Cytogenetic prioritization with inclusion of molecular markers predicts outcome in previously untreated patients with chronic lymphocytic leukemia treated with fludarabine or fludarabine plus cyclophosphamide: A long-term follow-up study of the US intergroup phase III trial E2997

David M. Lucas, Amy S. Ruppert, Gerard Lozanski, Gordon W. Dewald, Arletta Lozanski, Rainer Claus, Christoph Plass, Ian W. Flinn, Donna S. Neuberg, Elisabeth M. Paietta, John M. Bennett, Diane F. Jelinek, John G. Gribben, Mohamad A. Hussein, Frederick R. Appelbaum, Richard A. Larson, Dennis F. Moore, Martin S. Tallman, John C. Byrd, Michael R. Grever

Research output: Contribution to journalArticle

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Abstract

Fludarabine (F) and cyclophosphamide (C) remain backbones of up-front chemotherapy regimens for chronic lymphocytic leukemia (CLL). We report long-term follow-up of a randomized F vs. FC trial in untreated CLL#. With median follow-up of 88 months, estimated median progression-free survival (PFS) was 19.3 vs. 48.1 months for F (n = 109) and FC (n = 118), respectively (p <0.0001), and median overall survival (OS) was 88.0 vs. 79.1 months (p = 0.96). In multivariable analyses, variables associated with inferior PFS and OS respectively were age (p = 0.002, p <0.001), Rai stage (p = 0.006, p = 0.02) and sex (p = 0.03, PFS only). Del(17)(p13.1) predicted shorter PFS and OS (p <0.0001 for each), as did del(11q)(22.3) (p <0.0001, p = 0.005, respectively), trisomy 12 with mutated Notch1 (p = 0.003, p = 0.03, respectively) and unmutated IGHV (p = 0.009, p = 0.002, respectively), all relative to patients without these features. These data confirm results from shorter follow-up and further justify targeted therapies for CLL.

Original languageEnglish (US)
Pages (from-to)3031-3037
Number of pages7
JournalLeukemia and Lymphoma
Volume56
Issue number11
DOIs
StatePublished - Nov 2 2015

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B-Cell Chronic Lymphocytic Leukemia
Cytogenetics
Cyclophosphamide
Disease-Free Survival
Survival
Trisomy
Drug Therapy
fludarabine
Therapeutics

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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Cytogenetic prioritization with inclusion of molecular markers predicts outcome in previously untreated patients with chronic lymphocytic leukemia treated with fludarabine or fludarabine plus cyclophosphamide : A long-term follow-up study of the US intergroup phase III trial E2997. / Lucas, David M.; Ruppert, Amy S.; Lozanski, Gerard; Dewald, Gordon W.; Lozanski, Arletta; Claus, Rainer; Plass, Christoph; Flinn, Ian W.; Neuberg, Donna S.; Paietta, Elisabeth M.; Bennett, John M.; Jelinek, Diane F.; Gribben, John G.; Hussein, Mohamad A.; Appelbaum, Frederick R.; Larson, Richard A.; Moore, Dennis F.; Tallman, Martin S.; Byrd, John C.; Grever, Michael R.

In: Leukemia and Lymphoma, Vol. 56, No. 11, 02.11.2015, p. 3031-3037.

Research output: Contribution to journalArticle

Lucas, DM, Ruppert, AS, Lozanski, G, Dewald, GW, Lozanski, A, Claus, R, Plass, C, Flinn, IW, Neuberg, DS, Paietta, EM, Bennett, JM, Jelinek, DF, Gribben, JG, Hussein, MA, Appelbaum, FR, Larson, RA, Moore, DF, Tallman, MS, Byrd, JC & Grever, MR 2015, 'Cytogenetic prioritization with inclusion of molecular markers predicts outcome in previously untreated patients with chronic lymphocytic leukemia treated with fludarabine or fludarabine plus cyclophosphamide: A long-term follow-up study of the US intergroup phase III trial E2997', Leukemia and Lymphoma, vol. 56, no. 11, pp. 3031-3037. https://doi.org/10.3109/10428194.2015.1023800
Lucas, David M. ; Ruppert, Amy S. ; Lozanski, Gerard ; Dewald, Gordon W. ; Lozanski, Arletta ; Claus, Rainer ; Plass, Christoph ; Flinn, Ian W. ; Neuberg, Donna S. ; Paietta, Elisabeth M. ; Bennett, John M. ; Jelinek, Diane F. ; Gribben, John G. ; Hussein, Mohamad A. ; Appelbaum, Frederick R. ; Larson, Richard A. ; Moore, Dennis F. ; Tallman, Martin S. ; Byrd, John C. ; Grever, Michael R. / Cytogenetic prioritization with inclusion of molecular markers predicts outcome in previously untreated patients with chronic lymphocytic leukemia treated with fludarabine or fludarabine plus cyclophosphamide : A long-term follow-up study of the US intergroup phase III trial E2997. In: Leukemia and Lymphoma. 2015 ; Vol. 56, No. 11. pp. 3031-3037.
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abstract = "Fludarabine (F) and cyclophosphamide (C) remain backbones of up-front chemotherapy regimens for chronic lymphocytic leukemia (CLL). We report long-term follow-up of a randomized F vs. FC trial in untreated CLL#. With median follow-up of 88 months, estimated median progression-free survival (PFS) was 19.3 vs. 48.1 months for F (n = 109) and FC (n = 118), respectively (p <0.0001), and median overall survival (OS) was 88.0 vs. 79.1 months (p = 0.96). In multivariable analyses, variables associated with inferior PFS and OS respectively were age (p = 0.002, p <0.001), Rai stage (p = 0.006, p = 0.02) and sex (p = 0.03, PFS only). Del(17)(p13.1) predicted shorter PFS and OS (p <0.0001 for each), as did del(11q)(22.3) (p <0.0001, p = 0.005, respectively), trisomy 12 with mutated Notch1 (p = 0.003, p = 0.03, respectively) and unmutated IGHV (p = 0.009, p = 0.002, respectively), all relative to patients without these features. These data confirm results from shorter follow-up and further justify targeted therapies for CLL.",
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AU - Lucas, David M.

AU - Ruppert, Amy S.

AU - Lozanski, Gerard

AU - Dewald, Gordon W.

AU - Lozanski, Arletta

AU - Claus, Rainer

AU - Plass, Christoph

AU - Flinn, Ian W.

AU - Neuberg, Donna S.

AU - Paietta, Elisabeth M.

AU - Bennett, John M.

AU - Jelinek, Diane F.

AU - Gribben, John G.

AU - Hussein, Mohamad A.

AU - Appelbaum, Frederick R.

AU - Larson, Richard A.

AU - Moore, Dennis F.

AU - Tallman, Martin S.

AU - Byrd, John C.

AU - Grever, Michael R.

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