Standardization of flow cytometric minimal residual disease evaluation in acute lymphoblastic leukemia: Multicentric assessment is feasible.
BACKGROUND
Single-laboratory experience showed that flow cytometric (FCM) assessment of minimal residual disease (MRD) in acute lymphoblastic leukemia (ALL) is feasible in most patients and gives independent prognostic information. It is, however, not known whether FCM analysis can reliably be standardized for multicentric application.


METHODS
An extensive standardization program was installed in four collaborating laboratories, which study FCM-MRD in children treated with the AIEOP-BFM-ALL 2000 protocol. This included methodological alignment, continuous quality monitoring, as well as personnel education by exchange and performance feed-back.


RESULTS
Blinded inter-laboratory tests of list-mode data interpretation concordance (n = 202 blood and bone marrow samples from follow-up during induction of 31 randomly selected patients of a total series of n = 395) showed a very high degree of inter-rater agreement among the four centers despite differences in cytometers and software usage (intraclass correlation coefficient [ICC] 0.979 based on n= 800 single values). Lower concordance was reached with amounts of MRD below 0.1%. Comparing data from sample exchange experiments (n = 42 samples; ICC 0.98) and from independent patient cohorts from the four centers (regarding positive samples per time-point of follow-up as well as risk estimates) concordance was also good.


CONCLUSIONS
MRD-evaluation by FCM in ALL can be standardized for reliable multicentric assessment in large trials.
Children's Cancer Research Institute and St. Anna Children's Hospital, Vienna, Austria. michael.dworzak@stanna.at
Michael Norbert
MN
Dworzak
Giuseppe
G
Gaipa
Richard
R
Ratei
Marinella
M
Veltroni
Angela
A
Schumich
Oscar
O
Maglia
Leonid
L
Karawajew
Allessandra
A
Benetello
Ulrike
U
Pötschger
Zvenyslava
Z
Husak
Helmut
H
Gadner
Andrea
A
Biondi
Wolf-Dieter
WD
Ludwig
Giuseppe
G
Basso
D000293:Adolescent; D015703:Antigens, CD / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D005434:Flow Cytometry; D006801:Humans; D007223:Infant; D015337:Multicenter Studies as Topic; D018365:Neoplasm, Residual; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000473:pathology*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
D015703:Antigens, CD