Infant acute lymphoblastic leukemia with MLL gene rearrangements: outcome following intensive chemotherapy and hematopoietic stem cell transplantation.
Forty-four infants with acute lymphoblastic leukemia (ALL) characterized by MLL gene rearrangements were treated on a protocol of intensive chemotherapy followed by hematopoietic stem cell transplantation (HSCT) between November 1998 and June 2002. The remission induction rate was 91.0%, and the 3-year overall survival and event-free survival (EFS) rates, with 95% confidence intervals, were 58.2% (43.5%-72.9%) and 43.6% (28.5%-58.7%), respectively. Univariate analysis of EFS by presenting features indicated a poorer outcome in patients younger than 6 months of age with high white blood cell counts (>/= 100 x 10(9)/L; EFS rate, 9.4% versus 55.1% for all others, P = .0036) and in those with central nervous system invasion (EFS rate, 10.0% versus 56.9% for all others, P = .0073). The 3-year posttransplantation EFS rate for the 29 patients who underwent HSCT in first remission was 64.4% (46.4%-82.4%). In this subgroup, only the timing of HSCT (first remission versus others) was a significant risk factor by multivariate analysis (P < .0001). These results suggest that early introduction of HSCT, possibly with a less toxic conditioning regimen, may improve the prognosis for infants with MLL(+) ALL. Identification of subgroups or patients who respond well to intensified chemotherapy alone should have a high priority in future investigations.
Department of Hematology and Oncology, Hyogo Children's Hospital, Kobe, Japan.
Yoshiyuki
Y
Kosaka
Katsuyoshi
K
Koh
Naoko
N
Kinukawa
Yoshihiro
Y
Wakazono
Keiichi
K
Isoyama
Takanori
T
Oda
Yasuhide
Y
Hayashi
Shigeru
S
Ohta
Hiroshi
H
Moritake
Megumi
M
Oda
Yoshihisa
Y
Nagatoshi
Hisato
H
Kigasawa
Yasushi
Y
Ishida
Akira
A
Ohara
Ryouji
R
Hanada
Masahiro
M
Sako
Takeyuki
T
Sato
Shuki
S
Mizutani
Keizo
K
Horibe
Eiichi
E
Ishii
D000367:Age Factors; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000633:toxicity; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D015321:Gene Rearrangement; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D017254:Leukemic Infiltration; D007958:Leukocyte Count; D008297:Male; D051788:Myeloid-Lymphoid Leukemia Protein; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000401:mortality / Q000628:therapy*; D011379:Prognosis; D011519:Proto-Oncogenes / Q000235:genetics*; D012074:Remission Induction; D016019:Survival Analysis; D014157:Transcription Factors / Q000235:genetics*; D019172:Transplantation Conditioning / Q000009:adverse effects; D016896:Treatment Outcome
D004268:DNA-Binding Proteins; C497422:KMT2A protein, human; D014157:Transcription Factors; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase