1. ¹St Jude Children's Research Hospital, Memphis, TN, USA
2. ²University of Tennessee, Memphis TN, USA
3. ³UK Medical Research Council Childhood Leukaemia Working Party, UK
4. ⁴Children's Oncology Group, USA
5. ⁵French Acute Lymphoblastic Leukemia Cooperative Group, France
6. ⁶Associazione Italiana di Ematologia ed Oncologia Pediatrica, Italy
7. ⁷Berlin-Frankfurt Münster Study Group, Germany
8. ⁸Cooperative ALL Study Group, Germany
9. ⁹Dutch Childhood Leukemia Study Group, Netherlands
10. ¹⁰Dana Farber Cancer Institute, USA
11. ¹¹Harvard Medical School, USA
12. ¹²European Organization for Research and Treatment of Cancer, France and Belgium

Correspondence: Dr C-H Pui, St Jude Children's Research Hospital, 332 N. Lauderdale, Memphis, TN 38105, USA. Fax: +001 901 521 9005

Received 14 December 2002; Accepted 17 December 2002.

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 2312% s.e. for those with good response), or age less than 3 months (P=0.0003, 5-year EFS, 55% vs 23.44% 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, 8813 vs 4614%). 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, 648% (high risk) vs 836% (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.