Advertisement
Journal of Clinical Oncology  
Search for:
Limit by:
  Browse by Subject or Issue
Home Search or Browse JCO My JCO Subscriptions Customer Service Site Map

Originally published as JCO Early Release 10.1200/JCO.2005.03.1021 on December 12 2005

Journal of Clinical Oncology, Vol 24, No 3 (January 20), 2006: pp. 437-443
© 2006 American Society of Clinical Oncology.
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a colleague
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Save to my personal folders
Right arrow Download to citation manager
Right arrowRights & Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Byrd, J. C.
Right arrow Articles by Heerema, N. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Byrd, J. C.
Right arrow Articles by Heerema, N. A.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Facebook   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?

Select High-Risk Genetic Features Predict Earlier Progression Following Chemoimmunotherapy With Fludarabine and Rituximab in Chronic Lymphocytic Leukemia: Justification for Risk-Adapted Therapy

John C. Byrd, John G. Gribben, Bercedis L. Peterson, Michael R. Grever, Gerard Lozanski, David M. Lucas, Ben Lampson, Richard A. Larson, Michael A. Caligiuri, Nyla A. Heerema

From the Division of Hematology-Oncology, Departments of Internal Medicine and Pathology, The Ohio State University, Columbus, OH; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA; CALGB Statistical Center, Durham, NC; Department of Medicine, The University of Chicago, Chicago, IL

Address reprint requests to John C. Byrd, MD, Division of Hematology-Oncology, Starling Loving Hall, Room 302, The Ohio State University, Columbus, OH 43210; john.byrd{at}osumc.edu

Purpose Several new prognostic factors predicting rapid disease progression in chronic lymphocytic leukemia (CLL) have been identified, including unmutated Ig VH mutational status, del(11)(q23), del(17)(p13.1), and p53 mutations. To date, the impact of these same prognostic factors have not been examined relative to treatment outcome with chemoimmunotherapy.

Methods We examined the impact of these new prognostic factors on predicting treatment outcome in symptomatic, untreated CLL patients who received chemoimmunotherapy with fludarabine and rituximab as part of a completed, randomized phase II study, Cancer and Leukemia Group B (CALGB) 9712.

Results Eighty-eight patients treated as part of CALGB 9712 had detailed prognostic factor assessment performed. Using Ig VH mutational status to classify risk, there was no association between complete response rate with either unmutated Ig VH mutational status or high-risk interphase cytogenetics. However, the median progression-free survival (PFS; P = .048) and overall survival (OS; P = .01) were shorter among the Ig VH unmutated patients as compared with the Ig VH mutated patients. Using the hierarchical classification of Döhner, PFS (P = .005) and OS (P = .004) were significantly longer as the classification moved from high risk [del (11)(q22.3) or del (17)(p13.1)] to low risk.

Conclusion These data demonstrate that high-risk CLL patients characterized by Ig VH unmutated (≥ 98%) or high-risk interphase cytogenetics, including either del(17p) or del(11q), appear to have a shorter PFS and OS with chemoimmunotherapy. Larger prospective studies will be required to determine the independent influence of Ig VH mutational status and interphase cytogenetics on treatment outcome.

Supported in part by grants from the National Cancer Institute (CA31946) to the Cancer and Leukemia Group B (Richard L. Schilsky, MD, Chairman), R21CA101332, and UO1CA101140. Support from the Leukemia and Lymphoma Society of America (J.C.B.), and D. Warren Brown Foundation (J.C.B.).

J.C.B. is a clinical scholar of the Leukemia and Lymphoma Society of America.

The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute.

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Facebook Facebook   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?


This article has been cited by other articles:


Home page
 Clin. Cancer Res.Home page
D. R. Friedman, J. B. Weinberg, W. T. Barry, B. K. Goodman, A. D. Volkheimer, K. M. Bond, Y. Chen, N. Jiang, J. O. Moore, J. P. Gockerman, et al.
A Genomic Approach to Improve Prognosis and Predict Therapeutic Response in Chronic Lymphocytic Leukemia
Clin. Cancer Res., November 15, 2009; 15(22): 6947 - 6955.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
S. O'Brien, J. O. Moore, T. E. Boyd, L. M. Larratt, A. B. Skotnicki, B. Koziner, A. A. Chanan-Khan, J. F. Seymour, J. Gribben, L. M. Itri, et al.
5-Year Survival in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia in a Randomized, Phase III Trial of Fludarabine Plus Cyclophosphamide With or Without Oblimersen
J. Clin. Oncol., November 1, 2009; 27(31): 5208 - 5212.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
F. Bosch, P. Abrisqueta, N. Villamor, M. J. Terol, E. Gonzalez-Barca, C. Ferra, M. Gonzalez Diaz, E. Abella, J. Delgado, F. Carbonell, et al.
Rituximab, Fludarabine, Cyclophosphamide, and Mitoxantrone: A New, Highly Active Chemoimmunotherapy Regimen for Chronic Lymphocytic Leukemia
J. Clin. Oncol., September 20, 2009; 27(27): 4578 - 4584.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
C.-Y. Tsai, A. S. Ray, D. B. Tumas, M. J. Keating, H. Reiser, and W. Plunkett
Targeting DNA Repair in Chronic Lymphocytic Leukemia Cells with a Novel Acyclic Nucleotide Analogue, GS-9219
Clin. Cancer Res., June 1, 2009; 15(11): 3760 - 3769.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
K. A. Foon, M. Boyiadzis, S. R. Land, S. Marks, A. Raptis, L. Pietragallo, D. Meisner, A. Laman, M. Sulecki, A. Butchko, et al.
Chemoimmunotherapy With Low-Dose Fludarabine and Cyclophosphamide and High Dose Rituximab in Previously Untreated Patients With Chronic Lymphocytic Leukemia
J. Clin. Oncol., February 1, 2009; 27(4): 498 - 503.
[Abstract] [Full Text] [PDF]

Home page
 Anticancer ResHome page
J. BOELENS, S. LUST, B. VANHOECKE, and F. OFFNER
Chronic Lymphocytic Leukaemia
Anticancer Res, February 1, 2009; 29(2): 605 - 615.
[Abstract] [Full Text] [PDF]

Home page
 Am Soc Clin Oncol Ed BookHome page
T. J. Kipps
Chronic Lymphocytic Leukemia: Advances in Assessing Prognosis and Therapy
ASCO Educational Book, January 1, 2009; 2009(1): 385 - 393.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
M. L. Sorror, B. E. Storer, B. M. Sandmaier, M. Maris, J. Shizuru, R. Maziarz, E. Agura, T. R. Chauncey, M. A. Pulsipher, P. A. McSweeney, et al.
Five-Year Follow-Up of Patients With Advanced Chronic Lymphocytic Leukemia Treated With Allogeneic Hematopoietic Cell Transplantation After Nonmyeloablative Conditioning
J. Clin. Oncol., October 20, 2008; 26(30): 4912 - 4920.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
D. O'Shea, C. O'Riain, C. Taylor, R. Waters, E. Carlotti, F. MacDougall, J. Gribben, A. Rosenwald, G. Ott, L. M. Rimsza, et al.
The presence of TP53 mutation at diagnosis of follicular lymphoma identifies a high-risk group of patients with shortened time to disease progression and poorer overall survival
Blood, October 15, 2008; 112(8): 3126 - 3129.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
T. Zenz, A. Krober, K. Scherer, S. Habe, A. Buhler, A. Benner, T. Denzel, D. Winkler, J. Edelmann, C. Schwanen, et al.
Monoallelic TP53 inactivation is associated with poor prognosis in chronic lymphocytic leukemia: results from a detailed genetic characterization with long-term follow-up
Blood, October 15, 2008; 112(8): 3322 - 3329.
[Abstract] [Full Text] [PDF]

Home page
 JNCI J Natl Cancer InstHome page
C. Herbst, I. Monsef, N. Skoetz, and A. Engert
Eighth Biannual Report of the Cochrane Haematological Malignancies Group--Focus on Chronic Lymphatic Leukemia
J Natl Cancer Inst, August 6, 2008; 100(15): E1 - E1.
[Full Text] [PDF]

Home page
 BloodHome page
M. Hallek, B. D. Cheson, D. Catovsky, F. Caligaris-Cappio, G. Dighiero, H. Dohner, P. Hillmen, M. J. Keating, E. Montserrat, K. R. Rai, et al.
Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute-Working Group 1996 guidelines
Blood, June 15, 2008; 111(12): 5446 - 5456.
[Abstract] [Full Text] [PDF]

Home page
 haematolHome page
A. W. Hauswirth and U. Jager
Impact of cytogenetic and molecular prognostic markers on the clinical management of chronic lymphocytic leukemia
Haematologica, January 1, 2008; 93(1): 14 - 19.
[Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
F. Bosch, A. Ferrer, N. Villamor, M. Gonzalez, J. Briones, E. Gonzalez-Barca, E. Abella, S. Gardella, L. Escoda, E. Perez-Ceballos, et al.
Fludarabine, Cyclophosphamide, and Mitoxantrone as Initial Therapy of Chronic Lymphocytic Leukemia: High Response Rate and Disease Eradication
Clin. Cancer Res., January 1, 2008; 14(1): 155 - 161.
[Abstract] [Full Text] [PDF]

Home page
 ASH Education BookHome page
J. G. Gribben
Molecular Profiling in CLL
Hematology, January 1, 2008; 2008(1): 444 - 449.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
J. M. Flynn and J. C. Byrd
Have We Forgotten the Purpose of Phase III Studies?
J. Clin. Oncol., December 10, 2007; 25(35): 5553 - 5555.
[Full Text] [PDF]

