Detection of Minimal Residual Disease in Acute Leukemia For

From www.bloodjournal.org by guest on February 6, 2015. For personal use only.
CORRESPONDENCE
2452
Detection of Minimal Residual Disease in Acute Leukemia
To the Editor:
Compana and Pui' have failed to mention in their well-balanced
and lucid review article on minimal residual disease (MRD) in leukemia two important practical aspects of quantitating MRD by polymerase chain reaction (PCR). First, the quantitation of MRD by PCR
is not precise, and the method based on Poisson statistics used by
Brisco et aI2 is no exception. If MRD quantitation were to be performed on the same sample on different days, up to twofold difference in the amount of MRD may be observed. This poor reproducibility should be kept in mind before changing treatment based on
the detection of MRD. Second, themethod of preparation of the
remission bone marrow for DNA extraction may also influence the
amount of MRD detected. For example, the PCR method is likely
to amplify target genes from DNA released from dead cells (not
clonogenic). The time taken for the bone marrowto remove the
dead leukemic cells may be variable depending on the initial leukemic load and the ability of the reticuloendothelial system to remove
the debris. DNA prepared from a buffy coat preparation or a whole
bone marrow suspension is more likely to contain DNA from dead
cells as opposed to DNA prepared from, eg, Hypaque-Ficoll-separated bone marrow cells.
These two practical issues may explain the wide variations in the
reported percentage of patients with MRDatthe
time of initial
remission (around 6 weeks from diagnosis) and might partly explain
the observation that the percentage of patients with detectable MRD
is lower in studies reporting MRD after several months from diagnosis.' These practical issues must be addressed in prospective studies
designed to validate the prognostic importance ofMRDin
acute
leukemia. It is premature to intensify therapy in patients with a high
amount ofMRD at the time of initial remission andto decrease
therapy in patients with no detectable MRD. It must be kept in mind
that prognosis in leukemia is relative to the txeatment and that good
results obtained in patients with no MRD may be because ofthe
currently available therapy, which is better than the therapy used 2
decades ago. To change the current practice in good prognosis patients may be an invitation for disaster.
R. Seshadri
Department of Hematology
Flinders Medical Centre
South Australia
REFERENCES
1. Campana D, Pui CH: Detection of minimal residual disease in
acute leukemia: Methodological advances and clinical significance.
Blood 85:1416, 1995
2. Brisco JM, Condon J, Hughes E, Neoh S, Sykes PJ, Williams
RH, Seshadri R, Toogood I, Waters K, Tauro G, Ekert H, Morley
AA: Prediction of outcome in childhood acute lymphoblastic leukaemia by molecular quantification of residual disease at the end of
induction. Lancet 343:196, 1994
3. Potter MN, Cross NCP, van Dongan JIM, Saglio A, Oakhill
CR, Bartram CR. Goldman J: Molecular evidence of minimal residual disease after treatment for leukemia and lymphoma: An updated
meeting report and review. Leukemia 8:1302, 1993
From www.bloodjournal.org by guest on February 6, 2015. For personal use only.
1995 86: 2452-2453
Expression of HLA-DR (major histocompatibility complex class II) on
neutrophils from patients treated with granulocyte-macrophage
colony- stimulating factor for mobilization of stem cells [letter]
SP Mudzinski, TP Christian, TL Guo, E Cirenza, KR Hazlett and EJ Gosselin
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