Quantification of free total plasma DNA and minimal residual disease detection in the plasma of children with acute lymphoblastic leukemia.
The analysis of total plasma DNA and the monitoring of leukemic clone-specific immunoglobulin and/or T-cell receptor gene rearrangements for the evaluation of minimal residual disease (MRD) in the plasma may be useful tools for prognostic purposes or for early detection of subclinical disease recurrence in children with acute lymphoblastic leukemia (ALL). The aim of this paper is to establish reference ranges for total plasma DNA concentrations and to test the feasibility of MRD measurements employing plasma DNA from children with ALL by using real-time quantitative (RQ)-PCR. Despite wide inter-individual variation, the median concentrations of total plasma DNA for 12 healthy donors (57 ng/ml), 21 children with ALL after day 4 of treatment initiation (62 ng/ml) and 13 children with other malignancies (76 ng/ml) were similar. However, ALL patients had significantly higher concentrations at diagnosis (277 ng/ml) and on treatment day 3 (248 ng/ml) before returning to normal afterwards. Early plasma DNA MRD kinetics could be established for 15 ALL patients and showed good concordance with bone marrow MRD. Plasma DNA was higher in children with ALL at diagnosis but returned to normal within the first four treatment days. Despite low concentrations of DNA, it is feasible to measure MRD kinetics in plasma DNA during ALL induction therapy by adapted real-time PCR methodologies.
Schwarz
Arne Kristian
AK
Department of Pediatric Hematology and Oncology, Hannover Medical School, Hanover, Germany.
Stanulla
Martin
M
Cario
Gunnar
G
Flohr
Thomas
T
Sutton
Rosemary
R
Möricke
Anja
A
Anker
Philippe
P
Stroun
Maurice
M
Welte
Karl
K
Bartram
Claus R
CR
Schrappe
Martin
M
Schrauder
André
A
D000293:Adolescent; D000483:Alleles; D002648:Child; D002675:Child, Preschool; D004247:DNA / Q000097:blood; D005260:Female; D015334:Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor; D006801:Humans; D007223:Infant; D008297:Male; D018365:Neoplasm, Residual / Q000097:blood / Q000175:diagnosis / Q000235:genetics; D016133:Polymerase Chain Reaction / Q000379:methods; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood / Q000175:diagnosis / Q000235:genetics; D011379:Prognosis
D004247:DNA