Dynamics of BCR-ABL mRNA expression in first-line therapy of chronic myelogenous leukemia patients with imatinib or interferon alpha/ara-C.
We sought to determine dynamics of BCR-ABL mRNA expression levels in 139 patients with chronic myelogenous leukemia (CML) in early chronic phase, randomized to receive imatinib (n=69) or interferon (IFN)/Ara-C (n=70). The response was sequentially monitored by cytogenetics from bone marrow metaphases (n=803) and qualitative and quantitative RT-PCR from peripheral blood samples (n=1117). Complete cytogenetic response (CCR) was achieved in 60 (imatinib, 87%) vs 10 patients (IFN/Ara-C, 14%) after a median observation time of 24 months. Within the first year after CCR, best median ratio BCR-ABL/ABL was 0.087%, (imatinib, n=48) vs 0.27% (IFN/Ara-C, n=9, P=0.025). BCR-ABL was undetectable in 25 cases by real-time PCR, but in only four patients by nested PCR. Median best response in patients with relapse after CCR was 0.24% (n=3) as compared to 0.029% in patients with continuous remission (n=52, P=0.029). We conclude that (i) treatment with imatinib in newly diagnosed CML patients is associated with a rapid decrease of BCR-ABL transcript levels; (ii) nested PCR may reveal residual BCR-ABL transcripts in samples that are negative by real-time PCR; (iii) BCR-ABL transcript levels parallel cytogenetic response, and (iv) imatinib is superior to IFN/Ara-C in terms of the speed and degree of molecular responses, but residual disease is rarely eliminated.
Müller
M C
MC
III. Medizinische Universitätsklinik, Fakultät für Klinische Medizin Mannheim der Universität Heidelberg, Mannheim, Germany.
Gattermann
N
N
Lahaye
T
T
Deininger
M W N
MW
Berndt
A
A
Fruehauf
S
S
Neubauer
A
A
Fischer
T
T
Hossfeld
D K
DK
Schneller
F
F
Krause
S W
SW
Nerl
C
C
Sayer
H G
HG
Ottmann
O G
OG
Waller
C
C
Aulitzky
W
W
le Coutre
P
P
Freund
M
M
Merx
K
K
Paschka
P
P
König
H
H
Kreil
S
S
Berger
U
U
Gschaidmeier
H
H
Hehlmann
R
R
Hochhaus
A
A
D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001549:Benzamides; D018592:Cross-Over Studies; D003561:Cytarabine / Q000008:administration & dosage; D003582:Cytogenetics; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D006801:Humans; D000068877:Imatinib Mesylate; D016898:Interferon-alpha / Q000008:administration & dosage*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage*; D011379:Prognosis; D011446:Prospective Studies; D011743:Pyrimidines / Q000008:administration & dosage*; D012333:RNA, Messenger / Q000378:metabolism; D012008:Recurrence; D012307:Risk Factors; D016896:Treatment Outcome
D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D001549:Benzamides; D016898:Interferon-alpha; D010879:Piperazines; D011743:Pyrimidines; D012333:RNA, Messenger; D003561:Cytarabine; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl