Inflammatory and haematological markers in the maternal, umbilical cord and infant circulation in histological chorioamnionitis.

BACKGROUND: The relationship between histological chorioamnionitis and haematological and biochemical markers in mothers and infants at delivery, and in infants postnatally, is incompletely characterised. These markers are widely used in the diagnosis of maternal and neonatal infection. Our objective was to investigate the effects of histological chorioamnionitis (HCA) on haematological and biochemical inflammatory markers in mothers and infants at delivery, and in infants post-delivery. METHODS: Two hundred and forty seven mothers, delivering 325 infants, were recruited at the only tertiary perinatal centre in Western Australia. Placentae were assessed for evidence of HCA using a semi-quantitative scoring system. Maternal high sensitivity C-reactive protein (hsCRP), procalcitonin, and umbilical cord hsCRP, procalcitonin, white cell count and absolute neutrophil count were measured at delivery. In infants where sepsis was clinically suspected, postnatal CRP, white cell count and absolute neutrophil count were measured up to 48 hours of age. The effect of HCA on maternal, cord and neonatal markers was evaluated by multivariable regression analysis. RESULTS: The median gestational age was 34 weeks and HCA was present in 26 of 247 (10.5%) placentae. Mothers whose pregnancies were complicated by HCA had higher hsCRP (median 26 (range 2-107) versus 5.6 (0-108) mg/L; P<0.001). Histological chorioamnionitis was associated with higher umbilical cord hsCRP (75(th) percentile 2.91 mg/L (range 0-63.9) versus 75(th) percentile 0 mg/L (0-45.6); P<0.001) and procalcitonin (median 0.293 (range 0.05-27.37) versus median 0.064 (range 0.01-5.24) ug/L; P<0.001), with a sustained increase in neonatal absolute neutrophil count (median 4.5 (0.1-26.4)×10(9)/L versus 3.0 (0.1-17.8)×10(9)/L), and CRP up to 48 hours post-partum (median 10 versus 6.5 mg/L) (P<0.05 for each). CONCLUSION: Histological chorioamnionitis is associated with modest systemic inflammation in maternal and cord blood. These systemic changes may increase postnatally, potentially undermining their utility in the diagnosis of early-onset neonatal infection.

New drug therapies in peripheral T-cell lymphoma.

Peripheral T-cell lymphomas (PTCLs) are a heterogeneous collection of lymphomas that are associated with very poor prognosis. Conventional therapies, historically based on protocols for aggressive B-cell lymphomas, deliver less than adequate outcomes; the majority of patients experience early relapse after front-line treatment and current 5-year overall survival is only 10-30%. Clearly, new approaches are needed. In recent years there has been a plethora of novel agents showing activity in PTCL, often in patients with advanced relapsed or refractory disease. These agents include antifolate drugs (pralatrexate), histone deacetylase inhibitors (vorinostat, romidepsin, panobinostat and belinostat), nucleoside analogues (gemcitabine, forodesine and clofarabine), monoclonal antibodies (anti-CD52, anti-CD4 and anti-CD2), fusion toxins (denileukin diftitox), immunomodulatory agents (lenalidomide) and proteasome inhibitors (bortezomib). This is an exciting time in the treatment of PTCL, as our ever improving understanding of the distinguishing features, pathogenesis, molecular biology and progression of PTCL, and the knowledge of the mechanism and efficacy of novel therapies, may see a real improvement in outcomes for patients. The purpose of this article is to focus on these novel therapies and the results of recent clinical trials in PTCL.

The level of glycolytic metabolism in acute myeloid leukemia blasts at diagnosis is prognostic for clinical outcome.

This research investigated the level of glycolytic metabolism in leukemic blasts as a prognostic marker in AML. Using an in vitro dye-reduction assay, we determined the level of glycolytic metabolism in 26 BM samples taken from 23 adult patients with newly diagnosed (n=19) or relapsed (n=4) AML, and AML blasts stratified into two distinct cohorts of moderate (<70%) or high (>80%) levels of glycolytic metabolism. All samples taken at relapse were moderately glycolytic. However, nine of the 19 samples taken at diagnosis were highly glycolytic, and 10 were moderately glycolytic. Three patients had paired samples taken at diagnosis and relapse, and the glycolytic metabolism of these samples did not alter between the two time-points. The level of glycolytic metabolism did not correlate with the percentage of marrow blasts, patient age, or CG/molecular risk group. Highly glycolytic AML blasts were more resistant to apoptosis induced by ATRA and/or ATO in vitro, suggesting potential resistance to induction chemotherapy, as has been observed in solid tumors. Despite this, high levels of glycolytic metabolism at diagnosis were predictive of a significantly improved duration of CR1 and OS following AML remission induction chemotherapy. In conclusion, we found that the extent of myeloblast glycolysis may be an effective and easily applied method to determine the pretreatment prognosis of AML.