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Childhood Acute Lymphoblastic Leukemia With the MLL-ENL Fusion and t(11;19)(q23;p13.3) Translocation

From the St. Jude Children's Research Hospital; the University of Tennessee College of Medicine, Memphis, TN; the Pediatric Oncology Group Statistical Office, University of Florida, Gainesville, FL; the Pediatric Oncology Group Operations Office, Northwestern University, Chicago, IL; Stanford University, Stanford, CA; the University of Mississippi Medical Center, Jackson, MS; and the Midwest Children's Cancer Center, Milwaukee, WI.

Address reprint requests to Jeffrey E. Rubnitz, MD, PhD, Department of Hematology/Oncology, St. Jude Children's Research Hospital, 332 N Lauderdale St, Memphis, TN 38105–2794; Email: jeffrey.rubnitz@ stjude.org

PURPOSE: To determine the molecular characteristics, clinical features, and treatment outcomes of children with acute lymphoblastic leukemia (ALL) and the t(11;19)(q23;p13.3) translocation.

PATIENTS AND METHODS: A retrospective analysis of leukemic cell karyotypes obtained from patients with new diagnoses of ALL who were treated at St. Jude Children's Research Hospital or by the Pediatric Oncology Group was performed to identify cases with the t(11;19)(q23;p13.3) translocation. Molecular analyses were performed on these cases to determine the status of the MLL gene and the presence of the MLL-ENL fusion transcript.

RESULTS: Among 3,578 patients with ALL and successful cytogenetic analysis, we identified 35 patients with the t(11;19)(q23;p13.3) translocation: 13 infants and 11 older children had B-precursor leukemia, whereas 11 patients had a T-cell phenotype. Although all of the cases examined had MLL rearrangements and MLL-ENL fusion transcripts, outcome varied according to age and immunophenotype. Among B-precursor cases, only two of the 13 infants remain in complete remission, compared with six of the 11 older children. Most strikingly, no relapses have occurred among B-precursor patients 1 to 9 years of age or among T-cell patients.

CONCLUSION: Although MLL gene rearrangements are generally associated with a dismal outcome in ALL, two distinct subsets with MLL-ENL fusions have an excellent prognosis. Our results suggest that patients with this genetic abnormality who have T-cell ALL or are 1 to 9 years of age should not be considered candidates for hematopoietic stem-cell transplantation during their first remission.

This work was supported in part by National Institutes of Health (NIH) Cancer Center Support (CORE) grant CA-21,765; Childhood Cancer Genes Project grant CA-71907; Leukemia Program Project grant CA-20,180; NIH grants CA-29,139, CA-31,566, CA-30,969, CA-33,603, CA-15,989, and CA-32,053; and by the American Lebanese Syrian Associated Charities (ALSAC). J.E.R. is supported, in part, by a Career Development Award from the American Society of Clinical Oncology.

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