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.
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.
Fielding
Adele K
AK
University College London, London, United Kingdom. A.Fielding@medsch.ucl.ac.uk
Rowe
Jacob M
JM
Richards
Susan M
SM
Buck
Georgina
G
Moorman
Anthony V
AV
Durrant
I Jill
IJ
Marks
David I
DI
McMillan
Andrew K
AK
Litzow
Mark R
MR
Lazarus
Hillard M
HM
Foroni
Letizia
L
Dewald
Gordon
G
Franklin
Ian M
IM
Luger
Selina M
SM
Paietta
Elisabeth
E
Wiernik
Peter H
PH
Tallman
Martin S
MS
Goldstone
Anthony H
AH
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
D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D012333:RNA, Messenger; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases