Medical College of Wisconsin
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E2A-PBX1 chimeric transcript status at end of consolidation is not predictive of treatment outcome in childhood acute lymphoblastic leukemias with a t(1;19)(q23;p13): a Pediatric Oncology Group study. Blood 1998 Feb 01;91(3):1021-8 PMID: 9446665

Pubmed ID

9446665

Abstract

A t(1;19)(q23;p13) is detected cytogenetically in approximately 5% of childhood acute lymphoblastic leukemias (ALLs) and its presence has been associated with an increased risk of relapse in several previously-completed Pediatric Oncology Group (POG) clinical trials. The t(1;19) fuses E2A to PBX1 in more than 95% of cases and this molecular abnormality can be reliably identified by polymerase chain reaction (PCR)-mediated amplification of E2A-PBX1 chimeric mRNAs. We used a nested PCR assay, which reproducibly detected a 10(4)- to 10(5)-fold dilution of t(1;19)+ into t(1;19)- cells, to evaluate minimal residual disease (MRD) in 48 children with t(1;19)+ ALL enrolled in POG clinical trials for lower (POG 9005) and higher (POG 9006) risk ALL. Peripheral blood (PB) and bone marrow (BM) samples were collected prospectively at the end of consolidation (weeks 25 and 31 after end of induction) and the presence or absence of PCR-detectable MRD was correlated with clinical outcome. Overall, 41 of 148 (28%) samples were PCR+. Of the 65 time points with informative results from both PB and BM, PCR results were concordant for 51 pairs (10 PB+/BM+, 41 PB-/ BM-) and discordant for 14 (5 PB+/BM-, 9 PB-/BM+), indicating that assessment of only PB or only BM can inaccurately classify some PCR+ cases as PCR-. There were no significant differences in event-free survival between PCR+ and PCR- patients. We conclude that qualitative detection of MRD by amplification of E2A-PBX1 chimeric mRNAs at the end of consolidation was not significantly predictive of outcome for children treated on POG 9005/9006 and that such results should not be used to alter therapy for patients with t(1;19)+ ALL.

Author List

Hunger SP, Fall MZ, Camitta BM, Carroll AJ, Link MP, Lauer SJ, Mahoney DH, Pullen DJ, Shuster JJ, Steuber CP, Cleary ML

Author

Bruce M. Camitta MD Clinical Professor in the Medicine department at Medical College of Wisconsin




Scopus

2-s2.0-18544407424   38 Citations

MESH terms used to index this publication - Major topics in bold

Antineoplastic Combined Chemotherapy Protocols
Chromosomes, Human, Pair 1
Chromosomes, Human, Pair 19
Disease-Free Survival
Homeodomain Proteins
Humans
Neoplasm, Residual
Oncogene Proteins, Fusion
Polymerase Chain Reaction
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Prognosis
Recurrence
Translocation, Genetic
Treatment Outcome
jenkins-FCD Prod-353 9ccd8489072cb19f5b9f808bb23ed672c582f41e