Home page
 JCOHome page
B. Austen, A. Skowronska, C. Baker, J. E. Powell, A. Gardiner, D. Oscier, A. Majid, M. Dyer, R. Siebert, A. M. Taylor, et al.
Mutation Status of the Residual ATM Allele Is an Important Determinant of the Cellular Response to Chemotherapy and Survival in Patients With Chronic Lymphocytic Leukemia Containing an 11q Deletion
J. Clin. Oncol., December 1, 2007; 25(34): 5448 - 5457.
[Abstract] [Full Text] [PDF]

Home page
 haematolHome page
S. Stilgenbauer, S. Sander, L. Bullinger, A. Benner, E. Leupolt, D. Winkler, A. Krober, D. Kienle, P. Lichter, and H. Dohner
Clonal evolution in chronic lymphocytic leukemia: acquisition of high-risk genomic aberrations associated with unmutated VH, resistance to therapy, and short survival
Haematologica, September 1, 2007; 92(9): 1242 - 1245.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
M. R. Grever, D. M. Lucas, G. W. Dewald, D. S. Neuberg, J. C. Reed, S. Kitada, I. W. Flinn, M. S. Tallman, F. R. Appelbaum, R. A. Larson, et al.
Comprehensive Assessment of Genetic and Molecular Features Predicting Outcome in Patients With Chronic Lymphocytic Leukemia: Results From the US Intergroup Phase III Trial E2997
J. Clin. Oncol., March 1, 2007; 25(7): 799 - 804.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
N. E. Kay, S. M. Geyer, T. G. Call, T. D. Shanafelt, C. S. Zent, D. F. Jelinek, R. Tschumper, N. D. Bone, G. W. Dewald, T. S. Lin, et al.
Combination chemoimmunotherapy with pentostatin, cyclophosphamide, and rituximab shows significant clinical activity with low accompanying toxicity in previously untreated B chronic lymphocytic leukemia
Blood, January 15, 2007; 109(2): 405 - 411.
[Abstract] [Full Text] [PDF]

Home page
 ASH Education BookHome page
T. D. Shanafelt and N. E. Kay
Comprehensive Management of the CLL Patient: A Holistic Approach
Hematology, January 1, 2007; 2007(1): 324 - 331.
[Abstract] [Full Text] [PDF]

Home page
 ASH-SAPHome page
P. Venugopal and S. A. Gregory
Lymphoproliferative disorders
ASH Self-Assessment Program, January 1, 2007; 2007(1): 265 - 297.
[Full Text] [PDF]

Home page
 JCOHome page
A. Chanan-Khan, K. C. Miller, L. Musial, D. Lawrence, S. Padmanabhan, K. Takeshita, C. W. Porter, D. W. Goodrich, Z. P. Bernstein, P. Wallace, et al.
Clinical Efficacy of Lenalidomide in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia: Results of a Phase II Study
J. Clin. Oncol., December 1, 2006; 24(34): 5343 - 5349.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
T. D. Shanafelt, T. E. Witzig, S. R. Fink, R. B. Jenkins, S. F. Paternoster, S. A. Smoley, K. J. Stockero, D. M. Nast, H. C. Flynn, R. C. Tschumper, et al.
Prospective Evaluation of Clonal Evolution During Long-Term Follow-Up of Patients With Untreated Early-Stage Chronic Lymphocytic Leukemia
J. Clin. Oncol., October 1, 2006; 24(28): 4634 - 4641.
[Abstract] [Full Text] [PDF]

Home page
 ANN INTERN MEDHome page
T. D. Shanafelt, J. C. Byrd, T. G. Call, C. S. Zent, and N. E. Kay
Narrative review: initial management of newly diagnosed, early-stage chronic lymphocytic leukemia.
Ann Intern Med, September 19, 2006; 145(6): 435 - 447.
[Abstract] [Full Text] [PDF]

Home page
 Mayo Clin Proc.Home page
K. W. L. Yee and S. M. O'Brien
Chronic Lymphocytic Leukemia: Diagnosis and Treatment
Mayo Clin. Proc., August 1, 2006; 81(8): 1105 - 1129.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
T. D. Shanafelt, D. Jelinek, R. Tschumper, S. Schwager, G. Nowakowski, G. W. DeWald, and N. E. Kay
Cytogenetic Abnormalities Can Change During the Course of the Disease Process in Chronic Lymphocytic Leukemia
J. Clin. Oncol., July 1, 2006; 24(19): 3218 - 3219.
[Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
C. D. Bloomfield, K. Mrozek, and M. A. Caligiuri
Cancer and Leukemia Group B Leukemia Correlative Science Committee: Major Accomplishments and Future Directions.
Clin. Cancer Res., June 1, 2006; 12(11): 3564s - 3571s.
[Abstract] [Full Text] [PDF]

Home page
 ASH Education BookHome page
E. Montserrat
New Prognostic Markers in CLL
Hematology, January 1, 2006; 2006(1): 279 - 284.
[Abstract] [Full Text] [PDF]


About
JCO		 Editorial
Roster		 Advertising
Information		 Librarians &
Institutions		 Rights &
Permissions		 PDA Services

Copyright © 2006 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
Terms and Conditions of Use
  HighWire Press HighWire Press™ assists in the publication of JCO Online