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Dive into the research topics where A. Thomas Look is active.

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NCI monographs : a publication of the National Cancer Institute | 2009

Clinical pharmacodynamic studies of high-dose methotrexate in acute lymphocytic leukemia

William E. Evans; William R. Crom; Minnie Abromowitch; Richard K. Dodge; A. Thomas Look; W. Paul Bowman; Stephen L. George; Ching-Hon Pui

High-dose methotrexate (500 to 33,600 mg per square meter of body-surface area) with leucovorin rescue is a common component of therapy for acute lymphocytic leukemia. To increase understanding of the relation between the serum concentration and the effect of methotrexate, we conducted a randomized, prospective study of 108 children with standard-risk acute lymphocytic leukemia who were treated with 15 doses of methotrexate (1000 mg per square meter) that were infused over 24 hours. The median length of follow-up was 3.5 years from diagnosis for patients still in remission. Variability between patients in methotrexate clearance produced steady-state serum concentrations that ranged from 9.3 to 25.4 microM. Patients with median methotrexate concentrations of less than 16 microM (n = 59) had a lower probability of remaining in remission (P less than 0.05) than patients with concentrations of 16 microM or more (n = 49). Multivariate analyses indicated that patients with methotrexate concentrations of less than 16 microM were 3 times more likely to have any kind of relapse during therapy (P = 0.01) and 7 times more likely to have a hematologic relapse during therapy (P = 0.001). Stepwise Coxs regression identified leukemic-cell DNA content, methotrexate concentration, and hemoglobin as significant prognostic variables for hematologic relapse (P = 0.0005). We conclude that there is a concentration-effect relation for high-dose methotrexate in acute lymphocytic leukemia and that 1000 mg per square meter infused over a period of 24 hours may not be optimal for patients with relatively fast drug clearance.As the intensity of cancer chemotherapy has been reported to influence clinical response for several drug-sensitive cancers, we have investigated the relation between systemic exposure to high-dose methotrexate (HDMTX) and clinical response in childhood acute lymphocytic leukemia (ALL). A total of 108 consecutive, previously untreated children with standard-intermediate risk ALL were randomized to receive postinduction therapy with HDMTX (1000 mg/m2 iv over 24 hours weekly for 3 weeks, then every 6 weeks for 72 weeks), superimposed on conventional therapy with low-dose 6-mercaptopurine (6MP; 50 mg/m2 orally per day) and methotrexate (MTX; 25 mg/m2 orally per week). The systemic clearance of HDMTX ranged from 40 to 131 ml/minute/m2 among these patients, yielding MTX steady-state plasma concentrations (Cpss) ranging from 9.3 to 25.4 microM during the infusion. The group of patients (n = 59) with median MTX Cpss less than 16 microM during the HDMTX infusion had a higher probability of having any relapse than patients (n = 49) with MTX Cpss greater than 16 microM (P less than 0.05). In a previously reported univariate analysis, patients with MTX Cpss less than or equal to 16 microM were 3.2 times more likely to relapse on therapy (P = 0.01) and 6.9 times more likely to have a hematologic relapse on therapy (P = 0.001). Multivariate and stepwise Coxs regression analyses indicated that MTX Cpss retains its prognostic importance even when other prognostic variables (i.e., DNA Index, WBC, hemoglobin) are considered.(ABSTRACT TRUNCATED AT 250 WORDS)


Cell | 1988

Tandem linkage of human CSF-1 receptor (c-fms) and PDGF receptor genes

W.Mark Roberts; A. Thomas Look; Martine F. Roussel; Charles J. Sherr

A 5 untranslated exon of the human CSF-1 receptor gene (c-fms) is separated by a 26 kb intron from the 32 kb receptor coding sequences. Nucleotide sequence analysis of cloned genomic DNA revealed that the 3 end of the PDGF receptor gene is located less than 0.5 kb upstream from this exon. Similarities in chromosomal localization, organization, and encoded amino acid sequences suggest that the genes encoding the CSF-1 and PDGF receptors arose through duplication. The as yet unidentified c-fms promoter/enhancer sequences may be confined to the nucleotides separating the two genes or could potentially lie within the PDGF receptor gene itself.


Leukemia Research | 1986

Unfavorable presenting clinical and laboratory features are associated with calla-negative non-t, non-b lymphoblastic leukemia in children

Ching-Hon Pui; Dorothy L. Williams; Susana C. Raimondi; Susan L. Melvin; Frederick G. Behm; A. Thomas Look; Gary V. Dahl; Gaston K. Rivera; David K. Kalwinsky; Joseph Mirro; Richard K. Dodge; Sharon B. Murphy

Twenty-four (5.7%) of 424 children with newly diagnosed acute lymphoblastic leukemia (ALL) were found to have blast cells that expressed HLA-DR antigens but not the common ALL antigen (CALLA), E-rosette receptors, T-cell antigens, or cytoplasmic or surface immunoglobulins. Each of the eight cases tested expressed the B-cell associated antigen B4, but not B1 or B2 antigen. Myeloid-associated antigens were not present in any of the 10 cases tested. By comparison with common (CALLA+ B-cell precursor) ALL, patients having this immunophenotype were more likely to be children less than 2 yr of age (p less than 0.001), to have higher initial leukocyte counts (p less than 0.001), and to have blast cells with a DNA index less than 1.16 (p = 0.05), a pseudodiploid karyotype (p = 0.01) and a chromosomal translocation (p = 0.003). The presence of any chromosomal translocation in these CALLA- ALL was related to measures of increased leukemic cell burden including higher leukocyte counts, larger liver and spleen sizes and higher serum lactic dehydrogenase levels. While the patients were entered into several treatment arms of two protocols, the CALLA- cases appeared to have lower remission rate (p = 0.06) and shorter event-free survival time (p = 0.05) than did those with common ALL. The association with clinical and laboratory features of known adverse prognostic significance provides some explanation for the poor treatment outcome of CALLA- ALL.


Cancer | 1993

Correlation between Morphologic and Other Prognostic Markers of Neuroblastoma A Study of Histologic Grade, DNA Index, N-myc Gene Copy Number, and Lactic Dehydrogenase in Patients in the Pediatric Oncology Group

Vijay V. Joshi; Ernest W. Larkin; C. Tate Holbrook; Jan F. Silverman; H. Thomas Norris; Alan B. Cantor; Jonathan J. Shuster; Garrett M. Brodeur; A. Thomas Look; F. Ann Hayes; Geoffrey Altshuler; E. Ide Smith; Robert P. Castleberry

Background. Histologic grades (HG), N‐myc (NM) gene copy number, DNA index (DI), and serum lactic dehydrogenase (LDH) have been shown to be related to prognosis in neuroblastoma. The relationship between HG and nonmorphologic prognostic markers has not been investigated previously.


Science | 1997

Oncogenic transcription factors in the human acute leukemias

A. Thomas Look


Medical and Pediatric Oncology | 1988

High‐dose methotrexate improves clinical outcome in children with acute lymphoblastic leukemia: St. Jude total therapy study X

Minnie Abromowitch; Judith Ochs; Ching-Hon Pui; David K. Kalwinsky; Gaston K. Rivera; Diane L. Fairclough; A. Thomas Look; H. Omar Hustu; Sharon B. Murphy; William E. Evans; Gary V. Dahl; W. Paul Bowman


Cancer Research Therapy and Control | 1999

Identification of newly diagnosed children with acute lymphocytic leukemia at high risk for relapse

Jonathan J. Shuster; Bruch M. Camitta; Jeanette Pullen; Michael J. Borowitz; Andrew J. Carroll; A. Thomas Look; Donald H. Mahoney; Hazem Mahmoud; Stephen J. Lauer; Vita J. Land


Genes, Chromosomes and Cancer | 1992

Subiocalization of the chromosome 5 breakpoint of the 3;5 translocation in myelodysplastic syndromes and acute myeloid leukemia

Stephan W. Morris; John T. Foust; Marcus B. Valentine; W.Mark Roberts; David N. Shapiro; A. Thomas Look


The Japanese Journal of Pediatric Hematology | 1993

Clinical and Biological Implications of Chromosomal Translocations and Ploidy in Childhood Acute Lymphoblastic Leukemia.

A. Thomas Look


Archive | 2011

Frequent Deletion of p16*NK4a/MTSl and in Pediatric Acute Lymphoblastic Leukemia

Tsukasa Okuda; Sheila A. Shurtleff; Marcus B. Valentine; Susana C. Raimondi; David R. Head; Frederick G. Behm; Anita M. Curcio-Brint; Qing Liu; Ching-Hon Pui; Charles J. Sherr; David Beach; A. Thomas Look; James R. Downing

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Charles J. Sherr

Cold Spring Harbor Laboratory

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David K. Kalwinsky

St. Jude Children's Research Hospital

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Frederick G. Behm

St. Jude Children's Research Hospital

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Gaston K. Rivera

University of Tennessee Health Science Center

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Marcus B. Valentine

St. Jude Children's Research Hospital

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Minnie Abromowitch

St. Jude Children's Research Hospital

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