Survival benefit with imatinib mesylate therapy in patients with accelerated-phase chronic myelogenous leukemia--comparison with historic experience.
BACKGROUND
The effect of imatinib mesylate on survival in the accelerated phase of chronic myelogenous leukemia (CML) is unknown. The objectives of this study were to update the long-term experience with imatinib in patients who had accelerated-phase CML and to compare outcomes with historic experience.


METHODS
The outcomes of 176 patients who received treatment with imatinib were reviewed and compared with the outcomes of 213 historic control patients with accelerated-phase CML who received treatment with interferon-alpha or with other modalities.


RESULTS
With imatinib, the complete hematologic response rate was 82% versus a rate < or = 50% for others, and the complete cytogenetic response rate was 43% versus rates of 0-6% for others. The estimated 4-year survival rates were 53% with imatinib, 42% with interferon-alpha, and 0-21% for others. A multivariate analysis of the total population of 389 patients indicated that imatinib therapy (vs. other therapies) was an independent, favorable prognostic factor for survival (P < 0.0001; hazard rate, 0.62). A subset analysis that included only patients who were treated with imatinib and interferon-alpha (276 patients) also identified imatinib as an independent favorable prognostic factor (P < 0.0001; hazard rate, 0.65). The 3-month cytogenetic response to imatinib was associated with significantly different survival outcomes (P < 0.0001). A multivariate analysis that included pretreatment characteristics and 3-month cytogenetic response among 150 patients who received imatinib and were alive at 3 months identified only 2 adverse independent prognostic factors: lack of a cytogenetic response at 3 months (P < 0.001) and anemia (hemoglobin < 10 g/dL; P = 0.003). Patients who had neither factor (41%) had an estimated 4-year survival rate of 88%; in the other patients, the 4-year survival rate was < or = 60%. This may have implications in relation to subsequent therapy, because, according to the outcomes of patients who underwent allogeneic transplantation in accelerated phase at the authors' institution and from literature reports, the estimates of 5-year survival were 25-30%.


CONCLUSIONS
The current results suggest that imatinib improved survival compared with other therapies in patients with accelerated-phase CML.
Kantarjian
Hagop
H
Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA. hkantarj@mdanderson.org
Talpaz
Moshe
M
O'Brien
Susan
S
Giles
Francis
F
Faderl
Stefan
S
Verstovsek
Srdan
S
Garcia-Manero
Guillermo
G
Shan
Jianqin
J
Rios
Mary Beth
MB
Champlin
Richard
R
de Lima
Marcos
M
Cortes
Jorge
J
D000328:Adult; D000740:Anemia / Q000139:chemically induced; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides; D016026:Bone Marrow Transplantation; D015331:Cohort Studies; D020732:Cytogenetic Analysis; D005260:Female; D005500:Follow-Up Studies; D016044:Fusion Proteins, bcr-abl / Q000032:analysis; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D000068877:Imatinib Mesylate; D016898:Interferon-alpha / Q000627:therapeutic use; D015465:Leukemia, Myeloid, Accelerated Phase / Q000188:drug therapy*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011743:Pyrimidines / Q000627:therapeutic use*; D012074:Remission Induction; D015996:Survival Rate; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D001549:Benzamides; D006454:Hemoglobins; D016898:Interferon-alpha; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases; D016044:Fusion Proteins, bcr-abl