Characteristics associated with important clinical end points in patients with chronic lymphocytic leukemia at initial treatment

William G. Wierda, Susan O'Brien, Xuemei Wang, Stefan Faderl, Alessandra Ferrajoli, Kim Anh Do, Guillermo Garcia-Manero, Jorge Cortes, Deborah Thomas, Charles Koller, Jan Burger, Susan Lerner, Hagop Kantarjian, Michael Keating

Research output: Contribution to journalArticle

Abstract

Purpose Response to front-line treatment and subsequent clinical course for patients with chronic lymphocytic leukemia (CLL) are heterogeneous. Identifying pretreatment patient characteristics or prognostic factors associated with clinical outcomes is important for counseling patients, conducting clinical research, and evaluating trial results. Patients and Methods We evaluated the pretreatment characteristics of 595 previously untreated patients who had National Cancer Institute Working Group indications to initiate front-line therapy for predictors of complete response (CR), time to treatment failure (TTF), and overall survival (OS). Multivariable models were developed for all three end points. Results CR is an important treatment end point correlated with longer TTF and OS. In this retrospective analysis, front-line treatment regimen was a significant independent predictive factor for all three end points; chemoimmunotherapy was the superior treatment regimen. Considering front-line treatment regimen, other independent patient characteristics associated with CR included age and β-microglobulin (β-2M). TTF was independently associated with age, β-2M, percent lymphocytes in bone marrow, and treatment regimen. Improved OS was independently associated with younger age, lower β-2M, and treatment regimen. Two weighted prognostic models or nomograms, one including and one excluding treatment regimen, were constructed using significant characteristics to predict 5- and 10-year survival probability and estimate median survival time. Conclusion Identifying pretreatment patient characteristics associated with CR, TTF, and OS establishes a baseline to compare and incorporate new prognostic factors. Treatment had an impact on the significance of these factors. Prognostic models may help patients and clinicians in decision making as well as facilitate clinical research through design and analyses of clinical trials.

Original languageEnglish (US)
Pages (from-to)1637-1643
Number of pages7
JournalJournal of Clinical Oncology
Volume27
Issue number10
DOIs
StatePublished - Apr 1 2009
Externally publishedYes

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B-Cell Chronic Lymphocytic Leukemia
Treatment Failure
Survival
Therapeutics
Nomograms
National Cancer Institute (U.S.)
Reaction Time
Counseling
Decision Making
Research Design
Bone Marrow
Clinical Trials
Lymphocytes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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Characteristics associated with important clinical end points in patients with chronic lymphocytic leukemia at initial treatment. / Wierda, William G.; O'Brien, Susan; Wang, Xuemei; Faderl, Stefan; Ferrajoli, Alessandra; Do, Kim Anh; Garcia-Manero, Guillermo; Cortes, Jorge; Thomas, Deborah; Koller, Charles; Burger, Jan; Lerner, Susan; Kantarjian, Hagop; Keating, Michael.

In: Journal of Clinical Oncology, Vol. 27, No. 10, 01.04.2009, p. 1637-1643.

Research output: Contribution to journalArticle

Wierda, WG, O'Brien, S, Wang, X, Faderl, S, Ferrajoli, A, Do, KA, Garcia-Manero, G, Cortes, J, Thomas, D, Koller, C, Burger, J, Lerner, S, Kantarjian, H & Keating, M 2009, 'Characteristics associated with important clinical end points in patients with chronic lymphocytic leukemia at initial treatment', Journal of Clinical Oncology, vol. 27, no. 10, pp. 1637-1643. https://doi.org/10.1200/JCO.2008.18.1701
Wierda, William G. ; O'Brien, Susan ; Wang, Xuemei ; Faderl, Stefan ; Ferrajoli, Alessandra ; Do, Kim Anh ; Garcia-Manero, Guillermo ; Cortes, Jorge ; Thomas, Deborah ; Koller, Charles ; Burger, Jan ; Lerner, Susan ; Kantarjian, Hagop ; Keating, Michael. / Characteristics associated with important clinical end points in patients with chronic lymphocytic leukemia at initial treatment. In: Journal of Clinical Oncology. 2009 ; Vol. 27, No. 10. pp. 1637-1643.
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AU - Ferrajoli, Alessandra

AU - Do, Kim Anh

AU - Garcia-Manero, Guillermo

AU - Cortes, Jorge

AU - Thomas, Deborah

AU - Koller, Charles

AU - Burger, Jan

AU - Lerner, Susan

AU - Kantarjian, Hagop

AU - Keating, Michael

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N2 - Purpose Response to front-line treatment and subsequent clinical course for patients with chronic lymphocytic leukemia (CLL) are heterogeneous. Identifying pretreatment patient characteristics or prognostic factors associated with clinical outcomes is important for counseling patients, conducting clinical research, and evaluating trial results. Patients and Methods We evaluated the pretreatment characteristics of 595 previously untreated patients who had National Cancer Institute Working Group indications to initiate front-line therapy for predictors of complete response (CR), time to treatment failure (TTF), and overall survival (OS). Multivariable models were developed for all three end points. Results CR is an important treatment end point correlated with longer TTF and OS. In this retrospective analysis, front-line treatment regimen was a significant independent predictive factor for all three end points; chemoimmunotherapy was the superior treatment regimen. Considering front-line treatment regimen, other independent patient characteristics associated with CR included age and β-microglobulin (β-2M). TTF was independently associated with age, β-2M, percent lymphocytes in bone marrow, and treatment regimen. Improved OS was independently associated with younger age, lower β-2M, and treatment regimen. Two weighted prognostic models or nomograms, one including and one excluding treatment regimen, were constructed using significant characteristics to predict 5- and 10-year survival probability and estimate median survival time. Conclusion Identifying pretreatment patient characteristics associated with CR, TTF, and OS establishes a baseline to compare and incorporate new prognostic factors. Treatment had an impact on the significance of these factors. Prognostic models may help patients and clinicians in decision making as well as facilitate clinical research through design and analyses of clinical trials.

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