title: Molecular monitoring of imatinib in chronic myeloid leukemia patients in complete cytogenetic remission: does achievement of a stable major molecular response at any time point identify a privileged group of patients? A multicenter experience in Argentina and Uruguay.
abstract: BACKGROUND
  Monitoring minimal residual disease (MRD) by real-time quantitative polymerase chain reaction (RT-PCR) in chronic myeloid leukemia (CML) patients is mandatory in the era of tyrosine kinase inhibitors. Achieving a major molecular response (MMR) at 12 and 18 months predicts a better progression and event-free survival.
  
  
  METHODS
  The objective of this prospective, multicentric study was to evaluate MRD by standardized RT-PCR in 178 patients with chronic-phase CML who were treated with imatinib at different institutions in Argentina and Uruguay and to determine if achievement of a stable MMR (BCR-ABL transcript levels < 0.1%) identifies a low-risk cytogenetic relapse group. The median age of the patients was 50 years, and 55% of them had received imatinib as first-line therapy. BCR-ABL transcript levels were measured after achievement of complete cytogenetic remission (CCyR) and at 6-month intervals.
  
  
  RESULTS
  MMR was detected in 44% patients at the start of the study. This value increased to 79% at month 36 of evaluation. Complete molecular response (CMR) also increased from 24% to 52% of patients. Not achieving a stable MMR determined a higher risk of cytogenetic relapse (9% of MMR patients not achieving an MMR vs. 1% of patients who achieved MMR). Patients with sustained MMR had a significantly better cytogenetic relapse-free survival at 48 months (97% vs. 87%; P = .008) but showed no differences in overall survival. Patients who did not remain in CCyR changed treatment.
  
  
  CONCLUSIONS
  A stable MMR is a strong predictor for a durable CCyR. Standardized molecular monitoring could replace cytogenetic analysis once CCyR is obtained. These results emphasize the validity and feasibility of molecular monitoring in all standardized medical centers of the world.
authors.affiliation: FUNDALEU, Centro de Internación e Investigación Clínica Angélica Ocampo, Buenos Aires, Argentina. cpavlovsky@fundaleu.org.ar
authors.forename: Carolina
authors.initials: C
authors.lastname: Pavlovsky
authors.forename: Isabel
authors.initials: I
authors.lastname: Giere
authors.forename: Beatriz
authors.initials: B
authors.lastname: Moiraghi
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Pavlovsky
authors.forename: Pedro Negri
authors.initials: PN
authors.lastname: Aranguren
authors.forename: Juan
authors.initials: J
authors.lastname: García
authors.forename: Isolda
authors.initials: I
authors.lastname: Fernandez
authors.forename: Raquel
authors.initials: R
authors.lastname: Bengió
authors.forename: Jorge
authors.initials: J
authors.lastname: Milone
authors.forename: Valentin
authors.initials: V
authors.lastname: Labanca
authors.forename: Rosario
authors.initials: R
authors.lastname: Uriarte
authors.forename: Virginia
authors.initials: V
authors.lastname: Lombardi
authors.forename: Fernanda García
authors.initials: FG
authors.lastname: Reinoso
authors.forename: Alicia E
authors.initials: AE
authors.lastname: Magariños
authors.forename: Lem
authors.initials: L
authors.lastname: Martinez
authors.forename: Héctor
authors.initials: H
authors.lastname: Murro
authors.forename: Francisco
authors.initials: F
authors.lastname: Lastiri
authors.forename: Santiago
authors.initials: S
authors.lastname: Pavlovsky
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001118:Argentina; D001549:Benzamides; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000235:genetics; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D018365:Neoplasm, Residual / Q000175:diagnosis / Q000235:genetics; D010879:Piperazines / Q000627:therapeutic use*; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D012074:Remission Induction; D016019:Survival Analysis; D016896:Treatment Outcome; D014583:Uruguay; D055815:Young Adult
chemical_list: D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl