Quantitative polymerase chain reaction monitoring of BCR-ABL during therapy with imatinib mesylate (STI571; gleevec) in chronic-phase chronic myelogenous leukemia.
OBJECTIVE
The purpose of our investigation was to evaluate the response and minimal residual disease by quantitative competitive PCR (QC-PCR) studies in patients with chronic myeloid leukemia (CML) treated with imatinib mesylate.


METHODS
One hundred eighty patients with Philadelphia chromosome (Ph)-positive chronic-phase CML after IFN-alpha failure, treated with imatinib mesylate, had 543 simultaneous cytogenetic and QC-PCR analyses at different times during their therapy.


RESULTS
The median QC-PCR values [ratio-percentage of (BCR-ABL/ABL transcripts) x 100] for cytogenetic response categories were: no response (Ph, >90%), 36%; minor response (Ph, 35-90%), 22%; partial response (Ph, 1-34%), 7.3%; complete response (Ph, 0%), 0.89%. There was good correlation between cytogenetic and QC-PCR studies (P < 0.001; r = 0.92) and good concordance between QC-PCR values (>10%, 2-10%, and <2%) and cytogenetic response categories (none, minor, partial, complete) with a concordance rate of 66%, and major discordance of only 10%. Of 170 samples in complete cytogenetic response, 21% still had QC-PCR values of >10%, and 53% had QC-PCR values of <1%. There was excellent concordance between blood and marrow QC-PCR values (r = 0.965; P < 0.01; concordance rate, 88%; major discordance, 0%). No patient in complete cytogenetic response regardless of QC-PCR value has yet relapsed. At a median follow-up time of 26 months, higher QC-PCR values within each cytogenetic category at 3, 6, and 9 months have not been associated with a higher occurrence cytogenetic relapse or disease progression. However, the significance of this may become different with longer follow-up.


CONCLUSIONS
QC-PCR studies provide a useful tool to monitor patients with CML on imatinib mesylate therapy.
Kantarjian
Hagop M
HM
Departments of Leukemia, M D Anderson Cancer Center, Houston, Texas 77030, USA. hkantarj@mdanderson.org
Talpaz
Moshe
M
Cortes
Jorge
J
O'Brien
Susan
S
Faderl
Stefan
S
Thomas
Deborah
D
Giles
Francis
F
Rios
Mary Beth
MB
Shan
Jianqin
J
Arlinghaus
Ralph
R
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides; D018076:DNA, Complementary / Q000378:metabolism; D018450:Disease Progression; D016044:Fusion Proteins, bcr-abl / Q000378:metabolism*; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy*; D010879:Piperazines / Q000627:therapeutic use*; D016133:Polymerase Chain Reaction / Q000379:methods*; D011743:Pyrimidines / Q000627:therapeutic use*; D012313:RNA / Q000378:metabolism; D012008:Recurrence; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D001549:Benzamides; D018076:DNA, Complementary; D010879:Piperazines; D011743:Pyrimidines; D012313:RNA; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl