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Comprehensive Assessment of Genetic and Molecular Features Predicting Outcome in Patients With Chronic Lymphocytic Leukemia: Results From the US Intergroup Phase III Trial E2997
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| Zeitschriftentitel: | Journal of Clinical Oncology |
|---|---|
| Personen und Körperschaften: | , , , , , , , , , , , , , |
| In: | Journal of Clinical Oncology, 25, 2007, 7, S. 799-804 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
American Society of Clinical Oncology (ASCO)
|
| Schlagwörter: |
| author_facet |
Grever, Michael R. Lucas, David M. Dewald, Gordon W. Neuberg, Donna S. Reed, John C. Kitada, Shinichi Flinn, Ian W. Tallman, Martin S. Appelbaum, Frederick R. Larson, Richard A. Paietta, Elisabeth Jelinek, Diane F. Gribben, John G. Byrd, John C. Grever, Michael R. Lucas, David M. Dewald, Gordon W. Neuberg, Donna S. Reed, John C. Kitada, Shinichi Flinn, Ian W. Tallman, Martin S. Appelbaum, Frederick R. Larson, Richard A. Paietta, Elisabeth Jelinek, Diane F. Gribben, John G. Byrd, John C. |
|---|---|
| author |
Grever, Michael R. Lucas, David M. Dewald, Gordon W. Neuberg, Donna S. Reed, John C. Kitada, Shinichi Flinn, Ian W. Tallman, Martin S. Appelbaum, Frederick R. Larson, Richard A. Paietta, Elisabeth Jelinek, Diane F. Gribben, John G. Byrd, John C. |
| spellingShingle |
Grever, Michael R. Lucas, David M. Dewald, Gordon W. Neuberg, Donna S. Reed, John C. Kitada, Shinichi Flinn, Ian W. Tallman, Martin S. Appelbaum, Frederick R. Larson, Richard A. Paietta, Elisabeth Jelinek, Diane F. Gribben, John G. Byrd, John C. Journal of Clinical Oncology Comprehensive Assessment of Genetic and Molecular Features Predicting Outcome in Patients With Chronic Lymphocytic Leukemia: Results From the US Intergroup Phase III Trial E2997 Cancer Research Oncology |
| author_sort |
grever, michael r. |
| spelling |
Grever, Michael R. Lucas, David M. Dewald, Gordon W. Neuberg, Donna S. Reed, John C. Kitada, Shinichi Flinn, Ian W. Tallman, Martin S. Appelbaum, Frederick R. Larson, Richard A. Paietta, Elisabeth Jelinek, Diane F. Gribben, John G. Byrd, John C. 0732-183X 1527-7755 American Society of Clinical Oncology (ASCO) Cancer Research Oncology http://dx.doi.org/10.1200/jco.2006.08.3089 <jats:sec><jats:title>Purpose</jats:title><jats:p> Genomic features including unmutated immunoglobulin variable region heavy chain (IgV<jats:sub>H</jats:sub>) genes, del(11q22.3), del(17p13.1), and p53 mutations have been reported to predict the clinical course and overall survival of patients with chronic lymphocytic leukemia (CLL). In addition, ZAP-70 and Bcl-2 family proteins have been explored as predictors of outcome. </jats:p></jats:sec><jats:sec><jats:title>Patients and Methods</jats:title><jats:p> 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. </jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p> 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, IgV<jats:sub>H</jats:sub> 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. </jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p> These results support the use of interphase cytogenetic analysis, but not IgV<jats:sub>H</jats:sub>, 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. </jats:p></jats:sec> Comprehensive Assessment of Genetic and Molecular Features Predicting Outcome in Patients With Chronic Lymphocytic Leukemia: Results From the US Intergroup Phase III Trial E2997 Journal of Clinical Oncology |
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| title |
Comprehensive Assessment of Genetic and Molecular Features Predicting Outcome in Patients With Chronic Lymphocytic Leukemia: Results From the US Intergroup Phase III Trial E2997 |
| title_unstemmed |
Comprehensive Assessment of Genetic and Molecular Features Predicting Outcome in Patients With Chronic Lymphocytic Leukemia: Results From the US Intergroup Phase III Trial E2997 |
| title_full |
Comprehensive Assessment of Genetic and Molecular Features Predicting Outcome in Patients With Chronic Lymphocytic Leukemia: Results From the US Intergroup Phase III Trial E2997 |
| title_fullStr |
Comprehensive Assessment of Genetic and Molecular Features Predicting Outcome in Patients With Chronic Lymphocytic Leukemia: Results From the US Intergroup Phase III Trial E2997 |
| title_full_unstemmed |
Comprehensive Assessment of Genetic and Molecular Features Predicting Outcome in Patients With Chronic Lymphocytic Leukemia: Results From the US Intergroup Phase III Trial E2997 |
| title_short |
Comprehensive Assessment of Genetic and Molecular Features Predicting Outcome in Patients With Chronic Lymphocytic Leukemia: Results From the US Intergroup Phase III Trial E2997 |
| title_sort |
comprehensive assessment of genetic and molecular features predicting outcome in patients with chronic lymphocytic leukemia: results from the us intergroup phase iii trial e2997 |
| topic |
Cancer Research Oncology |
| url |
http://dx.doi.org/10.1200/jco.2006.08.3089 |
| publishDate |
2007 |
| physical |
799-804 |
| description |
<jats:sec><jats:title>Purpose</jats:title><jats:p> Genomic features including unmutated immunoglobulin variable region heavy chain (IgV<jats:sub>H</jats:sub>) genes, del(11q22.3), del(17p13.1), and p53 mutations have been reported to predict the clinical course and overall survival of patients with chronic lymphocytic leukemia (CLL). In addition, ZAP-70 and Bcl-2 family proteins have been explored as predictors of outcome. </jats:p></jats:sec><jats:sec><jats:title>Patients and Methods</jats:title><jats:p> 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. </jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p> 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, IgV<jats:sub>H</jats:sub> 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. </jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p> These results support the use of interphase cytogenetic analysis, but not IgV<jats:sub>H</jats:sub>, 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. </jats:p></jats:sec> |
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| author | Grever, Michael R., Lucas, David M., Dewald, Gordon W., Neuberg, Donna S., Reed, John C., Kitada, Shinichi, Flinn, Ian W., Tallman, Martin S., Appelbaum, Frederick R., Larson, Richard A., Paietta, Elisabeth, Jelinek, Diane F., Gribben, John G., Byrd, John C. |
| author_facet | Grever, Michael R., Lucas, David M., Dewald, Gordon W., Neuberg, Donna S., Reed, John C., Kitada, Shinichi, Flinn, Ian W., Tallman, Martin S., Appelbaum, Frederick R., Larson, Richard A., Paietta, Elisabeth, Jelinek, Diane F., Gribben, John G., Byrd, John C., Grever, Michael R., Lucas, David M., Dewald, Gordon W., Neuberg, Donna S., Reed, John C., Kitada, Shinichi, Flinn, Ian W., Tallman, Martin S., Appelbaum, Frederick R., Larson, Richard A., Paietta, Elisabeth, Jelinek, Diane F., Gribben, John G., Byrd, John C. |
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| description | <jats:sec><jats:title>Purpose</jats:title><jats:p> Genomic features including unmutated immunoglobulin variable region heavy chain (IgV<jats:sub>H</jats:sub>) genes, del(11q22.3), del(17p13.1), and p53 mutations have been reported to predict the clinical course and overall survival of patients with chronic lymphocytic leukemia (CLL). In addition, ZAP-70 and Bcl-2 family proteins have been explored as predictors of outcome. </jats:p></jats:sec><jats:sec><jats:title>Patients and Methods</jats:title><jats:p> 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. </jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p> 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, IgV<jats:sub>H</jats:sub> 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. </jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p> These results support the use of interphase cytogenetic analysis, but not IgV<jats:sub>H</jats:sub>, 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. </jats:p></jats:sec> |
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| spelling | Grever, Michael R. Lucas, David M. Dewald, Gordon W. Neuberg, Donna S. Reed, John C. Kitada, Shinichi Flinn, Ian W. Tallman, Martin S. Appelbaum, Frederick R. Larson, Richard A. Paietta, Elisabeth Jelinek, Diane F. Gribben, John G. Byrd, John C. 0732-183X 1527-7755 American Society of Clinical Oncology (ASCO) Cancer Research Oncology http://dx.doi.org/10.1200/jco.2006.08.3089 <jats:sec><jats:title>Purpose</jats:title><jats:p> Genomic features including unmutated immunoglobulin variable region heavy chain (IgV<jats:sub>H</jats:sub>) genes, del(11q22.3), del(17p13.1), and p53 mutations have been reported to predict the clinical course and overall survival of patients with chronic lymphocytic leukemia (CLL). In addition, ZAP-70 and Bcl-2 family proteins have been explored as predictors of outcome. </jats:p></jats:sec><jats:sec><jats:title>Patients and Methods</jats:title><jats:p> 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. </jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p> 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, IgV<jats:sub>H</jats:sub> 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. </jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p> These results support the use of interphase cytogenetic analysis, but not IgV<jats:sub>H</jats:sub>, 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. </jats:p></jats:sec> Comprehensive Assessment of Genetic and Molecular Features Predicting Outcome in Patients With Chronic Lymphocytic Leukemia: Results From the US Intergroup Phase III Trial E2997 Journal of Clinical Oncology |
| spellingShingle | Grever, Michael R., Lucas, David M., Dewald, Gordon W., Neuberg, Donna S., Reed, John C., Kitada, Shinichi, Flinn, Ian W., Tallman, Martin S., Appelbaum, Frederick R., Larson, Richard A., Paietta, Elisabeth, Jelinek, Diane F., Gribben, John G., Byrd, John C., Journal of Clinical Oncology, Comprehensive Assessment of Genetic and Molecular Features Predicting Outcome in Patients With Chronic Lymphocytic Leukemia: Results From the US Intergroup Phase III Trial E2997, Cancer Research, Oncology |
| title | Comprehensive Assessment of Genetic and Molecular Features Predicting Outcome in Patients With Chronic Lymphocytic Leukemia: Results From the US Intergroup Phase III Trial E2997 |
| title_full | Comprehensive Assessment of Genetic and Molecular Features Predicting Outcome in Patients With Chronic Lymphocytic Leukemia: Results From the US Intergroup Phase III Trial E2997 |
| title_fullStr | Comprehensive Assessment of Genetic and Molecular Features Predicting Outcome in Patients With Chronic Lymphocytic Leukemia: Results From the US Intergroup Phase III Trial E2997 |
| title_full_unstemmed | Comprehensive Assessment of Genetic and Molecular Features Predicting Outcome in Patients With Chronic Lymphocytic Leukemia: Results From the US Intergroup Phase III Trial E2997 |
| title_short | Comprehensive Assessment of Genetic and Molecular Features Predicting Outcome in Patients With Chronic Lymphocytic Leukemia: Results From the US Intergroup Phase III Trial E2997 |
| title_sort | comprehensive assessment of genetic and molecular features predicting outcome in patients with chronic lymphocytic leukemia: results from the us intergroup phase iii trial e2997 |
| title_unstemmed | Comprehensive Assessment of Genetic and Molecular Features Predicting Outcome in Patients With Chronic Lymphocytic Leukemia: Results From the US Intergroup Phase III Trial E2997 |
| topic | Cancer Research, Oncology |
| url | http://dx.doi.org/10.1200/jco.2006.08.3089 |