular, the local recurrence rates in our study, determined absolutely and actuarially, are excellent, and demonstrate the usefulness of radiotherapy.

Relaxed Dot Plots: Faithful Visualization of Samples and Their Distribution.

We introduce relaxed dot plots as an improvement of nonlinear dot plots for unit visualization. Our plots produce more faithful data representations and reduce moiré effects. Their contour is based on a customized kernel frequency estimation to match the shape of the distribution of underlying data values. Previous nonlinear layouts introduce column-centric nonlinear scaling of dot diameters for visualization of high-dynamic-range data with high peaks. We provide a mathematical approach to convert that column-centric scaling to our smooth envelope shape. This formalism allows us to use linear, root, and logarithmic scaling to find ideal dot sizes. Our method iteratively relaxes the dot layout for more correct and aesthetically pleasing results. To achieve this, we modified Lloyd's algorithm with additional constraints and heuristics. We evaluate the layouts of relaxed dot plots against a previously existing nonlinear variant and show that our algorithm produces less error regarding the underlying data while establishing the blue noise property that works against moiré effects. Further, we analyze the readability of our relaxed plots in three crowd-sourced experiments. The results indicate that our proposed technique surpasses traditional dot plots.

Counseling on Complementary Methods in the Treatment of Side Effects of Oncological Therapies: A Project of the Breast and Bowel Center Nahe at the Hospital Sankt Marienwoerth Bad Kreuznach.

BACKGROUND: Increasingly, patients with cancer are asking for additional, complementary therapy options for treating the side effects of oncological therapy. Thus, the members of the Breast and Bowel Center Nahe at the Sankt Marienwörth Hospital Bad Kreuznach decided to define the content of this type of counseling for patients before treatment. METHODS: In 2018, a team of internal oncologists, gynecological oncologists, radio-oncologists, nutritionists, psycho-oncologists, and study nurses met several times to define the content of counseling. To inform the team, an intensive literature review was conducted. RESULTS: Counseling content was determined for complementary treatment options for the most frequent side effects of oncological therapies. Counseling sessions were formulated as frontal lectures (slide presentations), given at regular intervals for patients and relatives. These lectures were highly appreciated by patients. CONCLUSION: These counseling sessions increased patient understanding of both useful complementary measures and harmful measures they should not use.

Operative Results and Perioperative Morbidity After Intensified Neoadjuvant Chemotherapy with FLOT for Gastroesophageal Adenocarcinoma Impact of Intensified Neoadjuvant Treatment.

BACKGROUND: Perioperative treatment is the standard of care in Western Europe for locally advanced gastric cancer (GC) and adenocarcinoma of the gastroesophageal junction (GEJ). Intensified neoadjuvant treatment within the NeoFLOT trial proved to be safe and effective. Yet, the influence of such intensification with 6 cycles of FLOT in the neoadjuvant setting has not been analyzed regarding its possible impact on perioperative results. MATERIALS AND METHODS: A total of 537 patients were enrolled in this study; of whom, 132 had followed a standard neoadjuvant protocol (CTx), 356 had not received any neoadjuvant treatment (NoCTx), and 49 patients had undergone an intensified chemotherapy within the NeoFLOT trial (IntCTx) with 6 cycles of FLOT (5-FU, leucovorin, oxaliplatin, docetaxel) every 2 weeks. RESULTS: Our results reveal no significant difference in perioperative morbidity or mortality with regard to the neoadjuvant treatment. Postoperative bleeding and hematoma occurred less frequently in the IntCTx group compared to the NoCTx and the CTx groups (2.0% vs. 5.33% vs. 5.1%). Postoperative lymph fistulas were slightly more frequent in the IntCTx group (4.1% vs. 0.3% vs. 1.6%). Patients treated within the NeoFLOT trial had a higher risk for blood transfusions (OR 5.5; 95%-KI, 2.49-12.19), whereas patients without neoadjuvant therapy had the longest ICU stay (mean 8.3 vs. CTx 4.5 vs. IntCTx 6.7 days). CONCLUSION: The results of the current study indicate that also an intensification of neoadjuvant chemotherapy with 6 preoperative cycles of FLOT does not significantly increase perioperative complications. Thus, prolonged neoadjuvant chemotherapy with FLOT is safe for patients with locally advanced GC or GEJ tumors.

2019 IEEE Scientific Visualization Contest Winner: Visual Analysis of Structure Formation in Cosmic Evolution.

Simulations of cosmic evolution are a means to explain the formation of the universe as we see it today. The resulting data of such simulations comprise numerous physical quantities, which turns their analysis into a complex task. Here, we analyze such high-dimensional and time-varying particle data using various visualization techniques from the fields of particle visualization, flow visualization, volume visualization, and information visualization. Our approach employs specialized filters to extract and highlight the development of so-called active galactic nuclei and filament structures formed by the particles. Additionally, we calculate X-ray emission of the evolving structures in a preprocessing step to complement visual analysis. Our approach is integrated into a single visual analytics framework to allow for analysis of star formation at interactive frame rates. Finally, we lay out the methodological aspects of our work that led to success at the 2019 IEEE SciVis Contest.

Predictive and prognostic value of magnesium serum level in FOLFIRI plus cetuximab or bevacizumab treated patients with stage IV colorectal cancer: results from the FIRE-3 (AIO KRK-0306) study.

Magnesium wasting is a frequent side effect of epidermal growth factor receptor (EGFR)-antibody treatment as magnesium-absorption mechanisms are dependent on EGFR signaling. EGFR-inhibition results in decreased renal reabsorption. There is evidence that hypomagnesemia during cetuximab treatment correlates with response. The prognostic role of hypomagnesemia during bevacizumab treatment has not been studied yet. Here, we evaluate the prognostic value of hypomagnesemia in patients with metastatic colorectal cancer treated with FOLFIRI plus cetuximab or bevacizumab as first-line therapy. A total of 391 of 752 patients of the firstline irinotecan study population had magnesium levels measured at baseline and for the first three cycles (6 weeks) of treatment. Of those, 240 had Rat Sarkoma wildtype tumors. Overall hypomagnesemia was more common in the cetuximab compared to the bevacizumab arm (80 vs. 43%, P < 0.005). During therapy, magnesium showed a time-dependent decrease to 80% of baseline in the cetuximab and to 89% in the bevacizumab arm. Whereas magnesium continued to decrease over time in the cetuximab-treated patients, it remained stable in the bevacizumab-treated. Overall response rate (ORR) was associated with higher magnesium at week 6 (20.9 vs. 79.1%, P = 0.041). Bevacizumab-treated patients with magnesium levels below the median value at week 6 had a significantly longer progression-free survival (PFS; 11.7 vs. 9.9 months, P = 0.034; hazard ratio 0.73) and a trend towards longer overall survival (OS) (29.6 vs. 23.2 months, P = 0.089; hazard ratio 0.77). Hypomagnesemia at predefined time points and magnesium nadir had no significant effect on ORR, OS and PFS in the cetuximab arm. Our data show different magnesium kinetics in patients with metastatic colorectal cancer treated with cetuximab or bevacizumab. For patients treated with cetuximab, hypomagnesemia did not have an impact on response and survival. Hypomagnesemia might have a prognostic value in bevacizumab treatment.

Metaphyseal Core Decompression of the Distal Radius for Early Lunate Necrosis.

Background: Metaphyseal core decompression of the distal radius (MCD) is clinically effective in early lunate necrosis without changing individual wrist mechanics. Its concept is based on the induction of physiologic mechanisms known as physiologic fracture healing response. However, this biological concept does not yet have its place in the historically developed mechanical concepts about Kienböck's disease and requires more detailed clarifications to understand when a change of individual wrist mechanics might be unnecessary. Methods: Thirteen consecutive cases, Lichtman stage I (n = 1) or II (n = 12), confirmed by conventional MRI, were treated by MCD. Time off work, changes in magnetic resonance imaging of the lunate, as well as clinical outcome using modified Mayo wrist score were evaluated at final follow-up. Results: Return to work was at six (1-10) weeks after surgery. MRI controls at short-term generally demonstrated stop of progression and signs of bone healing. Independently from ulna variance complete signal normalization was observed in six and a distinct, yet incomplete decrease of lunate bone marrow edema and zones of fat necrosis was confirmed in further six cases after a mean of 21 (13-51) weeks. One patient had radiographic controls only, stating normal healing at 56 months. After a mean follow-up of 37 (12-70) months the clinical outcomes were excellent in eleven and good in two cases (mean 95% in modified Mayo wrist score). Conclusions: In stage I and II lunate necrosis MCD stops disease progression, it improves clinical symptoms and induces normalization of lunate bone signal alterations in MRI. Findings suggest that stage I and II lunate necrosis can be effectively treated without alterations of individual wrist mechanics. Future studies are necessary to readjust common concepts regarding Kienböck's disease, especially focusing on conservative therapy.

