Intensified chemotherapy without SCT in infant ALL: results from COG P9407 (Cohort 3).
BACKGROUND
Infants with acute lymphoblastic leukemia (ALL) present with aggressive disease and a poor prognosis. Early relapse within 6-9 months of diagnosis is common. Approximately 75% of infants have MLL-rearranged (MLL-R) ALL with event free survival (EFS) ranging from 20% to 30%. Children's Oncology Group (COG) P9407 used shortened (46 weeks), intensified therapy to address early relapse and poor EFS.


METHODS
P9407 therapy was modified three times for induction toxicity resulting in three cohorts of therapy. One hundred forty-seven infants were enrolled in the third cohort.


RESULTS
We report an overall 5-year EFS and OS of 42.3 ± 6% and 52.9 ± 6.5% respectively. Poor prognostic factors included age ≤90 days at diagnosis, MLL-R ALL and white cell count ≥50,000/μl. For infants ≤90 days of age, the 5-year EFS was 15.5 ± 10.1% and 48.5 ± 6.7% for those >90 days (P < 0.0001). Among infants >90 days of age, 5-year EFS rates were 43.8 ± 8% for MLL-R versus 69.1 ± 13.6% for MLL-germline ALL (P < 0.0001).


CONCLUSIONS
Age ≤90 days at diagnosis was the most important prognostic factor. Despite shortened therapy with early intensification, EFS remained less than 50% overall in MLL-R ALL.
Texas Children's Cancer Center, Baylor College of Medicine, Houston, Texas.
ZoAnn E
ZE
Dreyer
Joanne M
JM
Hilden
Tamekia L
TL
Jones
Meenakshi
M
Devidas
Naomi J
NJ
Winick
Cheryl L
CL
Willman
Richard C
RC
Harvey
I-Ming
IM
Chen
Fred G
FG
Behm
Jeanette
J
Pullen
Brent L
BL
Wood
Andrew J
AJ
Carroll
Nyla A
NA
Heerema
Carolyn A
CA
Felix
Blaine
B
Robinson
Gregory H
GH
Reaman
Wanda L
WL
Salzer
Stephen P
SP
Hunger
William L
WL
Carroll
Bruce M
BM
Camitta
D000367:Age Factors; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D015321:Gene Rearrangement; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000401:mortality*; D012008:Recurrence; D012307:Risk Factors; D033581:Stem Cell Transplantation; D015996:Survival Rate
C497422:KMT2A protein, human; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase
COG P9407; Intensified therapy without SCT; infant ALL