The authors describe a 21-year-old man with long-lasting Evans syndrome refractory to corticosteroids and immunosuppressive agents; the patient responded to four weekly infusions of rituximab. The patient relapsed with thrombocytopenia 7 months post-therapy and was successfully re-treated with two weekly doses of the same monoclonal antibody. He remains in remission for 7-plus months after the second treatment. Therapy was well tolerated, and no infectious complications occurred, despite avoiding administration of prophylactic gammaglobulin. Rituximab appears safe and modestly effective in a variety of immune-mediated hematologic diseases, including autoimmune hemolytic anemia, chronic immune thrombocytopenia, Evans syndrome, pure red cell aplasia, mixed type II cryoglobulinemia, cold agglutinin disease, and Waldenströ m's macroglobulinemia. However, as most of the published literature consists of case reports and small case series, international collaboration is essential in order to better define the efficacy and safety of this agent in children and adults with hematologic diseases. Am.

BackgroundInformation extraction from microarrays has not yet been widely used in diagnostic or prognostic decision-support systems, due to the diversity of results produced by the available techniques, their instability on different data sets and the inability to relate statistical significance with biological relevance. Thus, there is an urgent need to address the statistical framework of microarray analysis and identify its drawbacks and limitations, which will enable us to thoroughly compare methodologies under the same experimental set-up and associate results with confidence intervals meaningful to clinicians. In this study we consider gene-selection algorithms with the aim to reveal inefficiencies in performance evaluation and address aspects that can reduce uncertainty in algorithmic validation.ResultsA computational study is performed related to the performance of several gene selection methodologies on publicly available microarray data. Three basic types of experimental scenarios are evaluated, i.e. the independent test-set and the 10-fold cross-validation (CV) using maximum and average performance measures. Feature selection methods behave differently under different validation strategies. The performance results from CV do not mach well those from the independent test-set, except for the support vector machines (SVM) and the least squares SVM methods. However, these wrapper methods achieve variable (often low) performance, whereas the hybrid methods attain consistently higher accuracies. The use of an independent test-set within CV is important for the evaluation of the predictive power of algorithms. The optimal size of the selected gene-set also appears to be dependent on the evaluation scheme. The consistency of selected genes over variation of the training-set is another aspect important in reducing uncertainty in the evaluation of the derived gene signature. In all cases the presence of outlier samples can seriously affect algorithmic performance.ConclusionMultiple parameters can influence the selection of a gene-signature and its predictive power, thus possible biases in validation methods must always be accounted for. This paper illustrates that independent test-set evaluation reduces the bias of CV, and case-specific measures reveal stability characteristics of the gene-signature over changes of the training set. Moreover, frequency measures on gene selection address the algorithmic consistency in selecting the same gene signature under different training conditions. These issues contribute to the development of an objective evaluation framework and aid the derivation of statistically consistent gene signatures that could eventually be correlated with biological relevance. The benefits of the proposed framework are supported by the evaluation results and methodological comparisons performed for several gene-selection algorithms on three publicly available datasets.

The authors describe a 4-year-old girl with acute lymphoblastic leukemia in remission who developed fulminant hepatic failure due to varicella-zoster virus (VZV). Diagnosing VZV visceral infection in immunocompromised patients is often difficult due to atypical clinical presentation with few or no skin lesions and severe abdominal or back pain. Prompt initiation of empirical treatment with acyclovir and VZV immunoglobulin pending results of the serum polymerase chain reaction for VZV is warranted in this clinical setting.

Thrombophilic traits were relatively common in this group of native Cretan children treated for malignancy. Thromboprophylaxis should be considered in Cretan children in the presence of known acquired risk factors for thrombosis, but a larger prospective to study is first needed.

We present the unusual case of a 16-year-old girl with T-cell acute lymphoblastic leukemia (ALL) with an early thymocyte immunophenotype without myeloid markers, who after 13 months of complete hematological remission relapsed as acute myelogenous leukemia (AML) with minimal differentiation and died of her disease. Whether the AML represented a relapse with lineage switch of the original immature T-cell clone or a new secondary malignancy, could not be proven due to the absence of molecular or clonal markers. This report suggests that a subset of CD7+ T-cell leukemias without mature T-cell antigens (CD4-, CD8-) are minimally differentiated and can relapse as AML.