Imatinib mesylate therapy in chronic myeloid leukemia patients in stable complete cytogenic response after interferon-alpha results in a very high complete molecular response rate.
To determine the impact on minimal residual disease by switching to imatinib chronic phase chronic myeloid leukaemia (CP-CML) patients responsive to interferon-alpha (IFNalpha), in stable complete cytogenetic response (CCR) but with persistent PCR positivity. Twenty-six Philadelphia positive (Ph+) CML patients in stable CCR after IFNalpha but persistently positive at PCR analysis during this treatment, were given imatinib mesylate at standard dose. At enrolment into the study, median IFN treatment and CCR duration were 88 months (range 15-202) and 73 months (range 10-148), respectively. Imatinib treatment resulted in a progressive and consistent decline of the residual disease as measured by quantitative PCR (RQ-PCR) in all but one of the 26 patients; at the end of follow-up, after a median of 32 months (range 21-49) of treatment, a major molecular response (BCR/ABL levels <0.1) was reached in 20 patients (77%), and BCR/ABL transcripts were undetectable in 13 (50%). The achievement of molecular response was significantly correlated with post-IFN baseline transcript level (mean 1.194 for patients achieving complete molecular response versus 18.97 for those who did not; p<0.001), but not with other clinical/biological disease characteristics. These results indicate that patients induced into CCR by IFN treatment represent a subset with very favourable prognosis, which can significantly improve molecular response with imatinib and further support investigative treatment schedules combining these two drugs.
Alimena
Giuliana
G
Department of Cellular Biotechnologies and Hematology, University La Sapienza, Rome, Italy. alimena@bce.uniromal.it
Breccia
Massimo
M
Luciano
Luigia
L
Quarantelli
Fabrizio
F
Diverio
Daniela
D
Izzo
Barbara
B
De Angelis
Biagio
B
Mancini
Marco
M
Latagliata
Roberto
R
Carmosino
Ida
I
Nanni
Mauro
M
Picardi
Marco
M
Rotoli
Bruno
B
Mandelli
Franco
F
Pane
Fabrizio
F
D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001549:Benzamides; D016044:Fusion Proteins, bcr-abl / Q000187:drug effects*; D006801:Humans; D000068877:Imatinib Mesylate; D017404:In Situ Hybridization, Fluorescence; D016898:Interferon-alpha / Q000008:administration & dosage; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy*; D008875:Middle Aged; D018365:Neoplasm, Residual; D010879:Piperazines / Q000008:administration & dosage; D011743:Pyrimidines / Q000008:administration & dosage; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016896:Treatment Outcome
D001549:Benzamides; D016898:Interferon-alpha; D010879:Piperazines; D011743:Pyrimidines; D012333:RNA, Messenger; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl