Document Detail


Effects of age on prognosis with imatinib mesylate therapy for patients with Philadelphia chromosome-positive chronic myelogenous leukemia.
MedLine Citation:
PMID:  12973833     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Older age is a consistent poor prognostic factor in patients with Philadelphia chromosome (Ph)-positive chronic myelogenous leukemia (CML). Whether this is related to an intrinsic worse disease biology or to inadequate drug delivery or excessive treatment-associated toxicity is unknown. The availability of imatinib mesylate, a selective, Bcr-Abl-targeted therapy that is administered orally with minimal side effects, may clarify whether older age would remain an adverse factor (thus, implying a different age-related CML biology). METHODS: Seven hundred forty-seven patients in different phases of Ph-positive CML who were treated with imatinib from 1999 until the time of last follow-up were evaluated. Among them, 187 patients had newly diagnosed, early chronic phase CML; 351 patients had chronic phase CML after interferon alpha (IFN) failure; 133 patients had accelerated phase CML; and 76 patients had blastic phase CML. The imatinib daily dose varied from 400 mg to 800 mg orally, according to the protocol design. Patients were categorized into a group of older patients (age 60 years or older) or younger patients (age younger than 60 years). Their characteristics, responses to therapy, and survival were compared by univariate and multivariate analyses. RESULTS: One hundred eighty-seven patients had newly diagnosed CML, and 49 patients (26%) were in the older age group. Older patients had similar cytogenetic response rates and survival compared with younger patients. Among 351 patients with late chronic phase CML after IFN failure, 120 patients (34%) were in the older age group. Although the older patients had a lower incidence of achievement of complete cytogenetic response (Ph, 0%) by univariate analysis (56% vs. 44%; P = 0.05), age was not found to be an independent poor prognostic factor in the multivariate analysis. Similarly, older age was not an adverse poor prognostic factor for survival. Forty-two of 133 patients (32%) with accelerated phase CML were older. The incidence of any cytogenetic response was lower in older patients (53% vs. 33%; P = 0.04), but age was not significant in the multivariate analysis. Older patients also had a trend toward worse survival (P = 0.09) that was not significant in the multivariate analysis. Twenty-eight of 76 patients (37%) evaluated in blastic phase were older. Older age was not a significant prognostic factor either for achieving response or for survival. CONCLUSIONS: With imatinib therapy, older age appears to have lost much of its prognostic relevance. This suggests that the previous poor prognosis observed with older age was related to treatment-associated factors (e.g., toxicity with allogeneic transplantation or with IFN therapy) rather than to an intrinsic, different disease biology of CML in older patients.
Authors:
Jorge Cortes; Moshe Talpaz; Susan O'Brien; Francis Giles; Mary Beth Rios; Jianquin Shan; Stefan Faderl; Guillermo Garcia-Manero; Alessandra Ferrajoli; William Wierda; Hagop Kantarjian
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cancer     Volume:  98     ISSN:  0008-543X     ISO Abbreviation:  Cancer     Publication Date:  2003 Sep 
Date Detail:
Created Date:  2003-09-15     Completed Date:  2003-09-30     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0374236     Medline TA:  Cancer     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1105-13     Citation Subset:  AIM; IM    
Copyright Information:
Copyright 2003 American Cancer Society.DOI 10.1002/cncr.11629
Affiliation:
Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA. hkantarj@mdanderson.org
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MeSH Terms
Descriptor/Qualifier:
Administration, Oral
Age Factors
Antineoplastic Agents / administration & dosage,  therapeutic use*
Enzyme Inhibitors / administration & dosage,  therapeutic use*
Humans
Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy*,  mortality
Middle Aged
Piperazines / administration & dosage,  therapeutic use*
Prognosis
Protein-Tyrosine Kinases / antagonists & inhibitors
Pyrimidines / administration & dosage,  therapeutic use*
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Enzyme Inhibitors; 0/Piperazines; 0/Pyrimidines; 152459-95-5/imatinib; EC 2.7.10.1/Protein-Tyrosine Kinases

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