11q23/MLL rearrangement confers a poor prognosis in infants with acute lymphoblastic leukemia.
OBJECTIVE
Leukemic cell characteristics were analyzed in infants less than 1 year of age with acute lymphoblastic leukemia (ALL) to determine adverse prognostic factors that might explain the poor prognosis of this group.


METHODS
Treatment outcomes were analyzed according to the presenting clinical and laboratory features of 30 infants treated between May 1979 and April 1993. A stepwise multivariate regression model was used to identify the most important prognostic indicator with respect to event-free survival.


RESULTS
Infant ALL cases were characterized by high presenting leukocyte count (median, 87 x 10(9)/L), increased frequency of CNS leukemia (50%), and blast cells with a CD10- phenotype (67%), myeloid-associated antigen expression (48%), and 11q23/MLL rearrangement (68%). The 11q23/MLL involvement was correlated with age less than 6 months, CD10- phenotype, myeloid-associated antigen expression, and high leukocyte count. Although 11q23/MLL involvement, age less than 6 months, myeloid-associated antigen expression, and female sex were each significantly associated with an inferior treatment outcome, only rearranged 11q23/MLL emerged as an independent predictor of prognosis in multivariate analysis (P = .01). Infants with this genetic abnormality had a 4.7-fold (95% confidence interval, 1.3- to 17.0-fold) increased risk in adverse events compared to other infants.


CONCLUSIONS
The 11q23/MLL involvement of blast cells identifies a major subgroup of infant ALL cases that require an innovative treatment approach. Infants who lack this genetic abnormality have an intermediate prognosis and could be treated accordingly on risk-directed protocols.
Pui
C H
CH
Department of Hematology-Oncology, St Jude Children's Research Hospital, Memphis, TN 38101-0318.
Behm
F G
FG
Downing
J R
JR
Hancock
M L
ML
Shurtleff
S A
SA
Ribeiro
R C
RC
Head
D R
DR
Mahmoud
H H
HH
Sandlund
J T
JT
Furman
W L
WL
D002869:Chromosome Aberrations; D002880:Chromosomes, Human, Pair 11; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D015321:Gene Rearrangement; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D016130:Immunophenotyping; D007223:Infant; D008297:Male; D015999:Multivariate Analysis; D051788:Myeloid-Lymphoid Leukemia Protein; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000276:immunology / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D011379:Prognosis; D016016:Proportional Hazards Models; D011519:Proto-Oncogenes; D016019:Survival Analysis; D014157:Transcription Factors
D004268:DNA-Binding Proteins; C497422:KMT2A protein, human; D014157:Transcription Factors; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase