title: UKALLXII/ECOG2993: addition of imatinib to a standard treatment regimen enhances long-term outcomes in Philadelphia positive acute lymphoblastic leukemia.
abstract: The Philadelphia chromosome positive arm of the UKALLXII/ECOG2993 study for adult acute lymphoblastic leukemia (ALL) enrolled 266 patients between 1993 and 2003 (pre-imatinib cohort). In 2003 imatinib was introduced as a single-agent course following induction (N = 86, late imatinib). In 2005 imatinib was added to the second phase of induction (N = 89, early imatinib). The complete remission (CR) rate was 92% in the imatinib cohort vs 82% in the preimatinib cohort (P = .004). At 4 years, the overall survival (OS) of all patients in the imatinib cohort was 38% vs 22% in the preimatinib cohort (P = .003). The magnitude of the difference between the preimatinib and imatinib cohorts in event-free survival (EFS), OS, and relapse-free survival (RFS) seen in univariate analysis was even greater in the multivariate analysis. In the preimatinib cohort, 31% of those starting treatment achieved hematopoietic stem cell transplant (alloHSCT) compared with 46% in the imatinib cohort. A Cox multivariate analysis taking alloHSCT into account showed a modest additional benefit to imatinib (hazard ratio for EFS = 0.64, 95% confidence interval 0.44-0.93, P = .02), but no significant benefit for OS and RFS. Adding imatinib to standard therapy improves CR rate and long-term OS for adults with ALL. A proportion of the OS benefit derives from the fact that imatinib facilitates alloHSCT. This trial was registered at clinicaltrials.gov as NCT00002514.
authors.affiliation: University College London, London, United Kingdom;
authors.forename: Adele K
authors.initials: AK
authors.lastname: Fielding
authors.forename: Jacob M
authors.initials: JM
authors.lastname: Rowe
authors.forename: Georgina
authors.initials: G
authors.lastname: Buck
authors.forename: Letizia
authors.initials: L
authors.lastname: Foroni
authors.forename: Gareth
authors.initials: G
authors.lastname: Gerrard
authors.forename: Mark R
authors.initials: MR
authors.lastname: Litzow
authors.forename: Hillard
authors.initials: H
authors.lastname: Lazarus
authors.forename: Selina M
authors.initials: SM
authors.lastname: Luger
authors.forename: David I
authors.initials: DI
authors.lastname: Marks
authors.forename: Andrew K
authors.initials: AK
authors.lastname: McMillan
authors.forename: Anthony V
authors.initials: AV
authors.lastname: Moorman
authors.forename: Bella
authors.initials: B
authors.lastname: Patel
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Paietta
authors.forename: Martin S
authors.initials: MS
authors.lastname: Tallman
authors.forename: Anthony H
authors.initials: AH
authors.lastname: Goldstone
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001549:Benzamides / Q000627:therapeutic use*; D015331:Cohort Studies; D003131:Combined Modality Therapy; D005260:Female; D005500:Follow-Up Studies; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D000068877:Imatinib Mesylate; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000401:mortality* / Q000628:therapy; D010677:Philadelphia Chromosome; D010879:Piperazines / Q000627:therapeutic use*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000401:mortality* / Q000628:therapy; D011379:Prognosis; D011743:Pyrimidines / Q000627:therapeutic use*; D012074:Remission Induction; D015996:Survival Rate; D014184:Transplantation, Homologous; D055815:Young Adult
chemical_list: D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate