Refine
Year of publication
- 2019 (4) (remove)
Document Type
- Article (4)
Language
- English (4)
Has Fulltext
- yes (4)
Is part of the Bibliography
- no (4)
Keywords
- Chemotherapy (4) (remove)
Institute
- Medizin (4)
Autologous hematopoietic stem cell transplantation (auto-HSCT) provides a potentially curative treatment option for relapsed and refractory lymphomas. Obesity displays an emerging epidemic risk factor for global mortality and is associated with an increased mortality in cancer patients. To date, the impact of obesity on the outcome of lymphoma patients undergoing auto-HSCT is understudied. We conducted a retrospective single-center study assessing 119 lymphoma patients who underwent auto-HSCT. Overall survival (OS) served as the primary endpoint whereas progression free survival (PFS), cumulative incidence of non-relapse related mortality (NRM) and cumulative incidence of relapse were analyzed as secondary endpoints. Obese patients (Body mass index, BMI≥30) had significantly lower OS (45.3% vs. 77.9%; p = 0.005) and PFS (29.8% vs. 67.2%; p<0.001) compared to non-obese patients at 48 months post-transplantation. The cumulative incidence of NRM displayed no significant differences while the cumulative incidence of relapse was significantly increased in patients with BMI≥30 (66.2% vs. 21.5%; p<0.001). Patients with a BMI<25 and overweight patients (BMI 25–30; 76.1% vs. 80.9%; p = 0.585), showed no significant difference in OS, whereas patients with BMI≥30 exhibited significant lower OS when compared to either of both groups (76.1% vs. 45.3%; p = .0.021 and 80.9% vs. 45.3%; p = 0.010). Furthermore, in a multivariate analysis, obesity was identified as an independent risk factor for death (Hazard ratio 2.231; 95% CI 1.024 to 4.860; p = 0.043). Further studies are needed to evaluate the reasons for the higher relapse rate causing higher mortality in obese patients.
Introduction: Vacuolization is a frequently found morphological feature in acute myeloid leukemia (AML) blasts. Subcellular origin and biological function as well as prognostic impact are currently unknown. The aim of this study was to evaluate whether vacuolization correlates with clinically relevant AML features.
Materials & methods: Bone marrow smears of patients diagnosed with AML at the University Hospital Frankfurt between January 2011 and August 2013 were analyzed for blast vacuolization and correlated with clinically relevant AML features. Patients undergoing standard induction chemotherapy were further analyzed for molecular and cytogenetic features as well as treatment response and survival.
Results: 14 of 100 patients diagnosed with AML receiving standard induction chemotherapy had evidence of blast vacuolization. Positivity for vacuolization correlated with a CD15 positive immunophenotype and with a higher incidence of high-risk AML according to the European LeukemiaNet risk stratification. AML patients with blast vacuolization had a poor blast clearance after standard induction chemotherapy and poor survival.
Discussion: In conclusion, our findings demonstrate that vacuolization can easily be determined in myeloid leukemia blasts and may be a useful biomarker to predict AML risk groups as well as early treatment response rates and survival.
Background/Aims: Hepatocellular carcinoma (HCC) represents the second most common cause of cancer-related deaths worldwide, not least due to its high chemoresistance. The long non-coding RNA nuclear paraspeckle assembly transcript 1 (NEAT1), localised in nuclear paraspeckles, has been shown to enhance chemoresistance in several cancer types. Since data on NEAT1 in HCC chemosensitivity are completely lacking and chemoresistance is linked to poor prognosis, we aimed to study NEAT1 expression in HCC chemoresistance and its link to HCC prognosis.
Methods: NEAT1 expression was determined in either sensitive, or sorafenib, or doxorubicin resistant HepG2, PLC/PRF/5, and Huh7 cells by qPCR. Paraspeckles were detected by immunostaining of paraspeckle component 1 (PSPC1) in cell culture and in a cohort of HCC patients. PSPC1 expression was correlated with clinical data. The expression of transcript variants of NEAT1 and transcripts encoding the paraspeckle-associated proteins was analysed in the TCGA liver cancer data set.
Results: NEAT1 was overexpressed in all three sorafenib and doxorubicin resistant cell lines. Paraspeckles were present in all chemoresistant cells, whereas no signal was detected in the sensitive cells. Expression of NEAT1 transcripts as well as transcripts encoding PSPC1, NONO, and RBM14 was increased in tumour tissue. Expression of PSPC1, NONO, and RBM14 transcripts was significantly associated with poor survival, whereas NEAT1 expression was not. Immunohistochemical analysis revealed that nuclear and cytoplasmic PSPC1-positivity was significantly associated with shorter overall survival of HCC patients.
Conclusion: Our data show an induction of NEAT1 in HCC chemoresistance and a high correlation of transcripts encoding paraspeckle-associated proteins with poor survival in HCC. Therefore, NEAT1, PSPC1, NONO, and RBM14 might be promising targets for novel HCC therapies, and the paraspeckle-associated proteins might be clinical markers and predictors for poor survival in HCC.
Introduction: The global spread of multidrug-resistant organisms (MDRO) complicates treatment and isolation measures in hospitals and has shown to increase mortality. Patients with disease- or therapy-related immunodeficiency are especially at risk for fatal infections caused by MDRO. The impact of MDRO colonization on the clinical course of AML patients undergoing intensive induction chemotherapy—a potentially curative but highly toxic treatment option—has not been systematically studied.
Materials & methods: 312 AML patients undergoing intensive induction chemotherapy between 2007 and 2015 were examined for MDRO colonization. Patients with evidence for MDRO before or during the hospital stay of induction chemotherapy were defined as colonized, patients who never had a positive swab for MDRO were defined as noncolonized.
Results: Of 312 AML patients 90 were colonized and 130 were noncolonized. Colonized patients suffered from significantly more days with fever, spent more days on the intensive care unit and had a higher median C-reactive protein value during the hospital stay. These findings did not result in a prolonged length of hospital stay or an increased mortality rate for colonized patients. However, in a subgroup analysis, patients colonized with carbapenem-resistant enterobacteriaceae (CRE) had a significantly reduced 60- and 90-day, as well as 1- and 2-year survival rates when compared to noncolonized patients.
Conclusion: Our analysis highlights the importance of intensive MDRO screening especially in patients with febrile neutropenia since persisting fever can be a sign of MDRO-colonization. CRE-colonized patients require special surveillance, since they seem to be at risk for death.