Long-term follow-up of minimal residual disease in childhood acute lymphoblastic leukemia patients by polymerase chain reaction analysis of multiple clone-specific or malignancy-specific gene markers.
Two types of markers, namely the clone-specific markers including T-cell receptor (TCR) gamma, TCR delta, and Ig heavy-chain (IgH) gene rearrangements, and malignancy-specific fusion gene mRNA such as SIL-TAL-1, BCR-ABL, and HRX-partner genes, were investigated by molecular biology techniques in 65 Chinese patients with acute lymphoblastic leukemia (ALL). In combination, these markers were informative among 96% of patients. Minimal residual disease (MRD) was followed up in 23 of these patients with available materials over a period varying from 8 to 54 months with at least one leukemia-specific probe. In most children, MRD was decreased continuously to an ultimately undetectable level within 6 to 12 months after remission induction therapy. One patient exhibited low-level residual leukemic cells for 4 years before the MRD turned negative. Another patient remained in complete remission for 45 months, although a positive signal was detected at 34 months using TCR delta probe, but was negative with a TCR gamma marker which was positive at presentation. In three patients who relapsed, MRD either persisted through the clinical course or became positive and eventually increased 3-11 months before clinical relapse. These data suggested that the combined use of multiple gene markers is a valuable tool for the PCR-based MRD detection, since it can cover most ALL patients. Furthermore, long-term follow-up of MRD is helpful for determining the dosage as well as the period of maintenance chemotherapy and for predicting impending relapse.
Kuang
S
S
Shanghai Institute of Hematology, Rui-Jin Hospital, Shanghai Second Medical University (SSMU), China.
Gu
L
L
Dong
S
S
Cao
Q
Q
Xu
C
C
Huang
W
W
Su
X Y
XY
Huang
Q H
QH
Xie
J X
JX
Chen
S J
SJ
Chen
Z
Z
D001483:Base Sequence; D002051:Burkitt Lymphoma / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D016694:Gene Rearrangement, delta-Chain T-Cell Antigen Receptor / Q000235:genetics*; D015334:Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor / Q000235:genetics*; D005819:Genetic Markers; D006801:Humans; D007223:Infant; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D018365:Neoplasm, Residual; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*
D005819:Genetic Markers