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.
Hilden
Joanne M
JM
The Children's Hospital at The Cleveland Clinic, OH 44195, USA. hildenj@ccf.org
Dinndorf
Patricia A
PA
Meerbaum
Sharon O
SO
Sather
Harland
H
Villaluna
Doojduen
D
Heerema
Nyla A
NA
McGlennen
Ron
R
Smith
Franklin O
FO
Woods
William G
WG
Salzer
Wanda L
WL
Johnstone
Helen S
HS
Dreyer
Zoann
Z
Reaman
Gregory H
GH
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