Quantification of mitochondrial cfDNA reveals new perspectives for early diagnosis of colorectal cancer.

BACKGROUND: To unravel how the integrity of nuclear and mitochondrial circulating cell-free DNA (cfDNA) contributes to its plasma quantity in colorectal cancer (CRC) patients. METHODS: CfDNA from plasma samples of 80 CRC patients stratified by tumour stage and 50 healthy individuals were extracted. Total cfDNA concentration was determined and equal template concentrations (ETC) were analyzed by quantitative real-time PCR (qPCR) resulting in small and long fragments of KRAS, Alu and MTCO3. The obtained data was also examined relative to the total cfDNA concentration (NTC) and diagnostic accuracy was estimated using receiver operating characteristics. RESULTS: Total cfDNA levels were significantly higher in CRC group compared to healthy control and increased with tumour stage. Long nuclear fragment levels were significantly lower in CRC patients in ETC but not NTC condition. The integrity indices of nuclear cfDNA decreased from controls to patients with highly malignant tumor. Mitochondrial cfDNA fragment quantities were strongly reduced in early and late stages of tumor patients and prognostic value was higher in ETC. Predictive models based on either ETC or NTC predictor set showed comparable classification performance. CONCLUSION: Increased blood cfDNA concentration in late UICC stages inversely correlate with nuclear cfDNA integrity index and suggest that necrotic degradation is not a major cause for higher total cfDNA quantity. The diagnostic and prognostic value of MTCO3 is highly significant in early stages of CRC and can be evaluated more comprehensively, using ETC for qPCR analysis. TRIAL REGISTRATION: The study was registered retrospectively on DRKS, the german register for clinical trials (DRKS00030257, 29/09/2022).

Controlled non-randomised before-after study evaluating the impact of a focused recommendation card on vaccination rates of oncological patients-The Easy Vaccination in Oncology (EVO) strategy.

OBJECTIVE: By implementing a focused must-have vaccination strategy (Easy Vaccination in Oncology [EVO]), we aimed to increase rates for high-impact vaccinations (Streptococcus pneumoniae, influenza, herpes zoster and hepatitis B) in the at-risk population of oncological patients. METHODS: In this German multicentre interventional non-randomised controlled two-arm open trial with repeated cross-sectional data collection, we evaluated the EVO strategy as an easy to implement approach. Vaccination rates were assessed in the outpatient setting and re-assessed after 3 months. A generalised linear mixed model (GLMM) was used to assess the primary endpoint (Streptococcus pneumoniae vaccination rates according to recommendations), taking clustering within clinics into account. RESULTS: Vaccination rates substantially increased in the intervention group; Streptococcus pneumoniae +21.5% (+16.7% according to recommendations), influenza +12.2%, herpes zoster +13.3% (+13.6% age group 50+), and hepatitis B +11%. Vaccination rates in the control group tended to decrease or increase only moderately (-5.8% [-3.8%], +7.4%, +2.1% [1.4%], and -1.7%, respectively). GLMM showed significant effect of the intervention (OR 7.50, 95% CI 2.18-25.80, p = 0.001). CONCLUSION: This easy-to-implement and resource-saving approach has the potential to increase vaccination rates in oncological patients and to have a considerable impact protecting oncological patients from preventable infectious diseases. CLINICAL TRIAL REGISTRATION: The study was registered at the German Resister for Clinical Studies (DRKS) under DRKS00020118.

Herpes Zoster Vaccination Rates in Hematological and Oncological Patients-Stock Taking 2 Years after Market Approval.

BACKGROUND: Vaccinations have the potential to significantly lower the burden of disease for many major infections in the high-risk population of hematological and oncological patients. In this regard Shingrix®, an inactivated Varicella Zoster Virus vaccine, received market approval in the European Union in March 2018, after prior US approval in October 2017, and recommendations specifically state immunocompromised, including oncological, patients. As vaccination rates are considered to be poor in oncological patients, determining the current vaccination rates for Shingrix® two years after market approval is important in defining the need for intervention to bring this potentially high-impact vaccine to the patients. METHODS: We analyzed data of the EVO Study to provide data for Herpes zoster vaccination rates in oncological patients. The EVO Study was an interventional study evaluating the potential of increasing vaccination rates of specified must-have vaccinations by an instructional card in the oncological setting. Numbers presented in this publication merged baseline data and follow-up data of the control group; hence data not affected by the intervention. RESULTS: Data of 370 patients were analyzed; 21.1% with hematological malignancies and 78.9% with solid cancer. Only 3.0% were vaccinated with Shingrix®. Patients with hematological malignancy were more likely to be vaccinated than those with solid cancer (7.7 vs. 1.7%). CONCLUSION: Despite clear recommendations and a pressing need in the high-risk population of hematological and oncological patients, the vast majority of patients are still left without vaccine protection against Herpes zoster by Shingrix®.

A phenomenological three-parameter model for predicting the extent of outpatient palliative care.

Whether a patient receives general or specialized outpatient palliative cancer care rarely follows clear criteria, leading to undertreatment or overtreatment. Detailed scores exist to predict prognosis, but not treatment requirements, leaving caregivers to follow their intuition. As a phenomenological indicator incorporating possibly important subjective information, intuition may in fact be a helpful tool. In this prospective observational study, a score to estimate three global dimensions of patients' resources was applied: Medical prognosis, feeling of strength and feeling of support. The score results were correlated with the actual amount and effort of care required during the subsequent palliative care time. This phenomenological score correlated well with the performance index and the Hospice and Palliative care Evaluation score. Whilst various individual items correlated significantly with the score or its constituent parameters, there was no uniform coherent pattern, reflecting the complexity of palliative care and the potential value of this predictive tool.

Retrospective comparison of reinfusion procedures and subsequent leukopenia in autologous stem cell transplantation.

Standard operating procedures for autologous stem cell transplantation (SCT) aim to guarantee best possible engraftment. Three procedures are routinely used for transplant infusion: regular bag infusion (Procedure 1), injection via syringe (Procedure 2), and combination of regular bag infusion and syringe (Procedure 3). We conducted a retrospective analysis of all autologous stem cell transplants done in the hematology department of the Vivantes Clinic Neukoelln in Berlin, Germany, between January 1, 2016 and March 4, 2017. Of the total of 69 patients, 17 underwent Procedure 1, 32 Procedure 2, and 20 Procedure 3. Although speed of transplant reinfusion differed significantly between procedure types, these differences had no effect on duration of leukopenia. However, duration of leukopenia did correlate with need for blood transfusion and use of antibiotics. Our findings contradict the general perception that very rapid reinfusion is necessary. Nevertheless, considering the limitations of this study (retrospective, single center, small sample size) and that longer duration of aplasia is associated with greater need for intervention, efficient transplant reinfusion is advisable. More research is needed regarding timeliness and type of procedure used.

Genome-wide DNA methylation analysis pre- and post-lenalidomide treatment in patients with myelodysplastic syndrome with isolated deletion (5q).

Myelodysplastic syndrome (MDS) with isolated deletion of chromosome 5q (MDS del5q) is a distinct subtype of MDS with quite favorable prognosis and excellent response to treatment with lenalidomide. Still, a relevant percentage of patients do not respond to lenalidomide and even experience progression to acute myeloid leukemia (AML). In this study, we aimed to investigate whether global DNA methylation patterns could predict response to lenalidomide. Genome-wide DNA methylation analysis using Illumina 450k methylation arrays was performed on n=51 patients with MDS del5q who were uniformly treated with lenalidomide in a prospective multicenter trial of the German MDS study group. To study potential direct effects of lenalidomide on DNA methylation, 17 paired samples pre- and post-treatment were analyzed. Our results revealed no relevant effect of lenalidomide on methylation status. Furthermore, methylation patterns prior to therapy could not predict lenalidomide response. However, methylation clustering identified a group of patients with a trend towards inferior overall survival. These patients showed hypermethylation of several interesting target genes, including genes of relevant signaling pathways, potentially indicating the evaluation of novel therapeutic targets.

Prevalence and Course of IgA and IgG Antibodies against SARS-CoV-2 in Healthcare Workers during the First Wave of the COVID-19 Outbreak in Germany: Interim Results from an Ongoing Observational Cohort Study.

(1) Background: Healthcare workers (HCWs) are prone to intensified exposure to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in the ongoing pandemic. We prospectively analyzed the prevalence of antibodies against SARS-CoV-2 in HCWs at baseline and follow up with regard to clinical signs and symptoms in two university hospitals in Brandenburg, Germany. (2) Methods: Screening for anti-SARS-CoV-2 IgA and IgG antibodies was offered to HCWs at baseline and follow up two months thereafter in two hospitals of Brandenburg Medical School during the first wave of the COVID-19 pandemic in Germany in an ongoing observational cohort study. Medical history and signs and symptoms were recorded by questionnaires and analyzed. (3) Results: Baseline seroprevalence of anti-SARS-CoV-2 IgA was 11.7% and increased to 15% at follow up, whereas IgG seropositivity was 2.1% at baseline and 2.2% at follow up. The rate of asymptomatic seropositive cases was 39.5%. Symptoms were not associated with general seropositivity for anti-SARS-CoV-2; however, class switch from IgA to IgG was associated with increased symptom burden. (4) Conclusions: The seroprevalence of antibodies against SARS-CoV-2 was low in HCWs but higher compared to population data and increased over time. Screening for antibodies detected a significant proportion of seropositive participants cases without symptoms.

Risk to Radiology Staff for Occupational COVID-19 Infection in a High-Risk and a Low-Risk Region in Germany: Lessons from the "First Wave". / Risiko radiologischer Mitarbeiter für eine COVID-19-Infektion in einer Hoch- und Niedrigrisikoregion in Deutschland: Lehren aus der "ersten Welle".

PURPOSE: The recent COVID-19 pandemic has resulted in an increasing overload of the medical system. Healthcare workers (HCW) in radiology departments are exposed to a high infection risk similar to HCWs in the ICU or dedicated COVID wards. The goal of our paper is to evaluate the prevalence of IgG antibody against SARS-CoV-2 among radiology HCWs in two different hospitals and regions in Germany with a low and high COVID-19 prevalence and to compare it to the prevalence in other clinical personnel. Additionally, we assessed the number of radiological procedures performed in patients with a positive PCR test (C+) followed by a short review of the risk for nosocomial infections of radiology HCWs. MATERIALS AND METHODS: During the first COVID-19 wave between March and July 2020, we evaluated a region with one of the highest COVID-19 rates (776-1570/100 000) in Germany (Hospital A). Additionally, we assessed Hospital B in a region with a low prevalence (65/100 000). We tested the serum prevalence of SARS-CoV-2 IgG antibodies among the whole staff with a subgroup analysis for radiology in both hospitals. We calculated the total number of different radiological procedures performed in C+ patients. RESULTS: In Hospital A 594 PCR-proven C+ patients were treated resulting in 2723 radiological procedures. 24 % (n = 6) of the radiology technicians and 13.35 (n = 2) of radiologists had a positive IgG test. The rates were similar to positive rates in HCWs in COVID-19 wards and ICUs within the hospital. The most frequently performed procedures in C+ patients were chest X-rays (3.17/patient) and CT examinations (1.15/patient). In Hospital B 50 C+ patients were treated, resulting in 64 radiological procedures. None of the HCWs tested IgG positive. The most frequently performed examinations were also chest X-rays (1.04/patient) and CT (0.2/patient). CONCLUSION: HCWs in radiology have a high occupational infection risk similar to that of HCWs in ICUs and dedicated COVID wards. KEY POINTS: · The risk of acquiring COVID-19 increases with the amount of contact with infected individuals.. · The occupational risk of a SARS-CoV-2 infection for radiology staff is similar to that of nurses and physicians in COVID wards.. · Hygiene concepts and medical resources have to be adapted for further COVID outbreaks.. · Reporting of an occupational disease can be considered in the case of seropositive staff.. CITATION FORMAT: · Finkenzeller T, Lenhart S, Reinwald M et al. Risk to Radiology Staff for Occupational COVID-19 Infection in a High-Risk and a Low-Risk Region in Germany: Lessons from the "First Wave". Fortschr Röntgenstr 2021; 193: 537 - 543.

Aspergillus specific nested PCR from the site of infection is superior to testing concurrent blood samples in immunocompromised patients with suspected invasive aspergillosis.

Invasive aspergillosis (IA) is a severe complication in immunocompromised patients. Early diagnosis is crucial to decrease its high mortality, yet the diagnostic gold standard (histopathology and culture) is time-consuming and cannot offer early confirmation of IA. Detection of IA by polymerase chain reaction (PCR) shows promising potential. Various studies have analysed its diagnostic performance in different clinical settings, especially addressing optimal specimen selection. However, direct comparison of different types of specimens in individual patients though essential, is rarely reported. We systematically assessed the diagnostic performance of an Aspergillus-specific nested PCR by investigating specimens from the site of infection and comparing it with concurrent blood samples in individual patients (pts) with IA. In a retrospective multicenter analysis PCR was performed on clinical specimens (n = 138) of immunocompromised high-risk pts (n = 133) from the site of infection together with concurrent blood samples. 38 pts were classified as proven/probable, 67 as possible and 28 as no IA according to 2008 European Organization for Research and Treatment of Cancer/Mycoses Study Group consensus definitions. A considerably superior performance of PCR from the site of infection was observed particularly in pts during antifungal prophylaxis (AFP)/antifungal therapy (AFT). Besides a specificity of 85%, sensitivity varied markedly in BAL (64%), CSF (100%), tissue samples (67%) as opposed to concurrent blood samples (8%). Our results further emphasise the need for investigating clinical samples from the site of infection in case of suspected IA to further establish or rule out the diagnosis.

The evolving landscape of new diagnostic tests for invasive aspergillosis in hematology patients: strengths and weaknesses.

PURPOSE OF REVIEW: The diagnosis of invasive aspergillosis in hematologic patients is a complex composite of clinical preconditions and features, imaging findings, biomarker combinations from appropriate clinical samples and microbiological and/or histological findings. RECENT FINDINGS: Recent developments in the evolving landscape of diagnostic tests for invasive aspergillosis in adult hematology patients are highlighted. SUMMARY: Novel approaches and tools are currently under development. Focusing optimized diagnostic performance, in particular the combination of biomarkers from appropriate clinical samples, improved diagnostic performance distinctly.

Evaluating the use of PCR for diagnosing invasive aspergillosis.

INTRODUCTION: Aspergillus species, primarily Aspergillus fumigatus, are still the most emerging fungal pathogens. Within recent years, novel molecular methods have been developed to improve the diagnosis of life-threatening invasive aspergillosis in high risk patients. Especially patients with malignant hematological diseases undergoing intensive chemotherapy are at risk and mortality rates are exceptionally high, in part due to difficulties and delays in establishing a microbiologic diagnosis. Early diagnosis and treatment are crucial for an adequate therapeutical management, but, however, are hardly achieved in the clinical setting because most of the current conventional diagnostic tools either lack specificity or acceptable sensitivity at the critical early phase of the infection. Areas covered: To review the clinical value, advantages and problems as well as drawbacks of molecular approaches, especially polymerase chain reaction (PCR)-based assays to detect genomic DNA of Aspergillus species in clinical samples of immunocompromised, especially hematological patients at high risk for IA, a comprehensive review of the literature was performed and expert opinion was expressed. Expert commentary: The results of numerous attempts to diagnose invasive aspergillosis by PCR-based detection of fungal genome in clinical samples highlight the potential of the PCR technique to improve early diagnosis of invasive aspergillosis in patients with hematological malignancies during intensive antineoplastic treatment, combined with imaging surveillance and serologic diagnostic tools. Further comparative validation of reliable assays in prospective multicenter studies is mandatory and urgently needed in order to establish a harmonization and standardization, so that 'gold standard assays' may be incorporated into diagnostic and therapeutic algorithms that improve the prognosis of patients with life-threatening infections caused by Aspergillus species.

