B-cell reconstitution after allogeneic SCT impairs minimal residual disease monitoring in children with ALL.
Minimal residual disease (MRD) detection using quantification of clone-specific Ig or TCR rearrangements before and after transplantation in children with high-risk ALL is an important predictor of outcome. The method and guidelines for its interpretation are very precise to avoid both false-negative and -positive results. In a group of 21 patients following transplantation, we observed detectable MRD positivities in Ig/TCR-based real-time quantitative PCR (RQ-PCR) leading to no further progression of the disease (11 of 100 (11%) total samples). We hypothesized that these positivities were mostly the result of nonspecific amplification despite the application of strict internationally agreed-upon measures. We applied two non-self-specific Ig heavy chain assays and received a similar number of positivities (20 and 15%). Nonspecific products amplified in these RQ-PCR systems differed from specific products in length and sequence. Statistical analysis proved that there was an excellent correlation of this phenomenon with B-cell regeneration in BM as measured by flow cytometry and Ig light chain-kappa excision circle quantification. We conclude that although Ig/TCR quantification is a reliable method for post transplant MRD detection, isolated positivities in Ig-based RQ-PCR systems at the time of intense B-cell regeneration must be viewed with caution to avoid the wrong indication of treatment.
Fronkova
E
E
Department of Paediatric Haematology/Oncology, 2nd Medical School, Charles University and University Hospital Motol, Prague, Czech Republic. eva.fronkova@lfmotol.cuni.cz
Muzikova
K
K
Mejstrikova
E
E
Kovac
M
M
Formankova
R
R
Sedlacek
P
P
Hrusak
O
O
Stary
J
J
Trka
J
J
D000293:Adolescent; D001402:B-Lymphocytes / Q000276:immunology*; D002051:Burkitt Lymphoma / Q000601:surgery*; D002675:Child, Preschool; D004273:DNA, Neoplasm / Q000235:genetics; D015321:Gene Rearrangement; D006801:Humans; D007223:Infant; D017710:Lymphocyte Transfusion; D008297:Male; D018365:Neoplasm, Residual / Q000175:diagnosis / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D033581:Stem Cell Transplantation; D014184:Transplantation, Homologous / Q000276:immunology*
D004273:DNA, Neoplasm