The Dohner fluorescence in situ hybridization prognostic classification of chronic lymphocytic leukaemia (CLL): the CLL Research Consortium experience.

This study revisited the Dohner prognostic hierarchy in a cohort of 1585 well-documented patients with chronic lymphocytic leukaemia. The duration of both time to first treatment (TTFT) and overall survival (OS) were significantly longer than observed previously, and this is at least partly due to improved therapeutic options. Deletion 13q remains the most favourable prognostic group with median TTFT and OS from fluorescence in situ hybridization (FISH) testing of 72 months and >12 years, respectively.

Validation of ZAP-70 methylation and its relative significance in predicting outcome in chronic lymphocytic leukemia.

ZAP-70 methylation 223 nucleotides downstream of transcription start (CpG+223) predicts outcome in chronic lymphocytic leukemia (CLL), but its impact relative to CD38 and ZAP-70 expression or immunoglobulin heavy chain variable region (IGHV) status is uncertain. Additionally, standardizing ZAP-70 expression analysis has been unsuccessful. CpG+223 methylation was quantitatively determined in 295 untreated CLL cases using MassARRAY.

The TOKEn project: knowledge synthesis for in silico science.

Objective: The conduct of investigational studies that involve large-scale data sets presents significant challenges related to the discovery and testing of novel hypotheses capable of supporting in silico discovery science. The use of what are known as Conceptual Knowledge Discovery in Databases (CKDD) methods provides a potential means of scaling hypothesis discovery and testing approaches for large data sets. Such methods enable the high-throughput generation and evaluation of knowledge-anchored relationships between complexes of variables found in targeted data sets.

The TRITON Project: Design and Implementation of an Integrative Translational Research Information Management Platform.

Multi-site consortia have become the preferred setting for team-based translational research programs. Such consortia are able to facilitate increased breadth and depth of basic science and clinical research activities, but also present numerous challenges related to data collection, analysis, storage, and exchange. The Chronic Lymphocytic Leukemia (CLL) Research Consortium (CRC), a s a prototypical instance of such a consortia, uses numerous loosely coupled web applications to address its informatics needs.

Standardization of fluorescence in situ hybridization studies on chronic lymphocytic leukemia (CLL) blood and marrow cells by the CLL Research Consortium.

Five laboratories in the Chronic Lymphocytic Leukemia (CLL) Research Consortium (CRC) investigated standardizing and pooling of fluorescence in situ hybridization (FISH) results as a collaborative research project. This investigation used fixed bone marrow and blood cells available from previous conventional cytogenetic or FISH studies in two pilot studies, a one-day workshop, and proficiency test. Multiple FISH probe strategies were used to detect 6q-, 11q-, +12, 13q-, 17p-, and IGH rearrangements.

Stimulation of chronic lymphocytic leukemia cells with CpG oligodeoxynucleotide gives consistent karyotypic results among laboratories: a CLL Research Consortium (CRC) Study.

Cytogenetic abnormalities are important prognostic indicators in CLL. Historically, only interphase cytogenetics was clinically useful in CLL, because traditional mitogens are not effective mitotic stimulants. Recently, CpG-oligodeoxynucleotide (ODN) stimulation has shown effectiveness in CLL cells.

Self-administered, subcutaneous alemtuzumab to treat residual disease in patients with chronic lymphocytic leukemia.

Background: Alemtuzumab is highly effective at treating chronic lymphocytic leukemia (CLL) in bone marrow, which is the usual site of residual disease after fludarabine-based treatment. Eliminating residual disease potentially is associated with longer remission and overall survival. The authors of this report evaluated the ability of subcutaneous alemtuzumab to treat residual disease.

Supporting the design of translational clinical studies through the generation and verification of conceptual knowledge-anchored hypotheses.

The ability to generate hypotheses based upon the contents of large-scale, heterogeneous data sets is critical to the design of translational clinical studies. In previous reports, we have described the application of a conceptual knowledge engineering technique, known as constructive induction (CI) in order to satisfy such needs. However, one of the major limitations of this method is the need to engage multiple subject matter experts to verify potential hypotheses generated using CI.

Integrating web portlet technologies with caGrid to enable rapid application development: the CRC Patient Study Calendar.

The caGrid middleware provides an extensible platform for the integration of heterogeneous data sources and services; such as those found in geographically distributed research consortia. We describe an architectural approach to the integration of web portlet technologies with caGrid in order to facilitate the rapid development of highly usable presentation models for grid-based data sources and services, using the development of a patient study calendar for the CLL Research Consortium as a motivating use case.

Relative value of ZAP-70, CD38, and immunoglobulin mutation status in predicting aggressive disease in chronic lymphocytic leukemia.

Leukemia-cell expression of ZAP-70, CD38, or unmutated immunoglobulin heavy chain variable region genes (U-IGHV) each is associated with aggressive disease in patients with chronic lymphocytic leukemia (CLL). To assess the relative strength of each marker, we defined thresholds for designating a case as positive for CD38 or ZAP-70 in a test cohort of 307 patients and used these data-defined criteria to stratify patients in an independent cohort of 705 patients. Multivariable analysis revealed that ZAP-70 was the strongest risk factor.

Use of IGHV3-21 in chronic lymphocytic leukemia is associated with high-risk disease and reflects antigen-driven, post-germinal center leukemogenic selection.

We examined the chronic lymphocytic leukemia (CLL) cells of 2457 patients evaluated by the CLL Research Consortium (CRC) and found that 63 (2.6%) expressed immunoglobulin (Ig) encoded by the Ig heavy-chain-variable-region gene (IGHV), IGHV3-21. We identified the amino acid sequence DANGMDV (motif-1) or DPSFYSSSWTLFDY (motif-2) in the Ig heavy-chain (IgH) third complementarity-determining region (HCDR3) of IgH, respectively, used by 25 or 3 cases.

Ontology-anchored Approaches to Conceptual Knowledge Discovery in a Multi-dimensional Research Data Repository.

Chronic Lymphocytic Leukemia (CLL) is the most common adult leukemia in the U.S., and is currently incurable.

CRC Clinical Trials Management System (CTMS): an integrated information management solution for collaborative clinical research.

The Chronic Lymphocytic Leukemia (CLL) Research Consortium (CRC) consists of 9 geographically distributed sites conducting a program of research including both basic science and clinical components. To enable the CRC's clinical research efforts, a system providing for real-time collaboration was required. CTMS provides such functionality, and demonstrates that the use of novel data modeling, web-application platforms, and management strategies provides for the deployment of an extensible, cost effective solution in such an environment.

CRC Tissue Core Management System (TCMS): integration of basic science and clinical data for translational research.

The Chronic Lymphocytic Leukemia (CLL) Research Consortium (CRC) consists of 9 geographically distributed sites conducting a program of research including both basic science and clinical components. The CRC TCMS was designed to capture and integrate basic science and clinical data sets. The system utilizes multiple data modeling methodologies and web-application platforms, and was designed with the high level objectives of providing an extensible, generalizable model for integrating data as required to conduct translational research.