Biomedical subjects

Kevin White

Publications and source records attributed to Kevin White.

4 recordsLinked to original sources

PubMed2003

Results of triple therapy with interferon-alpha, cytarabine, and homoharringtonine, and the impact of adding imatinib to the treatment sequence in patients with Philadelphia chromosome-positive chronic myelogenous leukemia in early chronic phase.

BACKGROUND: Before the discovery of imatinib mesylate, a Bcr-Abl selective tyrosine kinase inhibitor, three agents, interferon-alpha (IFN-alpha), cytarabine (ara-C), and homoharringtonine (HHT), had demonstrated activity against Philadelphia chromosome (Ph)-positive chronic myelogenous leukemia (CML) as single agents and in couplet combinations. The goals of the current study were to evaluate the efficacy of the triple combination regimen with IFN-alpha, ara-C, and HHT in newly diagnosed Ph-positive CML and to assess the impact of the added sequential therapy with imatinib on overall prognosis. METHODS: Ninety patients with Ph-positive CML in early chronic phase received the triple regimen. Therapy consisted of 5 million units (MU)/m(2) IFN-alpha subcutaneously (s.c. daily, ara-C 10 mg s.c. daily, and HHT 2.5 mg/m(2) by continuous infusion over 24 hours daily x 5 every month. After a median duration of 16.5 months of therapy, 78 patients had their therapy changed to 400 mg orally administered imatinib daily. RESULTS: With the triple regimen, 85 patients (94%) achieved complete hematologic response and 67 patients (74%) had a cytogenetic response (Ph suppression to < or = 90%) which was complete (Ph 0%) in 20 patients (22%) and major in 42 patients (46%). Myelosuppression was significant, resulting in considerable reductions in the dose schedules. After 12 months of therapy, the median IFN-alpha dose was 1.6 MU/m(2) daily, the median ara-C dose was 1.85 mg daily, and the median number of HHT days was 2 every month. Only three patients developed blastic phase while receiving the triple regimen. With the change to imatinib therapy, currently 57 patients (63%) are in complete cytogenetic response and 69 patients (76%) in major cytogenetic response. With a median follow-up time of 46 months for the total study group, the estimated 5-year survival rate was 88%, and only 8 patients (9%) to date have developed blastic phase. CONCLUSIONS: The sequence of IFN-alpha, ara-C, and HHT followed by imatinib (imposed by the discovery of the latter drug) resulted in an estimated 5-year survival rate of 88%. This finding suggests that imatinib combination regimens may improve the prognosis in CML.

Adult↗

PubMed2003

Prediction of initial cytogenetic response for subsequent major and complete cytogenetic response to imatinib mesylate therapy in patients with Philadelphia chromosome-positive chronic myelogenous leukemia.

BACKGROUND: Obtaining a major (Philadelphia chromosome [Ph] of < 35%) or a complete cytogenetic response (Ph of 0%) has been associated with excellent long-term survival. Cytogenetic response may continue to improve with therapy. Because early allogeneic stem cell transplantation (SCT) may be associated with a better outcome, early parameters predicting for subsequent cytogenetic responses would optimize the treatment decision-making. METHODS: The current study was performed to analyze whether early cytogenetic responses may be predictive of later major or complete cytogenetic responses to imatinib mesylate therapy in patients with Ph-positive chronic myelogenous leukemia (CML). RESULTS: Two hundred sixty-one patients with Ph-positive, chronic-phase CML after failure with interferon therapy who were treated with imatinib mesylate therapy were analyzed. A persistence of 100% Ph-positive cells after > or = 6 months of imatinib mesylate therapy was associated with a major cytogenetic response rate of 9-13% and a complete cytogenetic response rate of 0-4%. However, a minor cytogenetic response after 3-12 months of therapy still was associated with high rates of major (68-83%) or complete (35-54%) cytogenetic response rates. CONCLUSIONS: Patients with Ph-positive, chronic-phase CML who have persistent 100% Ph-positive disease after > or = 6 months of imatinib mesylate therapy may be offered allogeneic SCT or considered for alternative investigational therapies.

Benzamides↗

PubMed2002

YMD: a microarray database for large-scale gene expression analysis.

The use of microarray technology to perform parallel analysis of the expression pattern of a large number of genes in a single experiment has created a new frontier of medical research. The vast amount of gene expression data generated from multiple microarray experiments requires a robust database system that allows efficient data storage, retrieval, secure access, data dissemination, and integrated data analyses. To address the growing needs of microarray researchers at Yale and their collaborators, we have built the Yale Microarray Database (YMD). YMD is Web-accessible with the following features: (i) a Web program that tracks DNA samples between source plates and arrays, (ii) the capability of finding common genes/clones across different array platforms, (iii) an image file server, (iv) laboratory-based user management and access privileges, (v) project management, (vi) template data entry, (vii) linking gene expression data to annotation databases for functional analysis. YMD is currently being used on a pilot basis by several laboratories for different organisms and array platforms.

Databases, Nucleic Acid↗

PubMedDate not supplied

A dynamic approach to mapping coordinates between microplates and microarrays.

The retrieval of useful data from spotted microarray slides requires keeping track of which microplate wells and DNA sample corresponds to each spot on each array slide. Existing approaches are closely coupled with the type of arrayer in use and are computer operating-system-specific. To support the microarray researcher community at large who use different arrayers and computer platforms, increased flexibility, generality, and portability of these approaches are required. In this paper, we describe a general algorithm that correlates the well positions of DNA samples in each microplate to the positions of the spots on each array slide. Based on this algorithm, we have implemented a flexible and platform-independent program named MicroArray Convolutor (MAC) that provides a Web solution allowing the user to: (a) import a text file that identifies the DNA samples and their well locations, (b) select a transformation method that converts data in 96-well plate format into 384-well plate format, and (c) specify the output format of the array lists dependant on the configuration of the array platform as well as the downstream analysis software chosen for the array. MAC and its source code can be accessed via the following Web address: http://ymd.med.yale.edu/kei-cgi/kc_mac_dev8.pl.

Algorithms↗