Treatment of philadelphia chromosome-positive, accelerated-phase chronic myelogenous leukemia with imatinib mesylate.
OBJECTIVE
Imatinib mesylate, a specific Bcr-Abl tyrosine kinase inhibitor, has shown encouraging activity in chronic myelogenous leukemia (CML).


METHODS
We treated 237 patients (median age, 50 years; age range, 18-82 years) with Philadelphia chromosome (Ph)-positive accelerated-phase CML with oral imatinib mesylate at daily doses of 400 mg (26 patients) or 600 mg (211 patients) and evaluated response and survival characteristics in univariate and multivariate analyses.


RESULTS
Among the 200 patients with accelerated-phase CML for whom follow-up was 3 months or more, rates of complete and partial hematological response were 80% and 10%. Cytogenetic responses were evident in 90 patients [45%; complete response in 47 patients (24%) and partial response (Ph 1-34%) in 21 patients (11%)]. The estimated 18-month survival rate was 73%. The estimated complete hematological response rate at 18 months was 68%; that for cytogenetic response was 82%. In multivariate analyses, a diagnosis-to-treatment interval of 3 years or more, splenomegaly, and peripheral blasts predicted poor major cytogenetic response; age >60 years, marrow basophilia, and clonal evolution predicted poor survival. The 600-mg drug dose was associated with better cytogenetic response and survival in univariate analysis (P < 0.01) but not in multivariate analysis. Landmark analysis showed that achieving a cytogenetic response at 3 months or a major cytogenetic response (Ph < 35%) at 6 months was associated with better long-term survival. Seven of 15 patients who were in a second chronic phase achieved major cytogenetic response. The incidence of severe nonhematological toxic effects was 23%; drug discontinuation for severe toxicity was needed in 3% of patients.


CONCLUSIONS
Imatinib mesylate was active against Ph-positive, accelerated-phase CML, and the prognostic factors identified in this study could aid in tailoring treatment strategies to specific risk groups.
Departments of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA. hkantarj@mdanderson.org
Hagop M
HM
Kantarjian
Susan
S
O'Brien
Jorge E
JE
Cortes
Terry L
TL
Smith
Mary Beth
MB
Rios
Jianqin
J
Shan
Ying
Y
Yang
Francis J
FJ
Giles
Deborah A
DA
Thomas
Stefan
S
Faderl
Guillermo
G
Garcia-Manero
Sima
S
Jeha
William
W
Wierda
Jean-Pierre J
JP
Issa
Steven M
SM
Kornblau
Michael
M
Keating
Debra
D
Resta
Renaud
R
Capdeville
Moshe
M
Talpaz
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides; D001853:Bone Marrow / Q000473:pathology; D020732:Cytogenetic Analysis; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000068877:Imatinib Mesylate; D015465:Leukemia, Myeloid, Accelerated Phase / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000627:therapeutic use*; D011379:Prognosis; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011743:Pyrimidines / Q000627:therapeutic use*; D015996:Survival Rate; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D001549:Benzamides; D004791:Enzyme Inhibitors; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases