No abstract

Chronic myeloid leukemia (CML)-study IV was designed to explore whether treatment with imatinib (IM) at 400 mg/day (n=400) could be optimized by doubling the dose (n=420), adding interferon (IFN) (n=430) or cytarabine (n=158) or using IM after IFN-failure (n=128). From July 2002 to March 2012, 1551 newly diagnosed patients in chronic phase were randomized into a 5-arm study. The study was powered to detect a survival difference of 5% at 5 years. After a median observation time of 9.5 years, 10-year overall survival was 82%, 10-year progression-free survival was 80% and 10-year relative survival was 92%. Survival between IM400 mg and any experimental arm was not different. In a multivariate analysis, risk group, major-route chromosomal aberrations, comorbidities, smoking and treatment center (academic vs other) influenced survival significantly, but not any form of treatment optimization. Patients reaching the molecular response milestones at 3, 6 and 12 months had a significant survival advantage. For responders, monotherapy with IM400 mg provides a close to normal life expectancy independent of the time to response. Survival is more determined by patients’ and disease factors than by initial treatment selection. Although improvements are also needed for refractory disease, more life-time can currently be gained by carefully addressing non-CML determinants of survival.

The detection and identification of retroviral transcripts in brain samples, cerebrospinal fluid, and plasma of individuals with recent-onset schizophrenia and schizoaffective disorders suggest that activation or upregulation of distinct human endogenous retroviruses (HERVs) may play a role in the etiopathogenesis of neuropsychiatric diseases. To test this hypothesis, we performed a comprehensive microarray-based analysis of HERV transcriptional activity in human brains. We investigated 50 representative members of 20 HERV families in a total of 215 brain samples derived from individuals with schizophrenia or bipolar disorders and matched controls. A characteristic brain-specific retroviral activity profile was found that consists of members of the class I families HERV-E, HERV-F, and ERV9 and members of HERV-K taxa. In addition to these constitutively expressed HERVs, a number of differentially active HERV elements were identified in all brain samples independent of the disease pattern that may reflect differences in the genetic background of the tested individuals. Only a subgroup of the HML-2 family (HERV-K10) was significantly overrepresented in both bipolar-disorder-and schizophrenia-associated samples compared to healthy brains, suggesting a potential association with disease. Real-time PCR analysis of HERV env transcripts with coding capacity potentially involved in neuroinflammatory conditions revealed that env expression of HERV-W, HERV-FRD, and HML-2 remains unaffected regardless of the clinical picture. Our data suggest that HERV transcription in brains is weakly correlated with schizophrenia and related diseases but may be influenced by the individual genetic background, brain-infiltrating immune cells, or medical treatment.

Background: A significant proportion of the human genome is comprised of human endogenous retroviruses (HERVs). HERV transcripts are found in every human tissue. Expression of proviruses of the HERV-K(HML-2) family has been associated with development of human tumors, in particular germ cell tumors (GCT). Very little is known about transcriptional activity of individual HML-2 loci in human tissues, though.

No abstract

A prospective multicenter study was performed to investigate the clinical and molecular results of intensified double induction therapy including high-dose cytarabine (ara-C) in combination with ATRA in newly diagnosed acute promyelocytic leukemia (APL), followed by consolidation and 3 years maintenance therapy.

The increasing incidence of invasive fungal infections (IFI) in immunocompromised patients

The increasing incidence of aspergillosis, a life-threatening infection in immunocompromised patients, emphasizes the need to improve the currently limited diagnostic tools. We developed a two-step PCR assay that specifically amplifies a region of the 18S rRNA gene that is highly conserved in Aspergillus species. A number of primers with the least homology to equivalent human orCandida gene sequences were screened for the pairs that gave the highest sensitivity and specificity. No cross-reaction with the wide range of fungal and bacterial pathogens so far tested was observed. This assay allows direct and rapid detection of down to 10 fg of Aspergillus DNA corresponding to 1 to 5 CFU per ml of blood. A total of 315 blood and bronchoalveolar lavage samples from 140 subjects, including 93 patients at risk for invasive fungal disease, were screened. The result was a 100% correlation between positive histology, culture, or high-resolution computed tomography findings and PCR results. The test specificity was 89%. Our data point to the considerable potential clinical value of this simple, specific, rapid, and inexpensive PCR assay for improving the means of early diagnosis of systemic aspergillosis in high-risk patients.