Molecular response to imatinib in late chronic-phase chronic myeloid leukemia.
Imatinib is a tyrosine-kinase inhibitor that binds to ABL proteins and induces cytogenetic remissions in patients with chronic myeloid leukemia (CML). In these patients measuring response by molecular techniques is clearly required. We determined the cytogenetic and molecular response (CgR, MR) to imatinib in 191 patients with late chronic-phase Philadelphia-positive (Ph+) CML, previously treated with interferon alpha. MR was assessed with real-time quantitative (TaqMan) reverse transcription-polymerase chain reaction and was expressed as the ratio between BCR/ABL and beta 2-microglobulin x 100, the lowest level of detectability of the method being 0.00001. A complete CgR (CCgR) was achieved in 85 (44%) of 191 patients and was maintained for 2 years in 67 (79%) of 85 patients. A reduction of the transcript level of more than 2 logs was achieved in all but 9 patients with CCgR versus none of 23 with partial CgR. In the CCgRs the median value of the MR was 0.0008 after 12 months and 0.0001 after 24 months, with the transcript level undetectable in 22 cases. We conclude that in CCgRs the degree of MR may vary from 2 to more than 4 logs, and that there is a progressive decrease of transcript level by time. Only 1 of 22 negative cases has had a relapse as yet.
Rosti
Gianantonio
G
Institute of Hematology and Medical Oncology L. and A. Serànoli, University of Bologna, Italy.
Martinelli
Giovanni
G
Bassi
Simona
S
Amabile
Marilina
M
Trabacchi
Elena
E
Giannini
Barbara
B
Cilloni
Daniela
D
Izzo
Barbara
B
De Vivo
Antonio
A
Testoni
Nicoletta
N
Cambrin
Giovanna Rege
GR
Bonifazi
Francesca
F
Soverini
Simona
S
Luatti
Simona
S
Gottardi
Enrico
E
Alberti
Daniele
D
Pane
Fabrizio
F
Salvatore
Francesco
F
Saglio
Giuseppe
G
Baccarani
Michele
M
D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001549:Benzamides; D001854:Bone Marrow Cells / Q000502:physiology; D005500:Follow-Up Studies; D016313:Genes, abl / Q000235:genetics; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000503:physiopathology; D010879:Piperazines / Q000008:administration & dosage* / Q000009:adverse effects; D011743:Pyrimidines / Q000008:administration & dosage* / Q000009:adverse effects; D012008:Recurrence; D016896:Treatment Outcome; D001613:beta 2-Microglobulin / Q000235:genetics
D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D001613:beta 2-Microglobulin; D000068877:Imatinib Mesylate