title: Assessment of BCR-ABL1 transcript levels at 3 months is the only requirement for predicting outcome for patients with chronic myeloid leukemia treated with tyrosine kinase inhibitors.
abstract: OBJECTIVE
  We studied BCR-ABL1 transcript levels in patients with chronic myeloid leukemia in chronic phase (CML-CP) at 3, 6, and 12 months after starting imatinib to identify molecular milestones that would predict for overall survival (OS) and other outcomes more reliably than serial marrow cytogenetics.
  
  
  METHODS
  We analyzed 282 patients with CML-CP who received imatinib 400 mg/d as first-line therapy followed by dasatinib or nilotinib if treatment with imatinib failed. We used a receiver operating characteristic curve to identify the cutoffs in transcript levels at 3, 6, and 12 months that would best predict patient outcome. We validated our findings in an independent cohort of 95 patients treated elsewhere.
  
  
  RESULTS
  Patients with transcript levels of more than 9.84% (n = 68) at 3 months had significantly lower 8-year probabilities of OS (56.9% v 93.3%; P < .001), progression-free survival, cumulative incidence of complete cytogenetic response, and complete molecular response than those with higher transcript levels. Similarly, transcript levels of more than 1.67% (n = 87) at 6 months and more than 0.53% (n = 93) at 12 months identified high-risk patients. However, transcript levels at 3 months were the most strongly predictive for the various outcomes. When we compared OS for the groups defined molecularly at 6 and 12 months with the usual cytogenetic milestones, categorization by transcript numbers was the only independent predictor for OS (relative risk, 0.207; P < .001 and relative risk, 0.158; P < .001, respectively).
  
  
  CONCLUSIONS
  A single measurement of BCR-ABL1 transcripts performed at 3 months is the best way to identify patients destined to fare poorly, thereby allowing early clinical intervention.
authors: Department of Haematology, Imperial College London, Hammersmith Hospital, Du Cane Rd, London W12 0NN, United Kingdom. d.marin@imperial.ac.uk
authors: David
authors: D
authors: Marin
authors: Amr R
authors: AR
authors: Ibrahim
authors: Claire
authors: C
authors: Lucas
authors: Gareth
authors: G
authors: Gerrard
authors: Lihui
authors: L
authors: Wang
authors: Richard M
authors: RM
authors: Szydlo
authors: Richard E
authors: RE
authors: Clark
authors: Jane F
authors: JF
authors: Apperley
authors: Dragana
authors: D
authors: Milojkovic
authors: Marco
authors: M
authors: Bua
authors: Jiri
authors: J
authors: Pavlu
authors: Christos
authors: C
authors: Paliompeis
authors: Alistair
authors: A
authors: Reid
authors: Katayoun
authors: K
authors: Rezvani
authors: John M
authors: JM
authors: Goldman
authors: Letizia
authors: L
authors: Foroni
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001549:Benzamides; D018572:Disease-Free Survival; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D000068877:Imatinib Mesylate; D015466:Leukemia, Myeloid, Chronic-Phase / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011743:Pyrimidines / Q000627:therapeutic use*; D014158:Transcription, Genetic; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases; D016044:Fusion Proteins, bcr-abl