Achieving a major molecular response at the time of a complete cytogenetic response (CCgR) predicts a better duration of CCgR in imatinib-treated chronic myeloid leukemia patients.
OBJECTIVE
Most patients with chronic-phase chronic myeloid leukemia (CML) who receive imatinib achieve a complete cytogenetic remission (CCgR) and low levels of BCR-ABL transcripts. CCgR is durable in the majority of patients but relapse occurs in a subset.


METHODS
To determine the potential of quantitative reverse transcription-PCR of BCR-ABL to predict cytogenetic relapse, we serially monitored residual disease in 97 CML patients with an imatinib-induced CCgR. Patients with late chronic phase CML after IFN-alpha failure were treated with imatinib (400 mg daily).


RESULTS
During the imatinib median follow-up time of 36 months (range, 12-54 months), disease monitoring occurred by cytogenetics and quantitative PCR. Twenty percent of patients experienced cytogenetic relapse at a median of 18 months after CCgR and a median of 24 months after starting imatinib. None of the possible prognostic factors studied in univariate and multivariate analyses seemed to predict for loss of cytogenetic response but the reduction of BCR-ABL transcript levels at the time of CCgR is an important prognostic factor.


CONCLUSIONS
In our study, we showed not only that achieving a major molecular remission at 12 months is predictive of a durable cytogenetic remission but also that patients who achieved a major molecular remission (expressed both as the BCR-ABL/beta2 microglobulin ratio % <0.0005 and as a 3-log reduction from median baseline value) already at the time of first achieving a CCgR have significantly longer cytogenetic remission durations than those without this magnitude of molecular response (P < 0.05).
Iacobucci
Ilaria
I
Institute of Hematology and Medical Oncology Seràgnoli, University of Bologna, Bologna, Italy.
Saglio
Giuseppe
G
Rosti
Gianantonio
G
Testoni
Nicoletta
N
Pane
Fabrizio
F
Amabile
Marilina
M
Poerio
Angela
A
Soverini
Simona
S
Bassi
Simona
S
Cilloni
Daniela
D
Bassan
Renato
R
Breccia
Massimo
M
Lauria
Francesco
F
Izzo
Barbara
B
Merante
Serena
S
Frassoni
Francesco
F
Paolini
Stefania
S
Montefusco
Enrico
E
Baccarani
Michele
M
Martinelli
Giovanni
G
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides; D023381:Endpoint Determination; D005260:Female; D016313:Genes, abl / Q000235:genetics*; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D018365:Neoplasm, Residual; D010879:Piperazines / Q000627:therapeutic use*; D011237:Predictive Value of Tests; D011379:Prognosis; D011743:Pyrimidines / Q000627:therapeutic use*; D012074:Remission Induction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D016896:Treatment Outcome; D001613:beta 2-Microglobulin
D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D001613:beta 2-Microglobulin; D000068877:Imatinib Mesylate