TY - JOUR
T1 - Impact of two independent bone marrow samples on minimal residual disease monitoring in childhood acute lymphoblastic leukaemia
AU - Van Der Velden, Vincent H.J.
AU - Hoogeveen, Patricia G.
AU - Pieters, Rob
AU - Van Dongen, Jacques J.M.
PY - 2006/5
Y1 - 2006/5
N2 - Minimal residual disease (MRD) diagnostics are used for risk group stratification in several acute lymphoblastic leukaemia (ALL) treatment protocols. It is, however, unclear whether MRD is homogeneously distributed within the bone marrow (BM) and whether this affects MRD diagnostics. We, therefore, analysed MRD levels in 141 paired BM samples (two independent punctures at different locations) from 26 ALL patients by real-time quantitative polymerase chain reaction (PCR) analysis of immunoglobulin and T-cell receptor gene rearrangements. MRD levels were comparable in 112 paired samples (79%), whereas two samples (both taken at day 15) had MRD levels that differed more than threefold. In the remaining 27 paired samples, MRD could be quantified or detected in one sample only. In four patients, MRD-based risk group classification was dependent on the site of BM puncture. Repetition of MRD analyses using 10-fold replicates instead of triplicates resolved most differences. In conclusion, MRD levels in paired BM samples were highly comparable, indicating that it is sufficient to analyse MRD in a single sample only. Nevertheless, MRD-based risk group classification can differ between paired BM samples, mainly because of variation below the quantitative range of the PCR assay rather than to a different distribution of leukaemic cells within the BM.
AB - Minimal residual disease (MRD) diagnostics are used for risk group stratification in several acute lymphoblastic leukaemia (ALL) treatment protocols. It is, however, unclear whether MRD is homogeneously distributed within the bone marrow (BM) and whether this affects MRD diagnostics. We, therefore, analysed MRD levels in 141 paired BM samples (two independent punctures at different locations) from 26 ALL patients by real-time quantitative polymerase chain reaction (PCR) analysis of immunoglobulin and T-cell receptor gene rearrangements. MRD levels were comparable in 112 paired samples (79%), whereas two samples (both taken at day 15) had MRD levels that differed more than threefold. In the remaining 27 paired samples, MRD could be quantified or detected in one sample only. In four patients, MRD-based risk group classification was dependent on the site of BM puncture. Repetition of MRD analyses using 10-fold replicates instead of triplicates resolved most differences. In conclusion, MRD levels in paired BM samples were highly comparable, indicating that it is sufficient to analyse MRD in a single sample only. Nevertheless, MRD-based risk group classification can differ between paired BM samples, mainly because of variation below the quantitative range of the PCR assay rather than to a different distribution of leukaemic cells within the BM.
KW - Acute lymphoblastic leukaemia
KW - Bone marrow
KW - Minimal residual disease
KW - RQ-PCR
KW - Sampling
UR - http://www.scopus.com/inward/record.url?scp=33645834105&partnerID=8YFLogxK
U2 - 10.1111/j.1365-2141.2006.06056.x
DO - 10.1111/j.1365-2141.2006.06056.x
M3 - Article
C2 - 16643444
AN - SCOPUS:33645834105
SN - 0007-1048
VL - 133
SP - 382
EP - 388
JO - British Journal of Haematology
JF - British Journal of Haematology
IS - 4
ER -