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Background Scavenger receptor CD163 is exclusively expressed on monocytes/macrophages and is widely used as a marker for alternatively activated macrophages. However, the role of CD163 is not yet clear. Objectives We sought to examine the function of CD163 in steady-state as well as in sterile and infectious inflammation. Methods Expression of CD163 was analyzed under normal and inflammatory conditions in mice. Functional relevance of CD163 was investigated in models of inflammation in wild-type and CD163−/− mice. Results We describe a subpopulation of bone marrow–resident macrophages (BMRMs) characterized by a high expression of CD163 and functionally distinct from classical bone marrow–derived macrophages. Development of CD163+ BMRMs is strictly dependent on IFN regulatory factor-8. CD163+ BMRMs show a specific transcriptome and cytokine secretion pattern demonstrating a specific immunomodulatory profile of these cells. Accordingly, CD163−/− mice show a stronger inflammation in allergic contact dermatitis, indicating a regulatory role of CD163. However, CD163−/− mice are highly susceptible to S aureus infections, demonstrating the relevance of CD163 for antimicrobial defense as well. Conclusions Our data indicate that anti-inflammatory and immunosuppressive mechanisms are not necessarily associated with a decreased antimicrobial activity. In contrast, our data define a novel macrophage population that controls overwhelming inflammation on one hand but is also necessary for an effective control of infections on the other hand.

Background With regard to quality of life and organ shortage, follow-up after liver transplantation (LT) should consider risk factors for allograft failure in order to avoid the need for re-LT and to improve the long-term outcome of recipients. Therefore, the aim of this study was to explore potential risk factors for allograft failure after LT. Material and methods A total of 489 consecutive LT recipients who received follow-up care at the University Hospital of Muenster were included in this study. Database research was performed, and patient data were retrospectively reviewed. Risk factors related to donor and recipient characteristics potentially leading to allograft failure were statistically investigated using binary logistic regression analysis. Graft failure was determined as graft cirrhosis, need for re-LT because of graft dysfunction, and/or allograft-associated death. Results The mean age of recipients at the time of LT was 50.3 ± 12.4 years, and 64.0 % were male. The mean age of donors was 48.7 ± 15.5 years. Multivariable statistical analysis revealed male recipient gender (p = 0.04), hepatitis C virus infection (HCV) (p = 0.014), hepatocellular carcinoma (HCC) (p = 0.03), biliary complications after LT (p Conclusion Male recipients, patients who received LT for HCV or HCC, those with pretransplant diabetes mellitus, and LT recipients with biliary complications are at high risk for allograft failure and thus should be monitored closely.

Supplemental Digital Content is available in the text., Objectives: Acute-on-chronic liver failure is associated with numerous consecutive organ failures and a high short-term mortality rate. Molecular adsorbent recirculating system therapy has demonstrated beneficial effects on the distinct symptoms, but the associated mortality data remain controversial. Design: Retrospective analysis of acute-on-chronic liver failure patients receiving either standard medical treatment or standard medical treatment and molecular adsorbent recirculating system. Secondary analysis of data from the prospective randomized Recompensation of Exacerbated Liver Insufficiency with Hyperbilirubinemia and/or Encephalopathy and/or Renal Failure trial by applying the recently introduced Chronic Liver Failure-criteria. Setting: Medical Departments of University Hospital Muenster (Germany). Patients: This analysis was conducted in two parts. First, 101 patients with acute-on-chronic liver failure grades 1–3 and Chronic Liver Failure-C-Organ Failure liver subscore equals to 3 but stable pulmonary function were identified and received either standard medical treatment (standard medical treatment, n = 54) or standard medical treatment and molecular adsorbent recirculating system (n = 47) at the University Hospital Muenster. Second, the results of this retrospective analysis were tested against the Recompensation of Exacerbated Liver Insufficiency with Hyperbilirubinemia and/or Encephalopathy and/or Renal Failure trial. Interventions: Standard medical treatment and molecular adsorbent recirculating system. Measurements and Main Results: Additionally to improved laboratory variables (bilirubin and creatinine), the short-term mortality (up to day 14) of the molecular adsorbent recirculating system group was significantly reduced compared with standard medical treatment. A reduced 14-day mortality rate was observed in the molecular adsorbent recirculating system group (9.5% vs 50.0% with standard medical treatment; p = 0.004), especially in patients with multiple organ failure (acute-on-chronic liver failure grade 2–3). Concerning the affected organ system, this effect of molecular adsorbent recirculating system on mortality was particularly evident among patients with increased kidney, brain, or coagulation Chronic Liver Failure-C-Organ Failure subscores. Subsequent reanalysis of the Recompensation of Exacerbated Liver Insufficiency with Hyperbilirubinemia and/or Encephalopathy and/or Renal Failure dataset with adoption of the Chronic Liver Failure-classification resulted in similar findings. Conclusions: Molecular adsorbent recirculating system treatment was associated with an improved short-term survival of patients with acute-on-chronic liver failure and multiple organ failure. Among these high-risk patients, molecular adsorbent recirculating system treatment might bridge to liver recovery or liver transplantation.

Als extrakorporale Leberunterstutzungstherapie werden die zellfreien – artifiziellen Verfahren (artificial liver support, ALS) von den zellbasierten – bioartifiziellen Verfahren (bioartificial liver support, BLS) unterschieden. Die artifiziellen Verfahren, verbessern durch die gleichzeitige Entfernung von proteingebundenen und wasserloslichen Substanzen biochemische Parameter des Leberversagens. Hierbei gehort die MARS-Therapie zu dem am besten untersuchten Verfahren, wobei ein Effekt bzgl. der Symptomkontrolle der hepatischen Enzephalopathie (HE), dem hepatorenalen Syndrom (HRS) oder der Hyperbilirubinamie nachgewiesen werden konnte. Ein genereller Uberlebensvorteil jedweder Leberdialyse beim Leberversagen lasst sich jedoch nicht bzw. nur in Metaanalysen oder fur Subgruppen zeigen. Es existieren keine prospektiv randomisierten Studien zur Therapie des Leberversagens durch Intoxikationen. Mehrere Fallserien berichten jedoch von positiven Therapieeffekten unter Verwendung des MARS-Systems, insbesondere bei Knollenblatterpilzvergiftungen oder Paracetamolintoxikationen. Beim akuten Leberversagen (ALF) konnten Studien unter Verwendung der BLS keinen Uberlebensvorteil zeigen. Unter Verwendung von ALS-Systemen konnte in Patientensubgruppen nach mehreren konsekutiven MARS-Therapien ein positiver Effekt auf die Mortalitat erreicht werden. Die bislang einzige prospektiv, randomisierte Studie mit signifikantem Uberlebensvorteil verwendete grosvolumige Plasmapherese als Therapieverfahren. Offenbar spielen hier immunmodulatorische und hamodynamische Effekte der Therapie eine entscheidende Rolle. Bei Patienten mit akut-auf-chronischem Leberversagen (acute on chronic liver failure, ACLF) und Hyperbilirubinamie ohne weiteres Organversagen (singulare hepatische Dysfunktion) hat ein BLS-System prognostisch gunstige Effekte gezeigt. Sobald jedoch auch andere extrahepatische Organsysteme betroffen sind und ein fortschreitender Ubergang ins Multiorganversagen vorliegt, konnte mit dem MARS- bzw. Prometheus-Systems ein Uberlebensvorteil erreicht werden. Entscheidend fur einen Therapieerfolg ist die genaue Indikationsstellung des jeweiligen Leberdialyseverfahrens bei diesem sehr heterogenen Krankheitsbild. Zukunftige Studien sind notig, um genauere Patientenselektionskriterien bzgl. des jeweiligen Leberunterstutzungsverfahrens zu definieren.

Patients undergoing intensive chemotherapy for acute myeloid leukemia are at high risk for bacterial infections during therapy-related neutropenia. However, the use of specific antibiotic regimens for prophylaxis in afebrile neutropenic acute myeloid leukemia patients is controversial. We report a retrospective evaluation of 172 acute myeloid leukemia patients who received 322 courses of myelosuppressive chemotherapy and had an expected duration of neutropenia of more than seven days. The patients were allocated to antibiotic prophylaxis groups and treated with colistin or ciprofloxacin through 2 different hematologic services at our hospital, as available. The infection rate was reduced from 88.6% to 74.2% through antibiotic prophylaxis (vs. without prophylaxis; P=0.04). A comparison of both antibiotic drugs revealed a trend towards fewer infections associated with ciprofloxacin prophylaxis (69.2% vs. 79.5% in the colistin group; P=0.07), as determined by univariate analysis. This result was confirmed through multivariate analysis (OR: 0.475, 95%CI: 0.236–0.958; P=0.041). The prophylactic agents did not differ with regard to the microbiological findings (P=0.6, not significant). Of note, the use of ciprofloxacin was significantly associated with an increased rate of infections with pathogens that are resistant to the antibiotic used for prophylaxis (79.5% vs. 9.5% in the colistin group; P

Allogeneic stem cell transplantation (SCT) remains the best curative option for patients with refractory AML or with high-risk myelodysplastic syndrome (MDS). For decades, age alone had been widely used as the primary criterion to assess eligibility for allogeneic SCT; however, prospective studies to evaluate allogeneic SCT in elderly patients are still limited. A total of 187 patients (median age of 64 years, range 60-77 years) with AML (87%) or MDS (13%) transplanted between 1999 and 2014 were included in this retrospective analysis. Relapse-free survival (RFS) and overall survival (OS) at 3 years were 32% (95% confidence interval (CI): 25-39%) and 35% (95%CI: 27-42%), respectively. Overall survival was 49% (95%CI: 35-64%) in AML patients who were transplanted in first complete remission (CR1), but even patients with active disease did benefit from transplantation, showing an OS at 3 years of 30% (95%CI: 20-40%). Multivariate analysis revealed disease- and patient-specific risk indices as independent prognostic factors for OS and non-relapse mortality (NRM). In conclusion, our monocenter results indicate that patients should not be generally withheld from allogeneic SCT because of age or disease status only. Specific risk models incorporating disease status and disease-specific risk factors at the time of transplantation as well as existing comorbidities are helpful tools to assess transplantation-associated risk factors of elderly patients.

We evaluated pazopanib (800 mg orally QD) in patients not eligible for intensive treatment with relapsed/refractory AML or at initial diagnosis. Patients receiving pazopanib for > 14 days were analyzed for safety, tolerability, and efficacy. Co-primary endpoints were cumulative response rate and reduction of bone marrow microvessel density. Twenty patients (median age 76 years, range 52–86) were treated. Fifteen had relapsed/refractory and five had newly diagnosed AML. Median ECOG performance status was 1 (range 1–3). Four patients had adverse, 15 intermediate, and 1 patient favorable cytogenetic/molecular risk (ELN 2010 criteria). The safety profile of pazopanib was as reported. The most common adverse events of any grade were gastrointestinal. Two patients achieved PR (blast reduction > 50%), 14 stable disease (SD), and 4 progressive disease. Median PFS was 65 days (95% CI 29–105). After the end of the study, 1 CRi and 1 CRp occurred on demethylating agents, and 1 CR upon alloSCT. In these patients, SD and improved general condition on pazopanib allowed therapy escalation. Median OS for the overall study population was 191 days (95% CI 87–435) and 1-year survival was 35%. There was no significant change in microvessel density. Clinical trial information: NCT01361334.

