Blood online
Home About Blood Authors Subscriptions Permission Advertising Public Access contact us
 

 
Advanced
Current Issue
First Edition
Archives
Submit to Blood
Search
American Society of Hematology
Meeting Abstracts
Email Alerts
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
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 Download to citation manager
Right arrow reprints & permissions
Right arrow Rights and Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kantarjian, H. M.
Right arrow Articles by Talpaz, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kantarjian, H. M.
Right arrow Articles by Talpaz, M.
Related Collections
Right arrow Neoplasia
Right arrow Clinical Trials and Observations
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

arrow to previous article Previous Article  |  Table of Contents  |  Next Article next article arrow

Blood, 15 May 2002, Vol. 99, No. 10, pp. 3547-3553

CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS

Imatinib mesylate (STI571) therapy for Philadelphia chromosome-positive chronic myelogenous leukemia in blast phase

Hagop M. Kantarjian, Jorge Cortes, Susan O'Brien, Francis J. Giles, Maher Albitar, Mary Beth Rios, Jianqin Shan, Stefan Faderl, Guillermo Garcia-Manero, Deborah A. Thomas, Debra Resta, and Moshe Talpaz

From the Departments of Leukemia, Hematopathology, and Bioimmunotherapy, The University of Texas MD Anderson Cancer Center, Houston, TX, and Novartis Oncology, East Hanover, NJ.

Molecular abnormalities caused by the hybrid Bcr-Abl gene are causally associated with the development and progression of Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia (CML). Imatinib mesylate (STI571), a specific Bcr-Abl tyrosine-kinase signal-transduction inhibitor, has shown encouraging activity in phase I and II studies of CML. Here, we describe the use of imatinib mesylate to treat 75 patients in blast-phase CML (median age, 53 years; 65 with nonlymphoid and 10 with lymphoid blasts), and compare the results with those of a historical control group treated with standard cytarabine-based therapy. Imatinib mesylate was given as oral doses at 300 to 1000 mg per day and was the first salvage therapy for 47 patients. The objective response rate was 52% (39 of 75 patients: 16 had complete and 3 had partial hematologic response; 12 had hematologic improvement; 7 returned to second chronic phase; and 1 had a complete response in extramedullary blastic disease). Response rates were not different between nonlymphoid and lymphoid groups. The cytogenetic response rate was 16% (12 patients: 5 complete, 3 partial [Ph+ below 35%], and 4 minor [Ph+, 34% to 90%]). The estimated median overall survival was 6.5 months; the estimated 1-year survival was 22%. Response to therapy (landmark analysis at 8 weeks) was associated with survival prolongation. Compared with standard cytarabine combinations, imatinib mesylate therapy was less toxic and produced a higher response rate (55% versus 29%, P = .001), longer median survival (7 versus 4 months, P = .04), and lower 4-week induction mortality (4% versus 15%, P = .07). Imatinib mesylate is currently being tested in combination with other drugs to improve the prognosis for blast-phase CML.

© 2002 by The American Society of Hematology.
 

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


This article has been cited by other articles:


Home page
 JNCI J Natl Cancer InstHome page
J. Wu, F. Meng, L.-Y. Kong, Z. Peng, Y. Ying, W. G. Bornmann, B. G. Darnay, B. Lamothe, H. Sun, M. Talpaz, et al.
Association Between Imatinib-Resistant BCR-ABL Mutation-Negative Leukemia and Persistent Activation of LYN Kinase
J Natl Cancer Inst, July 2, 2008; 100(13): 926 - 939.
[Abstract] [Full Text] [PDF]

Home page
 haematolHome page
F. Palandri, I. Iacobucci, F. Castagnetti, N. Testoni, A. Poerio, M. Amabile, M. Breccia, T. Intermesoli, F. Iuliano, G. Rege-Cambrin, et al.
Front-line treatment of Philadelphia positive chronic myeloid leukemia with imatinib and interferon-{alpha}: 5-year outcome
Haematologica, May 1, 2008; 93(5): 770 - 774.
[Abstract] [Full Text] [PDF]

Home page
 Journal of Pharmacy PracticeHome page
L. K. Kenealy, C. B. Christenson, and C. B. Williams
Current Therapies for Chronic Myeloid Leukemia
Journal of Pharmacy Practice, April 1, 2008; 21(2): 116 - 125.
[Abstract] [PDF]

Home page
 BloodHome page
J. Wu, F. Meng, H. Lu, L. Kong, W. Bornmann, Z. Peng, M. Talpaz, and N. J. Donato
Lyn regulates BCR-ABL and Gab2 tyrosine phosphorylation and c-Cbl protein stability in imatinib-resistant chronic myelogenous leukemia cells
Blood, April 1, 2008; 111(7): 3821 - 3829.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
M. Brave, V. Goodman, E. Kaminskas, A. Farrell, W. Timmer, S. Pope, R. Harapanhalli, H. Saber, D. Morse, J. Bullock, et al.
Sprycel for Chronic Myeloid Leukemia and Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia Resistant to or Intolerant of Imatinib Mesylate
Clin. Cancer Res., January 15, 2008; 14(2): 352 - 359.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
F. Palandri, I. Iacobucci, G. Martinelli, M. Amabile, A. Poerio, N. Testoni, S. Soverini, F. Castagnetti, A. De Vivo, M. Breccia, et al.
Long-Term Outcome of Complete Cytogenetic Responders After Imatinib 400 mg in Late Chronic Phase, Philadelphia-Positive Chronic Myeloid Leukemia: The GIMEMA Working Party on CML
J. Clin. Oncol., January 1, 2008; 26(1): 106 - 111.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
J. M. Goldman
How I treat chronic myeloid leukemia in the imatinib era
Blood, October 15, 2007; 110(8): 2828 - 2837.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
V. G. Oehler, T. Gooley, D. S. Snyder, L. Johnston, A. Lin, C. C. Cummings, S. Chu, R. Bhatia, S. J. Forman, R. S. Negrin, et al.
The effects of imatinib mesylate treatment before allogeneic transplantation for chronic myeloid leukemia
Blood, February 15, 2007; 109(4): 1782 - 1789.
[Abstract] [Full Text] [PDF]

Home page
 haematolHome page
G. Rosti, I. Iacobucci, S. Bassi, F. Castagnetti, M. Amabile, D. Cilloni, A. Poerio, S. Soverini, F. Palandri, G. R. Cambrin, et al.
Impact of age on the outcome of patients with chronic myeloid leukemia in late chronic phase: results of a phase II study of the GIMEMA CML Working Party
Haematologica, January 1, 2007; 92(1): 101 - 105.
[Abstract] [Full Text] [PDF]

Home page
 ASH-SAPHome page
D. P. Steensma and R. E. Richard
Myeloproliferative disorders
ASH Self-Assessment Program, January 1, 2007; 2007(1): 172 - 227.
[Full Text] [PDF]

Home page
 BloodHome page
M. Baccarani, G. Saglio, J. Goldman, A. Hochhaus, B. Simonsson, F. Appelbaum, J. Apperley, F. Cervantes, J. Cortes, M. Deininger, et al.
Evolving concepts in the management of chronic myeloid leukemia: recommendations from an expert panel on behalf of the European LeukemiaNet
Blood, September 15, 2006; 108(6): 1809 - 1820.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
N. von Bubnoff, P. W. Manley, J. Mestan, J. Sanger, C. Peschel, and J. Duyster
Bcr-Abl resistance screening predicts a limited spectrum of point mutations to be associated with clinical resistance to the Abl kinase inhibitor nilotinib (AMN107)
Blood, August 15, 2006; 108(4): 1328 - 1333.
[Abstract] [Full Text] [PDF]

Home page
 NEJMHome page
H. Kantarjian, F. Giles, L. Wunderle, K. Bhalla, S. O'Brien, B. Wassmann, C. Tanaka, P. Manley, P. Rae, W. Mietlowski, et al.
Nilotinib in imatinib-resistant CML and Philadelphia chromosome-positive ALL.
N. Engl. J. Med., June 15, 2006; 354(24): 2542 - 2551.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
P. Ault, H. Kantarjian, S. O'Brien, S. Faderl, M. Beran, M. B. Rios, C. Koller, F. Giles, M. Keating, M. Talpaz, et al.
Pregnancy Among Patients With Chronic Myeloid Leukemia Treated With Imatinib
J. Clin. Oncol., March 1, 2006; 24(7): 1204 - 1208.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
I. Iacobucci, G. Rosti, M. Amabile, A. Poerio, S. Soverini, D. Cilloni, N. Testoni, E. Abruzzese, E. Montefusco, E. Ottaviani, et al.
Comparison Between Patients With Philadelphia-Positive Chronic Phase Chronic Myeloid Leukemia Who Obtained a Complete Cytogenetic Response Within 1 Year of Imatinib Therapy and Those Who Achieved Such a Response After 12 Months of Treatment
J. Clin. Oncol., January 20, 2006; 24(3): 454 - 459.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
D. J. Barnes, D. Palaiologou, E. Panousopoulou, B. Schultheis, A. S.M. Yong, A. Wong, L. Pattacini, J. M. Goldman, and J. V. Melo
Bcr-Abl Expression Levels Determine the Rate of Development of Resistance to Imatinib Mesylate in Chronic Myeloid Leukemia
Cancer Res., October 1, 2005; 65(19): 8912 - 8919.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
M. Golemovic, S. Verstovsek, F. Giles, J. Cortes, T. Manshouri, P. W. Manley, J. Mestan, M. Dugan, L. Alland, J. D. Griffin, et al.
AMN107, a Novel Aminopyrimidine Inhibitor of Bcr-Abl, Has In vitro Activity against Imatinib-Resistant Chronic Myeloid Leukemia
Clin. Cancer Res., July 1, 2005; 11(13): 4941 - 4947.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
J.-P. J. Issa, V. Gharibyan, J. Cortes, J. Jelinek, G. Morris, S. Verstovsek, M. Talpaz, G. Garcia-Manero, and H. M. Kantarjian
Phase II Study of Low-Dose Decitabine in Patients With Chronic Myelogenous Leukemia Resistant to Imatinib Mesylate
J. Clin. Oncol., June 10, 2005; 23(17): 3948 - 3956.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
N. C. Wolff, D. R. Veach, W. P. Tong, W. G. Bornmann, B. Clarkson, and R. L. Ilaria Jr
PD166326, a novel tyrosine kinase inhibitor, has greater antileukemic activity than imatinib mesylate in a murine model of chronic myeloid leukemia
Blood, May 15, 2005; 105(10): 3995 - 4003.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
C. Cebo, I. A. Voutsadakis, S. Da Rocha, J.-H. Bourhis, A. Jalil, B. Azzarone, A. G. Turhan, M. Chelbi-Alix, S. Chouaib, and A. Caignard
Altered IFN{gamma} Signaling and Preserved Susceptibility to Activated Natural Killer Cell-Mediated Lysis of BCR/ABL Targets
Cancer Res., April 1, 2005; 65(7): 2914 - 2920.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
A. Quintas-Cardama, H. Kantarjian, M. Talpaz, S. O'Brien, G. Garcia-Manero, S. Verstovsek, M. B. Rios, K. Hayes, A. Glassman, B. N. Bekele, et al.
Imatinib mesylate therapy may overcome the poor prognostic significance of deletions of derivative chromosome 9 in patients with chronic myelogenous leukemia
Blood, March 15, 2005; 105(6): 2281 - 2286.
[Abstract] [Full Text] [PDF]

Home page
 ASH Education BookHome page
R. L. Ilaria Jr.
Pathobiology of Lymphoid and Myeloid Blast Crisis and Management Issues
Hematology, January 1, 2005; 2005(1): 188 - 194.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
H. Kantarjian, M. Talpaz, S. O'Brien, G. Garcia-Manero, S. Verstovsek, F. Giles, M. B. Rios, J. Shan, L. Letvak, D. Thomas, et al.
High-dose imatinib mesylate therapy in newly diagnosed Philadelphia chromosome-positive chronic phase chronic myeloid leukemia
Blood, April 15, 2004; 103(8): 2873 - 2878.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
G. Rosti, G. Martinelli, S. Bassi, M. Amabile, E. Trabacchi, B. Giannini, D. Cilloni, B. Izzo, A. De Vivo, N. Testoni, et al.
Molecular response to imatinib in late chronic-phase chronic myeloid leukemia
Blood, March 15, 2004; 103(6): 2284 - 2290.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
M. Okada, S. Adachi, T. Imai, K.-i. Watanabe, S.-y. Toyokuni, M. Ueno, A. S. Zervos, G. Kroemer, and T. Nakahata
A novel mechanism for imatinib mesylate-induced cell death of BCR-ABL-positive human leukemic cells: caspase-independent, necrosis-like programmed cell death mediated by serine protease activity
Blood, March 15, 2004; 103(6): 2299 - 2307.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
J.-P. J. Issa, G. Garcia-Manero, F. J. Giles, R. Mannari, D. Thomas, S. Faderl, E. Bayar, J. Lyons, C. S. Rosenfeld, J. Cortes, et al.
Phase 1 study of low-dose prolonged exposure schedules of the hypomethylating agent 5-aza-2'-deoxycytidine (decitabine) in hematopoietic malignancies
Blood, March 1, 2004; 103(5): 1635 - 1640.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
H. Kantarjian, S. O'Brien, J. Cortes, F. Giles, J. Shan, M. B. Rios, S. Faderl, S. Verstovsek, G. Garcia-Manero, W. Wierda, et al.
Survival Advantage with Imatinib Mesylate Therapy in Chronic-Phase Chronic Myelogenous Leukemia (CML-CP) after IFN-{alpha} Failure and in Late CML-CP, Comparison with Historical Controls
Clin. Cancer Res., January 1, 2004; 10(1): 68 - 75.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
A. Cashen, J. F. DiPersio, and H. Khoury
Does Early Imatinib-Induced Myelosuppression Predict Hematologic Responses in Patients With Advanced-Phase Chronic Myeloid Leukemia?
J. Clin. Oncol., November 15, 2003; 21(22): 4255 - 4256.
[Full Text] [PDF]

