Analysis of prognostic factors of acute lymphoblastic leukemia in infants: report on CCG 1953 from the Children's Oncology Group.
Infant acute lymphoblastic leukemia (ALL) has a poor therapeutic outcome despite attempts to treat it based on prognostic factor-guided therapy. This is the first cooperative group trial characterizing all infants at the molecular level for MLL/11q23 rearrangement. All infants enrolled on Children's Cancer Group (CCG) 1953 were tested for MLL rearrangement by Southern blot and the 11q23 translocation partner was identified (4;11, 9;11, 11;19, or "other") by reverse-transcriptase polymerase chain reaction (PCR). One hundred fifteen infants were enrolled; overall event-free survival (EFS) was 41.7% (SD = 9.2%) and overall survival (OS) was 44.8% at 5 years. Five-year EFS for MLL-rearranged cases was 33.6% and for MLL-nonrearranged cases was 60.3%. The difference in EFS between the 3 major MLL rearrangements did not reach statistical significance. Multivariate Cox regression analyses showed a rank order of significance for negative impact on prognosis of CD10 negativity, age younger than 6 months, and MLL rearrangement, in that order. Toxicity was the most frequent cause of death. Relapse as a first event in CCG 1953 was later (median, 295 days) compared with CCG 1883 historic control (median, 207 days). MLL/11q23 rearrangement, CD10 expression, and age are important prognostic factors in infant ALL, but molecular 11q23 translocation partners do not predict outcome.
The Children's Hospital at The Cleveland Clinic, OH 44195, USA. hildenj@ccf.org
Joanne M
JM
Hilden
Patricia A
PA
Dinndorf
Sharon O
SO
Meerbaum
Harland
H
Sather
Doojduen
D
Villaluna
Nyla A
NA
Heerema
Ron
R
McGlennen
Franklin O
FO
Smith
William G
WG
Woods
Wanda L
WL
Salzer
Helen S
HS
Johnstone
Zoann
Z
Dreyer
Gregory H
GH
Reaman
D000367:Age Factors; D002423:Cause of Death; D002880:Chromosomes, Human, Pair 11; D018572:Disease-Free Survival; D005260:Female; D015321:Gene Rearrangement; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics; D015260:Neprilysin / Q000032:analysis; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000150:complications / Q000175:diagnosis* / Q000401:mortality; D011379:Prognosis; D016016:Proportional Hazards Models; D014178:Translocation, Genetic
C497422:KMT2A protein, human; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase; D015260:Neprilysin