With regard to quality of life and organ shortage, follow-up after liver transplantation (LT) should consider risk factors for allograft failure in order to avoid the need for re-LT and to improve the long-term outcome of recipients. Therefore, the aim of this study was to explore potential risk factors for allograft failure after LT.A total of 489 consecutive LT recipients who received follow-up care at the University Hospital of Muenster were included in this study. Database research was performed, and patient data were retrospectively reviewed. Risk factors related to donor and recipient characteristics potentially leading to allograft failure were statistically investigated using binary logistic regression analysis. Graft failure was determined as graft cirrhosis, need for re-LT because of graft dysfunction, and/or allograft-associated death.The mean age of recipients at the time of LT was 50.3 ± 12.4 years, and 64.0 % were male. The mean age of donors was 48.7 ± 15.5 years. Multivariable statistical analysis revealed male recipient gender (p = 0.04), hepatitis C virus infection (HCV) (p = 0.014), hepatocellular carcinoma (HCC) (p = 0.03), biliary complications after LT (p 0.001), pretransplant diabetes mellitus (p = 0.03), and/or marked fibrosis in the initial protocol biopsy during follow-up (p = 0.001) to be recipient-related significant and independent risk factors for allograft failure following LT.Male recipients, patients who received LT for HCV or HCC, those with pretransplant diabetes mellitus, and LT recipients with biliary complications are at high risk for allograft failure and thus should be monitored closely.Im Hinblick auf die Lebensqualität und den herrschenden Organmangel sollte die Nachsorge nach einer Lebertransplantation (LT) Risikofaktoren für eine Transplantatdysfunktion berücksichtigen, um sowohl die Langzeitergebnisse zu verbessern als auch Retransplantationen zu vermeiden. Ziel dieser Studie war es daher Risikofaktoren für ein Organversagen nach einer LT zu evaluieren.489 lebertransplantierte Patienten wurden konsekutiv in diese retrospektive Studie eingeschlossen. Es wurde eine Datenbankrecherche durchgeführt. Mittels einer binären Regressionsanalyse wurden potentielle Risikofaktoren eines Transplantatversagens nach einer LT ermittelt. Als Transplantatversagen wurden eine Transplantatzirrhose, die Notwendigkeit einer Re-LT und der transplantatassoziierte Tod definiert.Das mittlere LT-Empfängeralter lag bei 50,3 ± 12,4 Jahren. 64 % der Empfänger waren männlich. Das Spenderalter lag bei 48,7 ± 15,5 Jahren. Die statistische Analyse ergab folgende unabhängige Risikofaktoren für ein Transplantatversagen: männliches Empfängergeschlecht (p = 0,04), Hepatitis-C-Virus-Infektion (HCV) (p = 0,014) und hepatozelluläres Karzinom (HCC) (p = 0,03) als Grunderkrankung, Prätransplantationsdiabetes (p = 0,03) sowie biliäre Komplikationen (p 0,001) und/oder deutliche Fibrose in der Protokoll-Biopsie während der Nachsorgezeit (p = 0,001).Männliche Empfänger, Patienten mit HCV bzw. HCC als Grunderkrankungen, solche mit Prätransplantationsdiabetes sowie LT-Empfänger mit biliären Komplikationen haben ein erhöhtes Risiko für ein Transplantatversagen und sollten daher speziell hinsichtlich dieser Risikofaktoren nachgesorgt werden.

Extracorporeal liver support can be classified into cell-free, artificial methods (artificial liver support, ALS) and cell-based bioartificial methods (bioartificial liver support, BLS). ALS improves biochemical parameters of liver failure by the simultaneous removal of protein-bound and water-soluble substances. Here, the MARS therapy belongs to the most studied methods with a proved beneficial effect on hepatic encephalopathy (HE), hepatorenal syndrome (HRS) or hyperbilirubinemia. However, a general survival advantage of any liver support for liver failure has not been shown yet and is restricted to meta-analyses or patient subgroups. There are no prospective randomized studies on the treatment of liver failure by intoxication. However, several case series report positive treatment effects using the MARS system, particularly in mushroom poisoning or acetaminophen intoxication. In acute liver failure (ALF) studies, the usage of BLS showed no survival advantage. Using ALS systems, a positive effect on mortality could be demonstrated in patient subgroups after several consecutive MARS therapies. The first randomized controlled trial demonstrating a survival benefit used large-volume plasmapheresis. Apparently, immunomodulatory and hemodynamic effects of the treatment play a crucial role in this context. In patients with acute-on-chronic liver failure (ACLF) accompanied by hyperbilirubinemia without any further organ failure (singular hepatic dysfunction), prognostic favorable effects by using a BLS system have been shown. However, once other extrahepatic organ systems are affected, indicating a progressive transition to multi-organ failure, a survival advantage could be achieved with the MARS and Prometheus system. Decisive for a successful therapy is the exact indication of the respective liver dialysis procedure for this very heterogeneous disease. Future studies are needed to define more accurate patient selection criteria for each liver support.

Background The primary therapeutic goals in the treatment of liver injury are to support liver regeneration or bridge the gap to liver transplantation (LT). Molecular adsorbent recirculating system (MARS) therapy has shown beneficial effects for specific symptoms of liver failure; however, general survival advantages have not yet been demonstrated. Aim We studied the effects of MARS therapy compared to standard medical treatment (SMT) in two patient cohorts: in patients with an acute liver injury and in those with graft dysfunction (GD). Methods We report on our experience over a 6.5-year period with 73 patients treated with SMT or with SMT and MARS (MARS group). In total, 53 patients suffered from acute liver injury in their native liver without a preexisting liver disease (SMT: n = 31, MARS: n = 22), and 20 patients showed a severe GD after LT (SMT: n = 10, MARS: n = 10). Results The entire cohort was predominantly characterized by hemodynamically and respiratorily stable patients with a low hepatic encephalopathy (HE) grade and a model of end-stage liver disease (MELD) score of 20.57 (MARS) or 22.51 (SMT, p = 0.555). Within the MARS group, the median number of extracorporeal therapy sessions was four (range = 3–5 sessions). Independent of the underlying etiology, MARS improved the patients’ bilirubin values in the short term compared to SMT alone. In patients with acute liver injury, this response was sustained even after the end of MARS therapy. By contrast, the majority of patients with GD and an initial response to MARS therapy experienced worsened hyperbilirubinemia. No differences in 28-day mortality were observed with respect to acute liver injury (MARS 5.3% (95% CI: 0–15.3); SMT 3.3% (95% CI: 0–9.8), p = 0.754) or GD (MARS 20.0% (95% CI: 0–44.7), SMT 11.1% (95% CI: 0–31.7), p = 0.478). Conclusions Although it did not improve 28-day mortality, MARS therapy improved the short-term response in patients with acute liver injury as well as in those with GD. In cases of acute hepatic injury, the use of MARS therapy resulted in the sustained stabilization of liver function and improved liver regeneration. A short-term response to MARS may predict the future course of the disease.

BACKGROUND:High-cut-off hemodialysis (HCO-HD) can effectively reduce high concentrations of circulating serum free light chains (sFLC) in patients with dialysis-dependent acute kidney injury (AKI) due to multiple myeloma (MM). Therefore, the aim of this study was to analyze renal recovery in a retrospective single-center cohort of dialysis-dependent MM patients treated with either conventional HD (conv. HD) or HCO-HD. METHODS AND RESULTS:The final cohort consisted of 59 patients treated with HCO-HD (n = 42) or conv. HD (n = 17). A sustained sFLC response was detected in a significantly higher proportion of HCO-HD patients (83.3%) compared with conv. HD patients (29.4%; p = 0.007). The median duration of sFLC required to reach values

There have been several attempts to improve treatment and outcome of patients with primary mediastinal B-cell lymphoma (PMBL) and Burkitt's lymphoma (BL). In recent years, chemotherapy dose intensification and the addition of rituximab have led to a remarkable progress and have developed into integral parts of treatment for both entities of lymphoma [1–4]. Here, we report our monocenter results of a high-dose methotrexate based alternating regimen with rituximab (B-ALL/NHL 2002 protocol) in 15 patients with PMBL and 28 patients with sporadic BL. Since the early 1980s, protocols of GMALL have been continuously adapted and in the meantime they have become reference treatment for BL and B-ALL in Germany. The latest changes comprised the additional use of rituximab, standardized G-CSF support,implementation of high-dose cytarabine, intrathecal triple therapy,and age-adjusted stratification. Furthermore, we additionally amended supportive care with palifermin as it reduced severity and prevalence of mucositis [5].

A few recent studies suggested that anaemia has a marked impact on the survival of patients with coronary heart disease (CHD). However, all of these analyses did not take into consideration that chronic kidney disease (CKD) plays an important role in erythropoiesis and anaemia. Therefore, we assessed in this study whether anaemia is an independent predictor of mortality or if its impact was confounded by CKD, which is known to have itself a marked impact on outcomes of patients with CHD.In a retrospective cohort study, we analysed 709 patients with symptomatic and significant CHD who underwent percutaneous coronary interventions. Patients were classified as anaemic using the WHO definition; renal function was classified by the estimated glomerular filtration rate (eGFR).In comparison with non-anaemic patients, anaemic patients had a significantly higher in-hospital mortality (4.9 vs 0.5%, P0.001). Moreover, 1-year mortality rates of anaemic patients were significantly higher regardless of whether they had a normal eGFR (22 vs 2.8%, P=0.029), an eGFR of 60-89 ml/min (14 vs 4.2%, P0.001), an eGFR of 30-59 ml/min (21 vs 3.7%, P0.001) or an eGFR30 ml/min (26 vs 0%, NS). When cumulative mortality was analysed by haemoglobin concentrations in steps of 1 g/dl from11.0 g/dl to16.9 g/dl, 1-year mortality rates were 28, 18, 15, 5.5, 3.8, 5.7, 1.5 and 0%, respectively (P0.001, log rank). Even after adjustment for comorbidities by multivariable Cox regression models, haemoglobin remained a significant predictor of long-term mortality (hazard rate ratio 0.77, 95% confidence interval (CI): 0.62-0.82, P0.001) while eGFR was not (hazard rate ratio 1.0, 95% CI: 0.99-1.01).Anaemia was found to be a strong and independent predictor of acute and long-term mortality in patients with symptomatic CHD, regardless of the presence of CKD.

Papillary renal cell carcinoma (PRCC) is a rare malignant tumor entity compared to common clear cell renal carcinoma. In the present study, we report a patient who was diagnosed with PRCC twice and successfully treated each time following renal transplantation. The first PRCC was located in the left native kidney two years following transplantation, and the second PRCC was diagnosed in the allograft 13 years following transplantation. The two tumors were completely removed by surgery in stage I of the disease with sufficient conservation of the allograft function. Notably, the tumors had a different origin as indicated by the microsatellite analysis, which reflects the exceptional course of the case. Risk factors for PRCC were identified in our patient. We concluded that high-risk candidates for malignancies in renal transplant recipients should receive shorter ultrasonic screening intervals, which may facilitate early tumor detection and improve outcome rates.

AIM To evaluate cholangioscopy in addition to endoscopic retrograde cholangiopancreatography (ERCP) for management of biliary complications after liver transplantation (LT). METHODS Twenty-six LT recipients with duct-to-duct biliary reconstruction who underwent ERCP for suspected biliary complications between April and December 2016 at the university hospital of Muenster were consecutively enrolled in this observational study. After evaluating bile ducts using fluoroscopy, cholangioscopy using a modern digital single-operator cholangioscopy system (SpyGlass DS™) was performed during the same procedure with patients under conscious sedation. All patients received peri-interventional antibiotic prophylaxis and bile was collected during the intervention for microbial analysis and for antibiotic susceptibility testing. RESULTS Thirty-three biliary complications were found in a total of 22 patients, whereas four patients showed normal bile ducts. Anastomotic strictures were evident in 14 (53.8%) patients, non-anastomotic strictures in seven (26.9%), biliary cast in three (11.5%), and stones in six (23.1%). A benefit of cholangioscopy was seen in 12 (46.2%) patients. In four of them, cholangioscopy was crucial for selective guidewire placement prior to planned intervention. In six patients, biliary cast and/or stones failed to be diagnosed by ERCP and were only detectable through cholangioscopy. In one case, a bile duct ulcer due to fungal infection was diagnosed by cholangioscopy. In another case, signs of bile duct inflammation caused by acute cholangitis were evident. One patient developed post-interventional cholangitis. No further procedure-related complications occurred. Thirty-seven isolates were found in bile. Sixteen of these were gram-positive (43.2%), 12 (32.4%) were gram-negative bacteria, and Candida species accounted for 24.3% of all isolated microorganisms. Interestingly, only 48.6% of specimens were sensitive to prophylactic antibiotics. CONCLUSION Single-operator cholangioscopy can provide important diagnostic information, helping endoscopists to plan and perform interventional procedures in LT-related biliary complications.

The tumor-directed delivery of therapeutics using monoclonal antibodies specific to a tumor-associated antigen promises to accumulate large doses of the delivered payload at the tumor site while sparing healthy organs. The antibody-based delivery of interleukin-2 (IL-2) to extracellular targets expressed in the easily accessible tumor vasculature has shown promising results in animal models of solid tumors and hematological malignancies. In xenograft and immunocompetent murine models of acute myeloid leukemia (AML), IL-2-based vascular targeting antibody fusions have recently demonstrated potent anti-leukemic activity, especially when used in combination with cytarabine. Here, we report our experiences in four patients with relapsed AML after allogeneic hematopoietic stem cell transplantation (allo-HSCT), who were treated with the immunocytokine F16-IL2, consisting of a human monoclonal antibody specific to spliced large isoforms of tenascin-C fused to human IL-2, in combination with very low dose cytarabine (5 mg subcutaneously twice daily for 10 days). Clinical evidence of anti-leukemia efficacy was shown in all patients. One patient with rapidly progressing disseminated extramedullary AML lesions achieved a complete metabolic response in PET/CT, which lasted three months. Two out of three patients with bone marrow relapse achieved a blast reduction with transient molecular negativity (NPM1). One of the two enjoyed a short complete remission before AML relapse occurred two months after the first infusion of F16-IL2. The other patient did not regenerate neutrophil and thrombocyte counts and showed progressive disease after completion of the first cycle. In line with a site-directed delivery of the cytokine, F16-IL2 led to an extensive infiltration of immune effector cells (natural killer cells, CD8+ T cells, γδ T cells) in the bone marrow. Grade 2 fevers were the only non-hematological side effects in two patients. Grade 3 cytokine-release syndrome developed in the other two patients, required hospitalization, but was manageable in both cases with systemic glucocorticoids. No non-hematological grade 4 toxicities were observed. The concept of specifically targeting IL-2 to the leukemia-associated stroma using armed antibodies deserves further evaluation in clinical trials, especially in patients who relapse after allo-HSCT. Disclosures Off Label Use: In this report, the antibody-cytokine fusion protein F16-IL2 has been used in a compassionate use setting in individual patients presenting with AML relapse after allogeneic stem cell transplantation. F16-IL2 is currently being evaluated in phase I/II studies in patients with solid cancer.. Neri:Philogen SpA: Employment, Equity Ownership.

