title: Prospective outcome data on 267 unselected adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia confirms superiority of allogeneic transplantation over chemotherapy in the pre-imatinib era: results from the International ALL Trial MRC UKALLXII/ECOG2993.
abstract: Prospective data on the value of allogeneic hematopoietic stem cell transplantation (alloHSCT) in Philadelphia chromosome-positive (Ph(+)) acute lymphoblastic leukemia (ALL) are limited. The UKALLXII/ECOG 2993 study evaluated the outcome of assigning alloHSCT with a sibling (sib) or matched unrelated donor (MUD) to patients younger than 55 years of age achieving complete remission (CR). The CR rate of 267 patients, median age 40, was 82%. Twenty-eight percent of patients proceeded to alloHSCT in first CR. Age older than 55 years or a pre-HSCT event were the most common reasons for failure to progress to alloHSCT. At 5 years, overall survival (OS) was 44% after sib alloHSCT, 36% after MUD alloHSCT, and 19% after chemotherapy. After adjustment for sex, age, and white blood count and excluding chemotherapy-treated patients who relapsed or died before the median time to alloHSCT, only relapse-free survival remained significantly superior in the alloHSCT group (odds ratio 0.31, 95% confidence interval 0.16-0.61). An intention-to-treat analysis, using the availability or not of a matched sibling donor, showed 5-year OS to be nonsignificantly better at 34% with a donor versus 25% with no donor. This prospective trial in adult Ph(+) ALL indicates a modest but significant benefit to alloHSCT. This trial has been registered with clinicaltrials.gov under identifier NCT00002514 and as ISRCTN77346223.
authors.affiliation: University College London, London, United Kingdom. A.Fielding@medsch.ucl.ac.uk
authors.forename: Adele K
authors.initials: AK
authors.lastname: Fielding
authors.forename: Jacob M
authors.initials: JM
authors.lastname: Rowe
authors.forename: Susan M
authors.initials: SM
authors.lastname: Richards
authors.forename: Georgina
authors.initials: G
authors.lastname: Buck
authors.forename: Anthony V
authors.initials: AV
authors.lastname: Moorman
authors.forename: I Jill
authors.initials: IJ
authors.lastname: Durrant
authors.forename: David I
authors.initials: DI
authors.lastname: Marks
authors.forename: Andrew K
authors.initials: AK
authors.lastname: McMillan
authors.forename: Mark R
authors.initials: MR
authors.lastname: Litzow
authors.forename: Hillard M
authors.initials: HM
authors.lastname: Lazarus
authors.forename: Letizia
authors.initials: L
authors.lastname: Foroni
authors.forename: Gordon
authors.initials: G
authors.lastname: Dewald
authors.forename: Ian M
authors.initials: IM
authors.lastname: Franklin
authors.forename: Selina M
authors.initials: SM
authors.lastname: Luger
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Paietta
authors.forename: Peter H
authors.initials: PH
authors.lastname: Wiernik
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; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D000068877:Imatinib Mesylate; D016130:Immunophenotyping; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000473:pathology / Q000628:therapy; D010677:Philadelphia Chromosome; D010879:Piperazines / Q000627:therapeutic use*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D011379:Prognosis; D011446:Prospective Studies; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011743:Pyrimidines / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012074:Remission Induction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D012333:RNA, Messenger; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases