title: Clinical heterogeneity in childhood acute lymphoblastic leukemia with 11q23 rearrangements.
abstract: To assess the clinical heterogeneity among patients with acute lymphoblastic leukemia (ALL) and various 11q23 abnormalities, we analyzed data on 497 infants, children and young adults treated between 1983 and 1995 by 11 cooperative groups and single institutions. The substantial sample size allowed separate analyses according to age younger or older than 12 months for the various cytogenetic subsets. Infants with t(4;11) ALL had an especially dismal prognosis when their disease was characterized by a poor early response to prednisone (P=0.0005 for overall comparison; 5-year event-free survival (EFS), 0 vs 23+/-+/-12% s.e. for those with good response), or age less than 3 months (P=0.0003, 5-year EFS, 5+/-+/-5% vs 23.4+/-+/-4% for those over 3 months). A poor prednisone response also appeared to confer a worse outcome for older children with t(4;11) ALL. Hematopoietic stem cell transplantation failed to improve outcome in either age group. Among patients with t(11;19) ALL, those with a T-lineage immunophenotype, who were all over 1 year of age, had a better outcome than patients over 1 year of age with B-lineage ALL (overall comparison, P=0.065; 5-year EFS, 88+/-+/-13 vs 46+/-14%). In the heterogeneous subgroup with del(11)(q23), National Cancer Institute-Rome risk criteria based on age and leukocyte count had prognostic significance (P=0.04 for overall comparison; 5-year EFS, 64+/-+/-8% (high risk) vs 83+/-+/-6% (standard risk)). This study illustrates the marked clinical heterogeneity among and within subgroups of infants or older children with ALL and specific 11q23 abnormalities, and identifies patients at particularly high risk of failure who may benefit from innovative therapy.
authors.affiliation: St. Jude Chidren's Research Hospital and University of Tennessee, Memphis, 38105, USA.
authors.forename: C-H
authors.initials: CH
authors.lastname: Pui
authors.forename: J M
authors.initials: JM
authors.lastname: Chessells
authors.forename: B
authors.initials: B
authors.lastname: Camitta
authors.forename: A
authors.initials: A
authors.lastname: Baruchel
authors.forename: A
authors.initials: A
authors.lastname: Biondi
authors.forename: J M
authors.initials: JM
authors.lastname: Boyett
authors.forename: A
authors.initials: A
authors.lastname: Carroll
authors.forename: O B
authors.initials: OB
authors.lastname: Eden
authors.forename: W E
authors.initials: WE
authors.lastname: Evans
authors.forename: H
authors.initials: H
authors.lastname: Gadner
authors.forename: J
authors.initials: J
authors.lastname: Harbott
authors.forename: D O
authors.initials: DO
authors.lastname: Harms
authors.forename: C J
authors.initials: CJ
authors.lastname: Harrison
authors.forename: P L
authors.initials: PL
authors.lastname: Harrison
authors.forename: N
authors.initials: N
authors.lastname: Heerema
authors.forename: G
authors.initials: G
authors.lastname: Janka-Schaub
authors.forename: W
authors.initials: W
authors.lastname: Kamps
authors.forename: G
authors.initials: G
authors.lastname: Masera
authors.forename: J
authors.initials: J
authors.lastname: Pullen
authors.forename: S C
authors.initials: SC
authors.lastname: Raimondi
authors.forename: S
authors.initials: S
authors.lastname: Richards
authors.forename: H
authors.initials: H
authors.lastname: Riehm
authors.forename: S
authors.initials: S
authors.lastname: Sallan
authors.forename: H
authors.initials: H
authors.lastname: Sather
authors.forename: J
authors.initials: J
authors.lastname: Shuster
authors.forename: L B
authors.initials: LB
authors.lastname: Silverman
authors.forename: M G
authors.initials: MG
authors.lastname: Valsecchi
authors.forename: E
authors.initials: E
authors.lastname: Vilmer
authors.forename: Y
authors.initials: Y
authors.lastname: Zhou
authors.forename: P S
authors.initials: PS
authors.lastname: Gaynon
authors.forename: M
authors.initials: M
authors.lastname: Schrappe
mesh_terms: D000293:Adolescent; D000367:Age Factors; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001402:B-Lymphocytes / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D002880:Chromosomes, Human, Pair 11 / Q000648:ultrastructure*; D002888:Chromosomes, Human, Pair 19 / Q000648:ultrastructure; D002894:Chromosomes, Human, Pair 4 / Q000648:ultrastructure; D002899:Chromosomes, Human, Pair 9 / Q000648:ultrastructure; D015331:Cohort Studies; D003131:Combined Modality Therapy; D004268:DNA-Binding Proteins / Q000235:genetics; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D005060:Europe / Q000453:epidemiology; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D007223:Infant; D007958:Leukocyte Count; D008297:Male; D051788:Myeloid-Lymphoid Leukemia Protein; D014411:Neoplastic Stem Cells / Q000473:pathology; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D011241:Prednisone / Q000008:administration & dosage; D011379:Prognosis; D016016:Proportional Hazards Models; D011519:Proto-Oncogenes; D012189:Retrospective Studies; D012307:Risk Factors; D013601:T-Lymphocytes / Q000473:pathology; D014157:Transcription Factors; D014178:Translocation, Genetic; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology
chemical_list: D004268:DNA-Binding Proteins; C497422:KMT2A protein, human; D015514:Oncogene Proteins, Fusion; D014157:Transcription Factors; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase; D011241:Prednisone