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Prospective monitoring and quantitation of residual blasts in childhood
acute lymphoblastic leukemia by polymerase chain reaction study of delta
and gamma T-cell receptor genes
H Cave, C Guidal, P Rohrlich, MH Delfau, A Broyart, B Lescoeur, C Rahimy, O Fenneteau, N Monplaisir and L d'Auriol
Hopital Robert Debre; Faculte Bichat, Paris, France.
We have developed a strategy based on polymerase chain reaction (PCR) for
detecting all possible gamma T-cell receptor (gamma TCR) rearrangements and
the most common delta TCR rearrangements found in B- lineage and T-acute
lymphoblastic leukemia (T-ALL). The segments amplified from blasts are then
directly sequenced to derive clonospecific probes. From a series of 45
patients aged 1 to 15 years (42 B-lineage ALL, 3 T-ALL), 35 (83%) could be
followed for minimal residual disease with at least one clonospecific
probe. Detection of clonal markers using clonospecific probes routinely
allowed the detection of 1 to 10 blasts out of 10(5) cells as determined by
serial dilutions of the initial samples. Residual disease was quantitated
by a competitive PCR assay based on the coamplification of an internal
standard. Twenty children were prospectively followed for periods varying
from 7 to 30 months. In most children, a progressive decrease of the tumor
load was observed, and blasts became undetectable within 6 months after the
initiation of treatment. A slower kinetics of decrease in tumor cells was
found in three children. These three patients relapsed with blasts that
continued to display the initial clonospecific markers. Three other
children had a central nervous system relapse despite the absence of
detectable medullary residual disease. The use of both delta and gamma TCR
genes as clonal markers, as well as simplification in the methods to detect
and quantify residual blasts reported here, will allow the study of the
large number of patients required to determine the role of the detection of
minimal residual disease by PCR in the follow-up of childhood ALL.
Volume 83,
Issue 7,
pp. 1892-1902,
04/01/1994
Copyright © 1994 by The American Society of Hematology
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