Galactomannan testing and Aspergillus PCR in same-day bronchoalveolar lavage and blood samples for diagnosis of invasive aspergillosis.

In recent years galactomannan antigen testing (GM) and also Aspergillus PCR have become increasingly important for diagnosis of invasive aspergillosis (IA). Whether or not these tests need to be performed with bronchoalveolar lavage fluid (BALF; i.e., primary site of infection), or testing of blood samples is sufficient, remains, however, a matter of debate. We evaluated the diagnostic performance of GM ELISA, and Aspergillus PCR by using BALF samples and blood samples obtained at the same day from a total of 53 immunocompromised patients (16 with probable/proven IA and 37 with no evidence of IA according to the revised EORTC/MSG criteria; 38 patients with hematological malignancies were prospectively enrolled at the Medical University of Graz, Austria, 15 patients with mixed underlying diseases at the Mannheim University Hospital). Patients with possible IA were excluded from this analysis. A total of 34/53 (64%) of all patients and 12/16 (75%) of patients with probable/proven IA received mold-active antifungal prophylaxis/therapy at the time of the BALF procedure. Sensitivities of GM and Aspergillus PCR were 38% and 44% in BALF, and 31% and 0% in blood, respectively. Best sensitivity (75%) for detecting proven/probable IA was achieved when BALF Aspergillus PCR, BALF GM (>1.0 ODI), BALF-culture and serum-GM (>0.5 ODI) were combined (specificity 95%). In conclusion, sensitivities of the evaluated diagnostic tests-when interpreted on their own-were low in BALF and even lower in blood, sensitivities increased markedly when diagnostic tests were combined.

Biomarker-based diagnostic work-up of invasive pulmonary aspergillosis in immunocompromised paediatric patients--is Aspergillus PCR appropriate?

Invasive aspergillosis (IA) is an important cause of morbidity and mortality in children and adults with haematologic malignancies or undergoing allogeneic haematopoietic stem cell transplantation, and early diagnosis and adequate antifungal treatment improve outcome. However, important differences exist between children and adults regarding epidemiology, underlying disease, and comorbidities, and the value of diagnostic tools to detect IA may also differ between these patient populations. Imaging studies are important to detect IA early, but typical findings of IA in chest computed tomography of adults are not detected in the majority of children. Whereas the value of the serum marker galactomannan seems to be comparable in children and adults, data on the performance of beta-d-glucan in children are too limited for firm conclusions. PCR-based assays are a promising diagnostic approach to rapidly and reliably detect and identify Aspergillus species in various clinical samples. However, as the majority of data on PCR-based approaches has been obtained in adult patients, the value of this method in paediatric patients has not been defined to date. The present review focuses on studies of PCR-based methods to diagnose IA in immunocompromised paediatric patients.

Direct comparison of galactomannan performance in concurrent serum and bronchoalveolar lavage samples in immunocompromised patients at risk for invasive pulmonary aspergillosis.

Invasive pulmonary aspergillosis (IPA) is a life-threatening infection mainly affecting immunocompromised patients. Early diagnosis is critical, but the diagnostic gold standard (histopathology and culture) is time consuming and cannot offer early confirmation of IPA. Fungal biomarkers like galactomannan (GM) are a promising extension to the diagnostic repertoire. However, it still remains under discussion if biomarker analysis from the site of the infection is superior to testing blood samples. We retrospectively evaluated the diagnostic performance of concurrent serum GM and bronchoalveolar lavage (BAL) GM (obtained within 24 h) of immunocompromised patients at high risk of IPA. Twenty-six proven/probable patients and eight patients with no IPA according to the EORTC/MSG 2008 criteria were included in this study. Sensitivity, specificity, positive predictive value, negative predictive value and diagnostic odds ratio were for BAL GM: 85%, 88%, 96%, 64% and 38.5, and for serum GM: 23%, 88%, 88%, 26% and 2.1 respectively. BAL GM proved to be significantly more sensitive for the detection of IPA compared to same-day serum GM in patients at high risk of IPA (P < 0.0001). Our data show that BAL GM testing is significantly superior to serum GM implying that diagnostic efforts should focus on specimens from the site of infection.

Influence of mould-active antifungal treatment on the performance of the Aspergillus-specific bronchoalveolar lavage fluid lateral-flow device test.

The effect of mould-active antifungal (AF) therapy/prophylaxis on the performance of the Aspergillus-specific lateral-flow device (LFD) test for diagnosing invasive pulmonary aspergillosis (IPA) was evaluated. This was a retrospective analysis of patients diagnosed with probable or proven IPA (according to revised EORTC/MSG criteria) at the Medical University of Graz (Austria) and the University Hospital of Mannheim (Germany) between February 2011 and December 2014. In total, 60 patients with 63 bronchoalveolar lavage fluid (BALF) samples were included in the analysis. Patient charts were reviewed regarding AF treatment at the time of bronchoscopy, and the influence of AFs on the performance of the LFD and BALF galactomannan (GM) ELISA results was calculated. Overall, 54 patients (57 BALF samples) had probable IPA and 6 patients (6 samples) had proven IPA. In 21/63 samples (33%) (from 19 patients), systemic mould-active AFs had been initiated before bronchoscopy. Of 63 BALF samples, 16 (25%) yielded a false-negative LFD result. The sensitivity of the LFD for probable/proven IPA was significantly lower in those receiving mould-active AFs compared with those without (52% vs. 86%; P=0.006). Similar results were found for BALF GM, with sensitivities decreasing under systemic AFs (71% vs. 95%, P=0.013 with the 0.5 ODI cut-off; 52% vs. 81%, P=0.036 with the 1.0 cut-off). These results suggest that the sensitivity of the BALF LFD and BALF GM assays may be reduced in the presence of mould-active AF treatment. Negative results in patients on AFs should therefore be interpreted with caution.

Functional protease profiling for laboratory based diagnosis of invasive aspergillosis.

Invasive aspergillosis (IA) remains difficult to diagnose in immunocompromised patients, because diagnostic criteria according to EORTC/MSG guidelines are often not met and have low sensitivity. Hence there is an urgent need to improve diagnostic procedures by developing novel approaches. In the present study, we present a proof of concept experiment for the monitoring of Aspergillus associated protease activity in serum specimens for diagnostic purpose. Synthetic peptides that are selectively cleaved by proteases secreted from Aspergillus species were selected from our own experiments and published data. These so called reporter peptides (RP, n=5) were added to serum specimens from healthy controls (HC, n=101) and patients with proven (IA, n=9) and possible (PIA, n=144) invasive aspergillosis. Spiked samples were incubated ex vivo under strictly standardized conditions. Proteolytic fragments were analyzed using MALDI-TOF mass spectrometry. Spiked specimens of IA patients had highest concentrations of RP-fragments followed by PIA and HC. The median signal intensity was 116.546 (SD, 53.063) for IA and 5.009 (SD, 8.432) for HC. A cut-off >36.910 was chosen that performed with 100% specificity and sensitivity. Patients with PIA had either values above [53% (76/144)] or below [47% (67/144)] this chosen cut-off. The detection of respective reporter peptide fragments can easily be performed by MALDI TOF mass spectrometry. In this proof of concept study we were able to demonstrate that serum specimens of patients with IA have increased proteolytic activity towards selected reporter peptides. However, the diagnostic value of functional protease profiling has to be validated in further prospective studies. It is likely that a combination of existing and new methods will be required to achieve optimal performance for diagnosis of IA in the future.

Multicenter evaluation of a lateral-flow device test for diagnosing invasive pulmonary aspergillosis in ICU patients.

INTRODUCTION: The incidence of invasive pulmonary aspergillosis (IPA) in intensive care unit (ICU) patients is increasing, and early diagnosis of the disease and treatment with antifungal drugs is critical for patient survival. Serum biomarker tests for IPA typically give false-negative results in non-neutropenic patients, and galactomannan (GM) detection, the preferred diagnostic test for IPA using bronchoalveolar lavage (BAL), is often not readily available. Novel approaches to IPA detection in ICU patients are needed. In this multicenter study, we evaluated the performance of an Aspergillus lateral-flow device (LFD) test for BAL IPA detection in critically ill patients. METHODS: A total of 149 BAL samples from 133 ICU patients were included in this semiprospective study. Participating centers were the medical university hospitals of Graz, Vienna and Innsbruck in Austria and the University Hospital of Mannheim, Germany. Fungal infections were classified according to modified European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria. RESULTS: Two patients (four BALs) had proven IPA, fourteen patients (sixteen BALs) had probable IPA, twenty patients (twenty-one BALs) had possible IPA and ninety-seven patients (one hundred eight BALs) did not fulfill IPA criteria. Sensitivity, specificity, negative predictive value, positive predictive value and diagnostic odds ratios for diagnosing proven and probable IPA using LFD tests of BAL were 80%, 81%, 96%, 44% and 17.6, respectively. Fungal BAL culture exhibited a sensitivity of 50% and a specificity of 85%. CONCLUSION: LFD tests of BAL showed promising results for IPA diagnosis in ICU patients. Furthermore, the LFD test can be performed easily and provides rapid results. Therefore, it may be a reliable alternative for IPA diagnosis in ICU patients if GM results are not rapidly available. TRIAL REGISTRATION: ClinicalTrials.gov NCT02058316. Registered 20 January 2014.

Risk of Infectious Complications in Hemato-Oncological Patients Treated with Kinase Inhibitors.

Infectious complications are a major cause of morbidity and mortality in patients with hemato-oncological diseases. Although disease-related immunosuppression represents one factor, aggressive treatment regimens, such as chemotherapy, stem cell transplantation, or antibody treatment, account for a large proportion of infectious side effects. With the advent of targeted therapies affecting specific kinases in malignant diseases, the outcome of patients has further improved. Nonetheless, dependent on the specific pathway targeted or off-target activity of the kinase inhibitor, therapy-associated infectious complications may occur. We review the most common and approved kinase inhibitors targeting a variety of hemato-oncological malignancies for their immunosuppressive potential and evaluate their risk of infectious side effects based on preclinical evidence and clinical data in order to raise awareness of the potential risks involved.

Prognostic importance of expression of the Wilms' tumor 1 gene in newly diagnosed acute promyelocytic leukemia.

Wilms' tumor 1 gene (WT1) is known to be highly expressed in acute promyelocytic leukemia (APL) but information on its impact on prognosis is lacking. WT1 expression was analyzed in bone marrow samples of 79 patients with APL at initial diagnosis. Patients had a differing outcome according to their level of WT1 expression. In patients who achieved a complete remission (CR), low or high WT1 expression was significantly associated with inferior overall survival (OS) compared to intermediate WT1 expression (49% for WT1high vs. 63% for WT1low vs. 93% for WT1int; p=0.008). Moreover, there were significant differences in relapse-free survival (RFS) between the three expression groups (42% for WT1high vs. 63% for WT1low vs. 83% for WT1int; p=0.047). In multivariable analysis WT1 expression showed an independent prognostic impact on OS of responders to induction therapy. In conclusion, the level of WT1 expression can add prognostic information in APL risk stratification.