TY - JOUR
T1 - Demographic, clinical, and outcome features of children with acute lymphoblastic leukemia and CRLF2 deregulation
T2 - Results from the MRCALL97 clinical trial
AU - Ensor, Hannah M.
AU - Schwab, Claire
AU - Russell, Lisa J.
AU - Richards, Sue M.
AU - Morrison, Heather
AU - Masic, Dino
AU - Jones, Lisa
AU - Kinsey, Sally E.
AU - Vora, Ajay J.
AU - Mitchell, Christopher D.
AU - Harrison, Christine J.
AU - Moorman, Anthony V.
N1 - Copyright:
Copyright 2011 Elsevier B.V., All rights reserved.
PY - 2011/2/17
Y1 - 2011/2/17
N2 - Deregulated expression of CRLF2(CRLF2-d) arises via its juxtaposition to the IGH@enhancer or P2RY8 promoter. Among 865 BCP-ALL children treated on MRC ALL97, 52 (6%) had CRLF2-d, but it was more prevalent among Down syndrome patients (54%). P2RY8-CRLF2 (n = 43) was more frequent than IGH@-CRLF2 (n = 9). CRLF2-d was not associated with age, sex, or white cell count, but IGH@-CRLF2 patients were older than P2RY8-CRLF2 patients (median 8 vs 4 years, P = .0017). Patients with CRLF2-d were more likely to present with enlarged livers and spleens (38% vs 18%, P < .001). CRLF2-d was not seen in conjunction with established chromosomal translocations but 6 (12%) cases had high hyperdiploidy, and 5 (10%) had iAMP21. Univariate analysis suggested that CRLF2-d was associated with an inferior outcome: (event-free survival [EFS] hazard ratio 2.27 [95% confidence interval 1.48-3.47],P < .001;OS3.69 [2.34-5.84],P < .001). However, multivariate analysis indicated that its effect was mediated by other risk factors such as cytogenetics and DS status (EFS 1.45 [0.88-2.39], P = .140; OS 1.90 [1.08-3.36], P = .027). Although the outcome of IGH@-CRLF2 patients appeared inferior compared with P2RY8-CRLF2 patients, the result was not significant (EFS 2.69 [1.15-6.31],P = .023;OS2.86 [1.15-6.79],P = .021). Therefore, we concluded that patients with CRLF2-d should be classified into the intermediate cytogenetic risk group.
AB - Deregulated expression of CRLF2(CRLF2-d) arises via its juxtaposition to the IGH@enhancer or P2RY8 promoter. Among 865 BCP-ALL children treated on MRC ALL97, 52 (6%) had CRLF2-d, but it was more prevalent among Down syndrome patients (54%). P2RY8-CRLF2 (n = 43) was more frequent than IGH@-CRLF2 (n = 9). CRLF2-d was not associated with age, sex, or white cell count, but IGH@-CRLF2 patients were older than P2RY8-CRLF2 patients (median 8 vs 4 years, P = .0017). Patients with CRLF2-d were more likely to present with enlarged livers and spleens (38% vs 18%, P < .001). CRLF2-d was not seen in conjunction with established chromosomal translocations but 6 (12%) cases had high hyperdiploidy, and 5 (10%) had iAMP21. Univariate analysis suggested that CRLF2-d was associated with an inferior outcome: (event-free survival [EFS] hazard ratio 2.27 [95% confidence interval 1.48-3.47],P < .001;OS3.69 [2.34-5.84],P < .001). However, multivariate analysis indicated that its effect was mediated by other risk factors such as cytogenetics and DS status (EFS 1.45 [0.88-2.39], P = .140; OS 1.90 [1.08-3.36], P = .027). Although the outcome of IGH@-CRLF2 patients appeared inferior compared with P2RY8-CRLF2 patients, the result was not significant (EFS 2.69 [1.15-6.31],P = .023;OS2.86 [1.15-6.79],P = .021). Therefore, we concluded that patients with CRLF2-d should be classified into the intermediate cytogenetic risk group.
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U2 - 10.1182/blood-2010-07-297135
DO - 10.1182/blood-2010-07-297135
M3 - Article
C2 - 21106984
AN - SCOPUS:79951845044
VL - 117
SP - 2129
EP - 2136
JO - Blood
JF - Blood
SN - 0006-4971
IS - 7
ER -