Minimal residual disease assessment in childhood acute lymphoblastic leukaemia: a Swedish multi-centre study comparing real-time polymerase chain reaction and multicolour flow cytometry.
Minimal residual disease (MRD) assessment is a powerful prognostic factor for determining the risk of relapse in childhood acute lymphoblastic leukaemia (ALL). In this Swedish multi-centre study of childhood ALL diagnosed between 2002 and 2006, the MRD levels were analysed in 726 follow-up samples in 228 children using real-time quantitative polymerase chain reaction (RQ-PCR) of rearranged immunoglobulin/T-cell receptor genes and multicolour flow cytometry (FCM). Using an MRD threshold of 0·1%, which was the sensitivity level reached in all analyses, the concordance between RQ-PCR and FCM MRD values at day 29 was 84%. In B-cell precursor ALL, an MRD level of ≥0·1% at day 29 predicted a higher risk of bone marrow relapse (BMR) with both methods, although FCM was a better discriminator. However, considering the higher median MRD values achieved with RQ-PCR, a higher MRD cut-off (≥0·2%) improved the predictive capacity of RQ-PCR. In T-ALL, RQ-PCR was notably superior to FCM in predicting risk of BMR. That notwithstanding, MRD levels of ≥0·1%, detected by either method at day 29, could not predict isolated extramedullary relapse. In conclusion, the concordance between RQ-PCR and FCM was high and hence both methods are valuable clinical tools for identifying childhood ALL cases with increased risk of BMR.
Department of Genetics and Pathology, Uppsala University, Uppsala, Sweden. ingrid.thorn@akademiska.se
Ingrid
I
Thörn
Erik
E
Forestier
Johan
J
Botling
Britt
B
Thuresson
Carina
C
Wasslavik
Elisabet
E
Björklund
Aihong
A
Li
Eleonor
E
Lindström-Eriksson
Maria
M
Malec
Elisabeth
E
Grönlund
Kerstin
K
Torikka
Jesper
J
Heldrup
Jonas
J
Abrahamsson
Mikael
M
Behrendtz
Stefan
S
Söderhäll
Stefan
S
Jacobsson
Tor
T
Olofsson
Anna
A
Porwit
Gudmar
G
Lönnerholm
Richard
R
Rosenquist
Christer
C
Sundström
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D008297:Male; D018365:Neoplasm, Residual; D016133:Polymerase Chain Reaction / Q000379:methods; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis / Q000473:pathology; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis* / Q000473:pathology / Q000628:therapy; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis / Q000473:pathology; D011379:Prognosis; D016019:Survival Analysis