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Clinical heterogeneity in childhood acute lymphoblastic leukemia with 11q23 rearrangements
C-H Pui1, J M Chessells, B Camitta
1St. Jude Chidren's Research Hospital and University of Tennessee, Memphis, 38105, USA.
Insights
Acute lymphoblastic leukemia (ALL) with 11q23 abnormalities shows significant clinical differences. Certain genetic subtypes and early treatment responses strongly predict patient outcomes, highlighting the need for tailored therapies.
Area of Science:
- Pediatric Oncology
- Hematology
- Clinical Genetics
Background:
- Acute lymphoblastic leukemia (ALL) is a heterogeneous disease.
- 11q23 abnormalities are common in infant ALL and associated with poor prognosis.
- Understanding clinical heterogeneity is crucial for improving treatment strategies.
Purpose of the Study:
- To assess clinical heterogeneity in ALL patients with 11q23 abnormalities.
- To identify prognostic factors within specific cytogenetic subsets.
- To guide therapeutic strategies for high-risk patient groups.
Main Methods:
- Analysis of a large cohort (n=497) of infants, children, and young adults with ALL and 11q23 abnormalities.
- Data collected from 1983-1995 across multiple cooperative groups and institutions.
- Subgroup analyses based on age (infants vs. older children) and specific cytogenetic abnormalities (t(4;11), t(11;19), del(11)(q23)).
Main Results:
- Infants with t(4;11) ALL and poor prednisone response or age <3 months had dismal prognoses.
- Hematopoietic stem cell transplantation did not improve outcomes in t(4;11) ALL.
- Patients with t(11;19) ALL and T-lineage immunophenotype had better outcomes than B-lineage ALL.
- National Cancer Institute-Rome risk criteria were significant for del(11)(q23) ALL.
Conclusions:
- Significant clinical heterogeneity exists among and within ALL subgroups with 11q23 abnormalities.
- Prognostic factors vary by specific genetic abnormality and age.
- Identification of high-risk patients may facilitate the development of novel therapeutic approaches.
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.
