Cytogenetic-specific heterogeneity in the kinetics of minimal residual disease (MIRD) clearance in childhood lymphoblastic leukaemia (ALL)

Moorman, A.V., Richards, S.M., Hancock, J.P., Mitchell, C.D., Vora, A.J., Harrison, C.J. and Goulden, N.J. (2008) Cytogenetic-specific heterogeneity in the kinetics of minimal residual disease (MIRD) clearance in childhood lymphoblastic leukaemia (ALL). British Journal of Haematology, 141, (Supplement 1), pp. 2. (doi:10.1111/j.1365-2141.2008.07061.x).


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Although both MRD and karyotype are powerful determinants of
outcome in childhood ALL, few studies have examined the kinetics of
MRD clearance by cytogenetics. In ALL2003, patients are stratified
by NCI criteria to a three or four drug induction. MRD is assessed at
day 29 and week 11 using a standardised and quality controlled RQPCR
of 21patient specific immunoglobulin or T-cell receptor
rearrangements. MRD risk groups were defined as: (1) High risk
MRD410-4 at day 29 (HR); (2) Low risk MRD negative or o10-4 at
day 29 and negative at week 11 (LR); or (3) MRD indeterminate risk.
Among 1000 patients entered into the trial, 98% were eligible for
these analyses, 94% had a successful cytogenetics and 57% were
assigned to a clinically relevant MRD groups. Among these latter 555
patients, 54% were MRD-HR whereas 45% were MRD-LR. Collectively,
patients with high-risk cytogenetics ‘t(9;22), o40 chromosomes,
11q23/MLL, t(17;19) and iAMP21’ were more likely to be MRDHR
‘83% vs 52%, P50.003’. Patients with ETV6-RUNX1 fusion were
less likely to be MRD-HR ‘28% vs 63%, Po0.001’ whereas high
hyperdiploid patients were more likely ‘64% vs 49%, P50.002’.
However, excluding ETV6-RUNX1 patients from the latter analysis
revealed that high hyperdiploid patients were as likely to be MRDHR
as other ETV6-RUNX1 negative patients. T-ALL patients were
also more likely to be MRD-HR compared to BCP-ALL patients ‘70%
vs 52%, P50.022’. In particular, 9/10 patients with t(5;14)/TLX3-
BCL11B fusion and 6/6 patients with SIL-TAL1 fusion were MRD-HR.
In conclusion, we have clearly demonstrated that MRD status varies
by cytogenetic subgroup with ETV6-RUNX1 patients having the
fastest MRD clearance rate. Despite the good prognosis associated
with high hyperdiploidy, these patients were as likely to be MRD-HR
as other standard risk patients. Longer follow-up is required to
determine the clinical significance of this finding.

Item Type: Article
Digital Object Identifier (DOI): doi:10.1111/j.1365-2141.2008.07061.x
Additional Information: Free Communications: Paediatric Malignancy 1 (p 1-121)
ISSNs: 0007-1048 (print)
Related URLs:
Keywords: children, minimal residual disease, disease, time
Subjects: R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
R Medicine > RJ Pediatrics
Divisions : University Structure - Pre August 2011 > School of Medicine > Cancer Sciences
ePrint ID: 62862
Accepted Date and Publication Date:
31 March 2008Published
Date Deposited: 07 Oct 2008
Last Modified: 31 Mar 2016 12:46

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