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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
Stephen P. Hunger,
Majilinde Z. Fall,
Bruce M. Camitta,
Andrew J. Carroll,
Michael P. Link,
Stephen J. Lauer,
Donald H. Mahoney,
D. Jeanette Pullen,
Jonathan J. Shuster,
C. Philip Steuber, and
Michael L. Cleary
From Section of Pediatric Hematology/Oncology, the Department of
Pediatrics; University of Colorado School of Medicine, Denver;
Section of Pediatric Hematology/Oncology, the Department
of Pediatrics and Laboratory of Experimental Oncology, the Department
of Pathology, Stanford University School of Medicine, CA; Midwest
Children's Cancer Center, Pediatric Hematology/Oncology, Milwaukee,
WI; University of Alabama, Laboratory of Medical Genetics, Birmingham;
Emory University, Pediatric Hematology/Oncology, Atlanta, GA; Baylor
University, the Department of Pediatric Oncology, Houston,
TX; University of Mississippi Medical Center, the Department of
Pediatric Hematology/Oncology, Jackson; and Pediatric Oncology Group
Statistical Office, University of Florida, Gainesville.
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 104- to 105-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.
Blood, Vol. 91 No. 3 (February 1), 1998:
pp. 1021-1028
© 1998 by The American Society of Hematology.

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