The clinical characteristics, therapy and outcome of 85 adults with acute lymphoblastic leukemia and t(4;11)(q21;q23)/MLL-AFF1 prospectively treated in the UKALLXII/ECOG2993 trial.
The biology and outcome of adult t(4;11)(q21;q23)/MLL-AFF1 acute lymphoblastic leukemia are poorly understood. We describe the outcome and delineate prognostic factors and optimal post-remission therapy in 85 consecutive patients (median age 38 years) treated uniformly in the prospective trial UKALLXII/ECOG2993. The immunophenotype of this leukemia was pro-B (CD10(NEG)). Immaturity was further suggested by high expression of the stem-cell antigens, CD133 and CD135, although CD34 expression was significantly lower than in t(4;11)-negative patients. Complete remission was achieved in 77 (93%) patients but only 35% survived 5 years (95% CI: 25-45%); the relapse rate was 45% (95% CI: 33-58%). Thirty-one patients underwent allogeneic transplantation in first remission (15 sibling donors and 16 unrelated donors): with 5-year survival rates of 56% and 67% respectively, only 2/31 patients relapsed. This compares with a 24% survival rate and 59% relapse rate in 46 patients who received post-remission chemotherapy. A major determinant of outcome was age with 71% of patients aged <25 years surviving. Younger patients had lower relapse rates (19%) but most received allografts in first complete remission. In conclusion, multivariate analysis did not demonstrate an advantage of allografting over chemotherapy but only five younger patients received chemotherapy. Prospective trials are required to determine whether poor outcomes in older patients can be improved by reduced-intensity conditioning allografts. NCT00002514 www.clinicaltrials.gov.
Adult BMT Unit, University Hospitals Bristol NHS Foundation Trust, Bristol, UK. David.Marks@UHBristol.nhs.uk
David I
DI
Marks
Anthony V
AV
Moorman
Lucy
L
Chilton
Elisabeth
E
Paietta
Amir
A
Enshaie
Gordon
G
DeWald
Christine J
CJ
Harrison
Adele K
AK
Fielding
Letizia
L
Foroni
Anthony H
AH
Goldstone
Mark R
MR
Litzow
Selina M
SM
Luger
Andrew K
AK
McMillan
Janis
J
Racevskis
Jacob M
JM
Rowe
Martin S
MS
Tallman
Peter
P
Wiernik
Hillard M
HM
Lazarus
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D002423:Cause of Death; D002880:Chromosomes, Human, Pair 11; D002894:Chromosomes, Human, Pair 4; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D008297:Male; D008875:Middle Aged; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D010641:Phenotype; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality / Q000628:therapy*; D011379:Prognosis; D011446:Prospective Studies; D012008:Recurrence; D012074:Remission Induction; D014178:Translocation, Genetic; D016896:Treatment Outcome; D055815:Young Adult
C113855:MLL-AF4 fusion protein, human; D015514:Oncogene Proteins, Fusion; D051788:Myeloid-Lymphoid Leukemia Protein