Management of high-risk myelodysplastic syndromes.

The myelodysplastic syndromes (MDS) are a group of clonal disorders characterized by one or more cytopenias secondary to bone marrow dysfunction. The percentage of bone marrow blasts, the number of cytopenic cell lines and cytogenetics define more precisely clinical risk groups. In the high-risk MDS, the time for evolution to acute myeloid leukemia (AML) is between 0.2 and 1.1 years and the median survival has been evaluated between 0.4 and 1.2 years. Progress in the understanding the biology of MDS and the development of accurate prognostic classification systems have allowed a risk-adapted treatment strategy in individual patients. Some high-risk MDS patient categories may benefit from intensive cytotoxic treatment. Allogeneic stem cell transplantation (alloSCT) from donors remains the treatment of choice for younger patients. Autologous stem cell transplantation (ASCT) may provide a suitable alternative for those patients without a sibling donor or for older patients' categories. New regimens using non-myeloablative stem cell transplantation followed by donor lymphocyte infusions (DLI) are underway and have achieved promising results in HLA-identical transplantation, resulting in reduced morbidity and mortality and confirming that this approach is feasible in patients ineligible for conventional allografting due to age and/or organ toxicity. Other therapeutic strategies include new low-dose treatments, antiapoptotic agents such as amifostine and anticytokine therapy, which are currently under investigation and deserve further evaluation. More insights into the biology of the disease, the discovery of new therapeutic approaches and the search for better ways to use existing strategies may lead to more effective treatments.

Vascular endothelial growth factor gene polymorphisms increase the risk to develop psoriasis.

We investigated the relationship between eight polymorphisms in the gene encoding for vascular endothelial growth factor (VEGF) (-1540C > A, -1512Ins18, -1451C > T, -460T > C, -160C > T, -152G > A, -116G > A and +405G > C) and plaque-type psoriasis stratified for age at onset, gender and family history of dermatosis. For this purpose, 117 patients with chronic plaque-type psoriasis and 215 healthy subjects were enrolled. We found that being homozygous -1540AA, -1512InsIns, -1451TT, -460CC and -152AA conferred a significant risk in developing psoriasis compared with heterozygous (-1540CA, -1512 + Ins, -1451CT, -460CT and -152AG) and homozygous genotypes (-1540CC, -1512 + +-1451CC, -460TT and -152GG) grouped together [odds ratio (ORs) = 1.73, 1.73, 1.73, 1.77 and 1.87, respectively]. Conversely, having the -116AA or +405GG genotype did not significantly increase the risk of disease expression compared with other genotypes of the same loci. Interestingly, we found that -1540AA, -1512InsIns, -1451TT, -460CC and -152AA homozygous genotypes have a significant two-fold increased risk in developing psoriasis after the age of 40 years (late-onset psoriasis) (ORs = 2.19, 2.19, 2.19, 2.05 and 2.26; P = 0.02, 0.02, 0.02, 0.04 and 0.02, respectively) as compared with controls. On the contrary, we found no phenotype-genotype association of the same magnitude among the patients in whom psoriasis developed at or before the age of 40 years (early-onset psoriasis) compared with controls. Genotype distributions were not significantly different when cases and controls were stratified either by gender or family history of psoriasis. Finally, VEGF plasma concentration was not significantly different between patients and controls and was not correlated with the severity of the disease.

[Invasive aspergillosis in the hematologic patient: the usefulness of computed tomographic and high-resolution computed tomographic studies]. / Aspetti dell'aspergillosi invasiva nel paziente ematologico: utilità dello studio mediante Tomografia Computerizzata e Tomografia Computerizzata ad alta risoluzione.

Invasive aspergillosis is an emerging cause of death in hematologic patients. Several patterns of lung involvement are described: acute tracheobronchitis, bronchopneumonia, pleural aspergillosis and angioinvasive aspergillosis. The latter pattern is the most common one; it is characterized by different signs, some of which, supported by clinical data, are quite suggestive for fungal etiology. Particularly, nodules and/or wedge-shaped lesions with a ground-glass halo are a useful early feature, best detected by HRCT. Early therapy with amphotericin B may improve survival chances. Therefore, in neutropenia patients we decided, when possible, to perform high-resolution computed tomography (HRCT) as soon as fever appears. This was feasible in 8 of 32 patients with invasive aspergillosis examined with HRCT. Immediate treatment with amphotericin B in one such patient showing a nodule with the halo sign allowed the lesion to completely disappear. The authors describe the frequency of different radiologic signs in 32 patients, as observed in 54 HRCT exams; the results are compared with those obtained with conventional CT and chest X-ray. Compared to chest X-ray, CT detects more lesions and is more sensitive to small pneumothorax and minimal pleural effusion or thickening. HRCT is more suitable to detect initial cavitation and thin ground-glass haloes.