Home page
 BloodHome page
B. J. P. Huntly, F. Guilhot, A. G. Reid, G. Vassiliou, E. Hennig, C. Franke, J. Byrne, A. Brizard, D. Niederwieser, J. Freeman-Edward, et al.
Imatinib improves but may not fully reverse the poor prognosis of patients with CML with derivative chromosome 9 deletions
Blood, September 15, 2003; 102(6): 2205 - 2212.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
R. Nimmanapalli, L. Fuino, P. Bali, M. Gasparetto, M. Glozak, J. Tao, L. Moscinski, C. Smith, J. Wu, R. Jove, et al.
Histone Deacetylase Inhibitor LAQ824 Both Lowers Expression and Promotes Proteasomal Degradation of Bcr-Abl and Induces Apoptosis of Imatinib Mesylate-sensitive or -refractory Chronic Myelogenous Leukemia-Blast Crisis Cells
Cancer Res., August 15, 2003; 63(16): 5126 - 5135.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
B. J. P. Huntly, A. Bench, and A. R. Green
Double jeopardy from a single translocation: deletions of the derivative chromosome 9 in chronic myeloid leukemia
Blood, August 15, 2003; 102(4): 1160 - 1168.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
N. C. Wolff, J. A. Richardson, M. Egorin, and R. L. Ilaria Jr
The CNS is a sanctuary for leukemic cells in mice receiving imatinib mesylate for Bcr/Abl-induced leukemia
Blood, June 15, 2003; 101(12): 5010 - 5013.
[Abstract] [Full Text] [PDF]

Home page
 ANN INTERN MEDHome page
R. Kurzrock, H. M. Kantarjian, B. J. Druker, and M. Talpaz
Philadelphia Chromosome-Positive Leukemias: From Basic Mechanisms to Molecular Therapeutics
Ann Intern Med, May 20, 2003; 138(10): 819 - 830.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
K. Scotlandi, M. C. Manara, R. Strammiello, L. Landuzzi, S. Benini, S. Perdichizzi, M. Serra, A. Astolfi, G. Nicoletti, P.-L. Lollini, et al.
c-kit Receptor Expression in Ewing's Sarcoma: Lack of Prognostic Value but Therapeutic Targeting Opportunities in Appropriate Conditions
J. Clin. Oncol., May 15, 2003; 21(10): 1952 - 1960.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
J. E. Cortes, M. Talpaz, F. Giles, S. O'Brien, M. B. Rios, J. Shan, G. Garcia-Manero, S. Faderl, D. A. Thomas, W. Wierda, et al.
Prognostic significance of cytogenetic clonal evolution in patients with chronic myelogenous leukemia on imatinib mesylate therapy
Blood, May 15, 2003; 101(10): 3794 - 3800.
[Abstract] [Full Text] [PDF]

Home page
 J. Mol. Diagn.Home page
A. L. Nashed, K. W. Rao, and M. L. Gulley
Clinical Applications of BCR-ABL Molecular Testing in Acute Leukemia
J. Mol. Diagn., May 1, 2003; 5(2): 63 - 72.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
F. J. Giles, S. Faderl, D. A. Thomas, J. E. Cortes, G. Garcia-Manero, D. Douer, A. M. Levine, C. A. Koller, S. S. Jeha, S. M. O'Brien, et al.
Randomized Phase I/II Study of Troxacitabine Combined With Cytarabine, Idarubicin, or Topotecan in Patients With Refractory Myeloid Leukemias
J. Clin. Oncol., March 15, 2003; 21(6): 1050 - 1056.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
H. M. Kantarjian, M. Talpaz, S. O'Brien, F. Giles, G. Garcia-Manero, S. Faderl, D. Thomas, J. Shan, M. B. Rios, and J. Cortes
Dose escalation of imatinib mesylate can overcome resistance to standard-dose therapy in patients with chronic myelogenous leukemia
Blood, January 15, 2003; 101(2): 473 - 475.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
H. M. Kantarjian, J. E. Cortes, S. O'Brien, F. Giles, G. Garcia-Manero, S. Faderl, D. Thomas, S. Jeha, M. B. Rios, L. Letvak, et al.
Imatinib mesylate therapy in newly diagnosed patients with Philadelphia chromosome-positive chronic myelogenous leukemia: high incidence of early complete and major cytogenetic responses
Blood, January 1, 2003; 101(1): 97 - 100.
[Abstract] [Full Text] [PDF]