Stippling of 2D Scalar Fields.

We propose a technique to represent two-dimensional data using stipples. While stippling is often regarded as an illustrative method, we argue that it is worth investigating its suitability for the visualization domain. For this purpose, we generalize the Linde-Buzo-Gray stippling algorithm for information visualization purposes to encode continuous and discrete 2D data. Our proposed modifications provide more control over the resulting distribution of stipples for encoding additional information into the representation, such as contours. We show different approaches to depict contours in stipple drawings based on locally adjusting the stipple distribution. Combining stipple-based gradients and contours allows for simultaneous assessment of the overall structure of the data while preserving important local details. We discuss the applicability of our technique using datasets from different domains and conduct observation-validating studies to assess the perception of stippled representations.

Comparable outcome after haploidentical and HLA-matched allogeneic stem cell transplantation for high-risk acute myeloid leukemia following sequential conditioning-a matched pair analysis.

In acute myeloid leukemia (AML), primary refractory or relapsed disease, secondary AML, and leukemia with unfavorable genetics are considered high-risk AML (hrAML), with allogeneic stem cell transplantation (SCT) representing the standard treatment. Sequential conditioning has been successfully used for SCT in hrAML in HLA-matched transplants, and found its way into HLA-haploidentical SCT (haplo-SCT) later on. Hence, sequential conditioning had become standard for all patients with hrAML in our two centers, regardless of donor type. Thereby, HLA-matched family or unrelated transplants were first/second choice, post-transplant cyclophosphamide (PTCY)-based haplo-SCT was chosen in patients missing matched donors or requiring urgent transplantation. To compare the outcome after HLA-matched and haplo-SCT for hrAML following sequential conditioning, we performed a retrospective, matched-pair comparison, using disease stage, genetic subgroups and age as matching criteria. Thirty-four well-matched pairs were identified. At SCT, patients (median age 54 years) were untreated (9%), had remission (13%), or active disease (78%). Three-year overall and leukemia-free survival (OS/LFS) of the entire cohort was 56 ± 7%/49 ± 7%, without significant differences between donor types (OS after HLA-matched/haplo-SCT 62 ± 10%/52 ± 9% (p = 0.21), LFS 53 ± 10%/46 ± 9% (p = 0.26)). Similarly, the cumulative incidence of relapse, non-relapse-mortality and chronic GvHD, as well as GvHD-free, relapse-free survival (GRFS), and chronic GvHD-free, relapse-free survival (cGRFS), were comparable. However, a higher incidence of acute GvHD ≥ II° was observed after HLA-matched SCT (15 ± 1% versus 50 ± 2%, p = 0.001). In conclusion, sequential conditioning SCT achieved remarkable results in hrAML, independently from donor type. PTCY-based haplo-SCT produced results that were comparable to HLA-matched SCT and can be used as an alternative option.

Sequential HLA-haploidentical transplantation utilizing post-transplantation cyclophosphamide for GvHD prophylaxis in high-risk and relapsed/refractory AML/MDS.

This study evaluates the role of sequential therapy in HLA-haploidentical transplantation (haplo-HSCT) of high-risk, relapsed/refractory AML/MDS. We analyzed the course of 33 adults with active disease at time of transplantation (AML n = 30; MDS n = 3; median age 58 years, range: 32-71). Sequential therapy consisted of cytoreductive chemotherapy (FLAMSA n = 21; clofarabine n = 12) applied shortly prior to reduced intensity conditioning for T-cell-replete haplo-HSCT using post-transplantation cyclophosphamide as GvHD prophylaxis. No graft rejection was observed. Complete remission at day +30 was achieved in 97% of patients. CI of acute GvHD grade II-IV and chronic GvHD was 24% (no grade IV) and 23%, respectively. NRM at 1 and 3 years was 15%, each. Severe regimen-related toxicities (grade III-IV) were observed in 58%, predominantly involving the gastrointestinal tract (diarrhea 48%, mucositis 15%, transient elevation of transaminases 18%). Probability of relapse at 1 and 3 years was 28% and 35%. At a median follow-up of 36 months, the estimated 1- and 3-year overall survival was 56% and 48%. Disease-free survival was 49% and 40%, respectively. At 3 years, GvHD and relapse-free survival (GRFS) was 24% while chronic GvHD and relapse-free survival (CRFS) was 29%. Thus, our results indicate that sequential haplo-HSCT is an effective salvage treatment providing high anti-leukemic activity, favorable tolerance, and acceptable toxicity in patients suffering from advanced AML/MDS.

Extracorporeal Membrane Oxygenation in Predominantly Leuco- and Thrombocytopenic Haematologic/Oncologic Patients with Acute Respiratory Distress Syndrome - a Single-Centre Experience.

AIMS: The acute respiratory distress syndrome (ARDS) is a frequent condition following pneumonia in immunocompromised cancer patients. Extracorporeal membrane oxygenation (ECMO) may serve as a rescue therapy in refractory ARDS but has still not been studied in predominantly leuco- and thrombocytopenic cancer patients. PATIENTS AND METHODS: In this monocentric, retrospective, observational study, we assessed all cancer patients treated with ECMO for ARDS between 2013 and 2017. RESULTS: 25 patients, 11 of whom underwent haematopoietic stem cell transplantation (SCT), were analysed. The main reason for ARDS was pneumonia in 72%. All patients were under invasive ventilation at ECMO. All but 9/3 patients suffered from leuco-/thrombocytopenia due to anti-cancer treatment or underlying disease. Overall, 17 patients (68%) died on ECMO, whereas 5 patients survived to hospital discharge (20%). All patients after recent allogeneic (allo-)SCT have died. 4 patients experienced severe bleeding events. CONCLUSIONS: Discouraging survival rates in patients treated after allo-SCT do not support the use of ECMO for ARDS in this patient subgroup. On the contrary, cancer patients in at least stable disease otherwise eligible for full-code intensive care unit management, even those with severe thrombocytopenia, may be potential candidates for ECMO in case of severe ARDS failing conventional measures.

Bubble Treemaps for Uncertainty Visualization.

We present a novel type of circular treemap, where we intentionally allocate extra space for additional visual variables. With this extended visual design space, we encode hierarchically structured data along with their uncertainties in a combined diagram. We introduce a hierarchical and force-based circle-packing algorithm to compute Bubble Treemaps, where each node is visualized using nested contour arcs. Bubble Treemaps do not require any color or shading, which offers additional design choices. We explore uncertainty visualization as an application of our treemaps using standard error and Monte Carlo-based statistical models. To this end, we discuss how uncertainty propagates within hierarchies. Furthermore, we show the effectiveness of our visualization using three different examples: the package structure of Flare, the S&P 500 index, and the US consumer expenditure survey.

Pattern and Dynamics of Distant Metastases in Metastatic Colorectal Cancer.

BACKGROUND: Few studies report the incidence of metastatic patterns in colorectal cancer. Furthermore, little is known about dynamic aspects of these metastases during the course of disease. METHODS: This retrospective cohort study involved 385 patients who received anti-tumor treatment at our institution (Department of Medical Oncology, University Hospital Grosshadern, Ludwig-Maximilians-University Munich, Germany) for metastatic colorectal adenocarcinoma between 2007 and 2014. We reviewed all available imaging results of these patients to document the presence and detailed localization of metastases. RESULTS: Most of the evaluated patients were initially diagnosed with metastases in the liver (70%), followed by the lungs (24%), distant lymph nodes (16%), and peritoneum (15%), besides rare anatomical sites (<5%). Colon and rectal cancer as well as synchronous and metachronous metastases differed with regard to the pattern of individual metastatic sites. The median time to first progressive disease (PD) with new metastases was 12.6 months. The time intervals between first and second as well as second and third PD with new metastases were comparable with 10.5 and 10.8 months, respectively. At initial diagnosis, the mean number of metastatic sites was 1.4 and increased to 2.6 at the third PD with new metastases. For patients with initially one metastatic site, the mean number increased to 2.2. CONCLUSION: The present analysis provides detailed information on the pattern and evolution of colorectal cancer metastases over time. Thus, it may establish the basis for prospective future research in this field.

Probabilistic Graph Layout for Uncertain Network Visualization.

We present a novel uncertain network visualization technique based on node-link diagrams. Nodes expand spatially in our probabilistic graph layout, depending on the underlying probability distributions of edges. The visualization is created by computing a two-dimensional graph embedding that combines samples from the probabilistic graph. A Monte Carlo process is used to decompose a probabilistic graph into its possible instances and to continue with our graph layout technique. Splatting and edge bundling are used to visualize point clouds and network topology. The results provide insights into probability distributions for the entire network-not only for individual nodes and edges. We validate our approach using three data sets that represent a wide range of network types: synthetic data, protein-protein interactions from the STRING database, and travel times extracted from Google Maps. Our approach reveals general limitations of the force-directed layout and allows the user to recognize that some nodes of the graph are at a specific position just by chance.

Establishment of triglyceride cut-off values to detect chylous ascites and pleural effusions.

OBJECTIVES: Lipoprotein electrophoresis is the gold standard for the detection of chylous ascites and pleural effusions. It is, however, not suitable as a front-line test and not widely available. Most clinicians must rely solely on the quantitative determination of lipids. The aim of this work was to establish lipid cut-off values for the presence of chylomicrons in pleural and peritoneal fluid. DESIGN AND METHODS: Triglyceride and cholesterol levels from 113 peritoneal and 154 pleural fluid samples investigated for chylomicrons via lipoprotein electrophoresis were considered. Receiver operating characteristic analyses were performed and cut-off levels determined. RESULTS: 54 peritoneal and 59 pleural fluid samples were positive for chylomicrons. In peritoneal fluid, triglycerides and triglycerides/cholesterol ratio exhibited areas under the curve (AUC) not significantly different from each other, but significantly larger than cholesterol alone. The AUC for triglycerides in pleural fluid was significantly larger than the AUCs for cholesterol and the triglycerides/cholesterol ratio. Triglyceride cut-offs with maximum Youden-Index, sensitivity >95%, and specificity >95% were calculated to be 187, 148, and 246mg/dl (2.13, 1.69, and 2.80mmol/l) for peritoneal fluid, and 240, 94, and 240mg/dl (2.74, 1.07, and 2.74mmol/l) for pleural fluid. CONCLUSIONS: Triglyceride levels are the best parameter to detect chylous body fluids when lipoprotein electrophoresis is not available. Single-point triglyceride cut-offs of 187 and 240mg/dl (2.13 and 2.74mmol/l) or alternatively equivocal ranges of 148-246 and 94-240mg/dl (1.69-2.80 and 1.07-2.74mmol/l) were established for peritoneal and pleural fluid, respectively.

Occurrence, risk factors and outcome of adenovirus infection in adult recipients of allogeneic hematopoietic stem cell transplantation.

BACKGROUND: Adenovirus (ADV) infections can have a high mortality in immunocompromised patients and are difficult to treat. OBJECTIVES AND STUDY DESIGN: We retrospectively analyzed occurrence and risk factors of ADV infection in 399 adults with hematological disorders undergoing hematopoietic stem cell transplantation (allo-HSCT), focusing on alternative donor transplantation (ADT) and disseminated disease. RESULTS: ADV infection occurred in 42 patients (10.5%). Disease was localized in 18 and disseminated in 6 patients. ADV infection was observed in 15% after ADT, performed in 29% of all recipients, and was less frequent (6%) in T-cell-replete (TCR) haploidentical transplantation using post-transplantation cyclophosphamide (PTCY) than in other ADT protocols. Lower age, the use of alternative donor grafts and acute graft-versus-host disease (GvHD)≥grade II were risk factors for ADV infection. After failure of standard antiviral treatment, three patients with disseminated ADV disease received one dose of ADV-specific T cells, resulting in virological response in 2/3 patients, clearance of ADV viremia in 2/2 patients, and survival of 1/3 patients; both patients with pneumonia died. CONCLUSIONS: ADV infection was of moderate occurrence in our adult recipients of allo-HSCT despite a high proportion of potential high-risk patients receiving ADT. TCR strategies using PTCY might limit ADV complications in haploidentical transplantation. Despite feasible adoptive therapy strategies, outcome of disseminated disease remains dismal.