High-dose chemotherapy (HDT) followed by autologous stem cell transplantation (ASCT) is considered standard in the treatment of patients with relapsed or refractory aggressive peripheral T cell lymphoma (PTCL). However, the optimal salvage regimen before ASCT has not yet been established. We retrospectively analyzed 31 patients with relapsed or refractory aggressive PTCL after anthracycline-based first-line chemotherapy who received either DexaBEAM (dexamethasone, carmustine, etoposide, cytarabine, and melphalan; n = 16) or ICE (ifosfamide, carboplatin, and etoposide; n = 15) regimen as first salvage chemotherapy followed by HDT/ASCT. The overall response rate (OR) was significantly higher for patients treated with DexaBEAM (69 %; 95 % confidence interval 46.0–91.5 %) as compared to the ICE group (20 %; 95 % confidence interval −0.2–40.2 %; P = 0.01), with higher complete response (CR; 38 %; 95 % confidence interval 13.8–61.2 %; vs. 7 %; 95 % confidence interval −6.0–19.6 %) as well as partial response (PR; 31 vs. 13 %) rate. Changing regimen due to failure of first salvage therapy, 12 patients initially receiving ICE still achieved an OR of 58 % (33 % CR, 25 % PR) with DexaBEAM as second salvage therapy, whereas in three patients receiving ICE after DexaBEAM failure, only one achieved an OR (1 PR). Median progression-free survival was significantly higher in the DexaBEAM group (6.4 vs. 2 months; P = 0.01). Major adverse event in both groups was myelosuppression with higher but tolerable treatment-related toxicity for patients in the DexaBEAM group. For all patients proceeding to HDT/ASCT, a 3-year overall survival was 50 %. Together, considering the limitations of the retrospective design of the evaluation and the small sample size, our data suggest that DexaBEAM salvage chemotherapy is superior to ICE for patients with relapsed or refractory aggressive PTCL for remission induction prior to autologous transplantation, with higher but manageable treatment-related toxicity.

During recent years, numerous clinical and procedural risk factors for adverse outcomes after percutaneous coronary interventions (PCI) have been identified. Due to the high economic pressure in many national health care systems, it is of some interest whether these predictors of clinical risks represent also the main cost drivers. Data of 770 patients undergoing PCI were retrospectively analyzed. Risk factors for PCI as well as angiographic classifications were adopted from the ACC/AHA Guidelines. In-hospital costs for each patient were obtained from thoroughly performed calculations for the national Diagnosis Related Groups database in Germany. Creatinine >2 mg/dl (192% of average costs, P

