Abstract | PURPOSE: PATIENTS AND METHODS: We prospectively evaluated the prognostic significance of a comprehensive panel of laboratory factors on both response and progression-free survival (PFS) using samples and data from 235 patients enrolled onto a therapeutic trial. Patients received either fludarabine (FL; n = 113) or fludarabine plus cyclophosphamide (FC; n = 122) as part of a US Intergroup randomized trial for previously untreated CLL patients. RESULTS: Complete response (CR) rates were 24.6% for patients receiving FC and 5.3% for patients receiving FL (P = .00004). PFS was statistically significantly longer in patients receiving FC (median, 33.5 months for patients receiving FC and 19.9 months for patients receiving FL; P < .0001). The occurrence of del(17p13.1) (hazard ratio, 3.428; P = .0002) or del(11q22.3) (hazard ratio, 1.904; P = .006) was associated with reduced PFS. CR and overall response rates were not significantly different based on cytogenetics, IgVH mutational status, CD38 expression, or p53 mutational status. Expression of ZAP-70, Bcl-2, Bax, Mcl-1, XIAP, Caspase-3, and Traf-1 was not associated with either clinical response or PFS. CONCLUSION: These results support the use of interphase cytogenetic analysis, but not IgVH, CD38 expression, or ZAP-70 status, to predict outcome of FL-based chemotherapy. Patients with high-risk cytogenetic features should be considered for alternative therapies.
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Authors | Michael R Grever, David M Lucas, Gordon W Dewald, Donna S Neuberg, John C Reed, Shinichi Kitada, Ian W Flinn, Martin S Tallman, Frederick R Appelbaum, Richard A Larson, Elisabeth Paietta, Diane F Jelinek, John G Gribben, John C Byrd |
Journal | Journal of clinical oncology : official journal of the American Society of Clinical Oncology
(J Clin Oncol)
Vol. 25
Issue 7
Pg. 799-804
(Mar 01 2007)
ISSN: 1527-7755 [Electronic] United States |
PMID | 17283363
(Publication Type: Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural)
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Chemical References |
- Immunoglobulin Heavy Chains
- Immunoglobulin Variable Region
- ZAP-70 Protein-Tyrosine Kinase
- ADP-ribosyl Cyclase 1
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Topics |
- ADP-ribosyl Cyclase 1
(analysis)
- Adult
- Aged
- Aged, 80 and over
- Apoptosis
- Chromosome Aberrations
- Female
- Genes, p53
- Humans
- Immunoglobulin Heavy Chains
(genetics)
- Immunoglobulin Variable Region
(genetics)
- Leukemia, Lymphocytic, Chronic, B-Cell
(drug therapy, genetics, mortality)
- Male
- Middle Aged
- Mutation
- Prospective Studies
- ZAP-70 Protein-Tyrosine Kinase
(analysis)
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