Increased expression of platelet derived growth factor receptor ß on trephine biopsies correlates with advanced myeloma.

PURPOSE: Multiple myeloma (MM), a major cause of cancer mortality, is considered the second most frequent haematological malignancy in Europe. Angiogenesis is a multifactorial process that drives the tumorigenesis in solid tumors and in MM. The platelet derived growth factor (PDGF) receptors are cell surface tyrosine kinase receptors and play an important role in angiogenesis, cancer cell proliferation and dissemination. Few studies have been conducted regarding the expression of PDGF receptors and the correlation with clinical-pathological parameters and prognosis in MM. The purpose of our study was to evaluate, for the first time, in a large cohort of newly-diagnosed MM (NDMM) patients, the expression of PDGF receptor α and ß (PDGFR α, ß) in bone marrow trephine biopsies and investigate the association of PDGFR α, PDGFR ß with angiogenesis in the bone marrow, assessed by bone marrow microvessel density (MVD), clinical characteristics and prognosis. METHODS: In this retrospective study, we assessed the relation of PDGFR α and PDGFR ß immunohistochemical expression with MVD in formalin-fixed paraffin-embedded bone marrow sections from 120 NDMM patients. The immunoreactivity of PDGFR α and ß was examined on the basis of positive plasma cells (PCs) with specific cut off values. RESULTS: PDGFRα and PDGFRß were frequently expressed on malignant PCs. We found that increased PDGFRß expression was strongly associated with advanced disease and adverse prognosis. The expression of PDGFRα and MDV were not correlated with specific features. CONCLUSION: This analysis showed highly expressed PDGFRα and ß PCs of NDMM patients and indicated that high PDGFRß expression at diagnosis was associated with advanced-stage disease.

RAS mutation prevalence among patients with metastatic colorectal cancer: a meta-analysis of real-world data.

AIM: A confirmed wild-type RAS tumor status is commonly required for prescribing anti-EGFR treatment for metastatic colorectal cancer. This noninterventional, observational research project estimated RAS mutation prevalence from real-world sources. MATERIALS & METHODS: Aggregate RAS mutation data were collected from 12 sources in three regions. Each source was analyzed separately; pooled prevalence estimates were then derived from meta-analyses. RESULTS: The pooled RAS mutation prevalence from 4431 tumor samples tested for RAS mutation status was estimated to be 43.6% (95% CI: 38.8-48.5%); ranging from 33.7% (95% CI: 28.4-39.3%) to 54.1% (95% CI: 51.7-56.5%) between sources. CONCLUSION: The RAS mutation prevalence estimates varied among sources. The reasons for this are not clear and highlight the need for further research.

The effect of prolonged administration of hydroxyurea on morbidity and mortality in adult patients with sickle cell syndromes: results of a 17-year, single-center trial (LaSHS).

The aim of this prospective study was to evaluate the long-term efficacy and safety of hydroxyurea (HU) in patients with sickle cell disease (SCD). Thirty-four patients with sickle cell anemia (hemoglobin S [HbS]/HbS), 131 with HbS/beta(0)-thal, and 165 with HbS/beta(+)-thal participated in this trial. HU was administered to 131 patients, whereas 199 patients were conventionally treated. The median follow-up period was 8 years for HU patients and 5 years for non-HU patients. HU produced a dramatic reduction in the frequency of severe painful crises, transfusion requirements, hospital admissions, and incidence of acute chest syndrome. The probability of 10-year survival was 86% and 65% for HU and non-HU patients, respectively (P = .001), although HU patients had more severe forms of SCD. The 10-year probability of survival for HbS/HbS, HbS/beta (0)-thal, and HbS/IVSI-110 patients was 100%, 87%, and 82%, respectively, for HU patients and 10%, 54%, and 66%, for non-HU patients. The multivariate analysis showed that fetal hemoglobin values at baseline and percentage change of lactate dehydrogenase between baseline and 6 months were independently predicted for survival in the HU group. These results highlight the beneficial effect of HU, which seems to modify the natural history of SCD and raise the issue of expanding its use in all SCD patients.

Serum Dickkopf-1 is increased and correlates with reduced bone mineral density in patients with thalassemia-induced osteoporosis. Reduction post-zoledronic acid administration.

Dickkopf-1 is an inhibitor of Wnt signaling, which is crucial for osteoblast differentiation. We evaluated serum levels of Dickkopf-1 in 66 patients with thalassemia-induced osteoporosis who received therapy with zoledronic acid in a placebo-controlled, randomized trial. At baseline, thalassemia patients had increased serum levels of Dickkopf-1 that correlated with reduced bone mineral density of the lumbar spine and the distal radius. High Dickkopf-1 also correlated with increased bone resorption and reduced bone formation markers. Zoledronic acid produced a reduction in serum Dickkopf-1, which was associated with bone mineral density increase after 12 months of therapy. On the contrary, placebo group showed a borderline increase of Dickkopf-1, which was higher in patients who showed deterioration in pain scores. These results suggest that Dickkopf-1 is implicated in the pathogenesis of osteoporosis in thalassemia and reveal Dickkopf-1 as a possible target for the development of novel agents for the management of thalassemia-induced osteoporosis.

Is there a meaningful serum hepatitis B virus DNA cutoff level for therapeutic decisions in hepatitis B e antigen-negative chronic hepatitis B virus infection?

UNLABELLED: The diagnosis of hepatitis B e antigen (HBeAg)-negative chronic hepatitis B indicating therapeutic intervention currently requires serum hepatitis B virus (HBV) DNA >or=2,000 IU/mL. We evaluated the severity of liver histology and the presence of histological indication for treatment in patients with HBeAg-negative chronic HBV infection focusing on those with low viremia and/or normal alanine aminotransferase (ALT). In total, 399 patients with increased ALT and detectable serum HBV DNA (chronic hepatitis B patients) and 35 cases with persistently normal ALT and HBV DNA >2,000 IU/mL (inactive carriers) were included. Histological indication for treatment (grading score >or=7 and/or stage >or=2 in Ishak's classification) was found in 91% (185/203), 82% (75/91), 75% (47/63), and 62% (26/42) of chronic hepatitis B patients with HBV DNA >or=200,000, 20,000-199,999, 2,000-19,999, and <2,000 IU/mL, respectively (P < 0.001). Histological indication for treatment was more frequent in chronic hepatitis B patients with persistently elevated ALT (86% or 275/321), but it was also found in 74% (58/78) of those with transiently normal ALT (P = 0.025). All inactive carriers had HBV DNA <20,000 IU/mL. Histological indication for treatment was present in 17% (6/35) of inactive carriers always due to moderate (stage 2) fibrosis without active necroinflammation. CONCLUSION: HBeAg-negative chronic HBV patients with persistently or transiently increased ALT and HBV DNA >or=20,000 IU/mL almost always require therapeutic intervention, but histological indications for treatment are also present in the majority of such cases with HBV DNA <20,000 and even <2,000 IU/mL. In contrast, minimal histological lesions are observed in the majority of HBeAg-negative patients with persistently normal ALT and HBV DNA >2,000 IU/mL, who may not require immediate liver biopsy and treatment but only close follow-up.