Allogeneic SCT is the most potent post-remission therapy for AML patients, particularly in patients aged >40-45 years, and the only curative option for patients with refractory AML or with high-risk MDS. Although median age at diagnosis is above 65 years for both entities, for patients aged 60 years or older, studies evaluating allogeneic SCT as post-remission therapy or as salvage therapy are limited. Dose adapted / reduced conditioning for patients in remission and sequential conditioning (intensive chemotherapy followed by dose adapted conditioning), for patients with active leukemia / high-risk disease, together with improvement in supportive care, have shown improved outcome results for SCT in younger and older patients. Aiming to predict treatment outcomes of patients undergoing allogeneic SCT, various transplant specific risk models have been introduced in the past. Assuming that these risk models might be of value especially in older patients, we performed a retrospective single center analysis of transplanted patients, incorporating the Hematopoietic Cell Transplantation-Specific Comorbidity Index (HCT-CI), the European Group for Blood and Marrow Transplantation (EBMT) Score and the Disease Risk Index (DRI). Between 1999 and 2014, 187 patients (pts) with AML (87%) or MDS (13%) aged ≥60 years (median age of 64 years, range 60 - 77 years) received an allogeneic SCT at our institution, either from a HLA-identical related (50 pts.), HLA-matched unrelated (103 pts.), or an HLA-mismatched donor (34 pts). Median follow-up of surviving patients was 36 months (range 1 to 173 months). All patients with AML received a cytarabine-based standard induction therapy. Conditioning prior to transplant consisted of dose reduced / dose adapted therapy (TBI-, busulfan- or treosulfan-based) or sequential conditioning (for patients with high risk or refractory disease). Thirty-nine of the 47 AML patients transplanted in first complete remission (CR1) had a high-risk AML, defined by an adverse cytogenetic risk profile (16 pts), persisting AML after first induction therapy (12 pts), a secondary AML (6 pts.), or persisting / increasing minimal residual disease (5 pts). MDS patients had mainly an advanced disease with blast count 10-19% (19/24 pts). For all patients, an overall survival (OS) at 3 years of 35% (95% CI: 27-42%) was observed. Cumulative incidences of NRM and relapse at one year were 37% and 22%, respectively. Patients transplanted in CR1 showed a 3-year OS of 49%, whereas patients transplanted in subsequent remission, with active AML, or high-risk MDS had a 3-year OS of 26%, 28% and 31%, respectively. Univariate analysis of the whole group showed that advanced and/or active disease (advanced/active AML/MDS vs. AML CR1, p = .04), high DRI (high/very high vs. low/intermediate, p = .06), and poor Eastern Cooperative Oncology Group Score (ECOG; ≥2 vs. 0 or 1, p=.0001), were associated with an inferior OS. Patient age had no impact on outcome parameters. In a multivariate analysis of disease / transplant related risk factors (status pre transplant, EBMT-score, HCT-CI and DRI) only disease status pre transplant was an independent prognostic factor for OS (active / advanced disease vs. CR1, hazard ratio 1.55; 95% CI 1.01-2.38). These results indicate that patient's age ≥60 years in general is no limiting factor for an allogeneic transplant, even if refractory to conventional treatment. Pre-transplant selection of patients eligible for intensive treatment was most likely one relevant bias in our analysis, limiting the determination of the impact of preexisting comorbidities on treatment outcomes. Given the prognostic impact of the disease status at transplant, the improvement of transplant results in elderly patients, and the dismal prognosis of older patients with myeloid neoplasms receiving conventional treatment, the impact of allogeneic SCT, especially in early disease stages / CR1 of patients with MDS / AML eligible for intensive treatment has to be further studied in prospective trials. Disclosures No relevant conflicts of interest to declare.

8548 Background: High-dose chemotherapy (HDT) followed by autologous stem-cell transplantation (ASCT) is considered standard in the treatment of patients with relapsed or refractory aggressive peripheral T-cell lymphoma (PTCL). However, the optimal salvage regimen before ASCT has not yet been established. Methods: We retrospectively analyzed 31 patients with relapsed or refractory aggressive PTCL after anthracycline based first-line chemotherapy who received either DexaBEAM (n=16) or ICE (n=15) regimen as first salvage chemotherapy followed by HDT and ASCT between 1996 and 2009. The median patient age was 46 years (range, 18-66) in the DexaBEAM group and 40 years (range, 17-59) in the ICE group. Patients were included independent of WHO stage and IPI score. Results: The overall response rate (OR) was significantly higher for patients treated with DexaBEAM (69%) as compared to the ICE group (20%; P=0.01), with higher complete response (CR; 38% vs. 7%) as well as partial response (PR; 31% vs. 13%) rate. Changing regimen due to failure of the first salvage therapy, 12 patients initially receiving ICE still achieved an OR of 58% (33% CR, 25% PR) with DexaBEAM as second salvage therapy, whereas in 3 patients receiving ICE after DexaBEAM failure only 1 patient achieved an OR (1 PR). Median progression-free survival (PFS) was significantly higher in the DexaBEAM group (6.4 vs. 2 months; P=0.01). Median overall survival (OS) was not different between the two groups (22.8 vs. 29.8 months; P=0.72), most likely due to the good response rate of patients to DexaBEAM as 2nd salvage regimen after failure of ICE chemotherapy. Major adverse event in both groups was myelosuppression with higher but tolerable treatment-related toxicity for patients in the DexaBEAM group. Conclusions: In this retrospective comparison DexaBEAM salvage chemotherapy was superior to ICE for patients with relapsed or refractory aggressive PTCL for remission induction prior to autologous transplantation, with higher but manageable treatment-related toxicity.