TY - JOUR
T1 - Integrated use of minimal residual disease classification and IKZF1 alteration status accurately predicts 79% of relapses in pediatric acute lymphoblastic leukemia
AU - Waanders, E.
AU - van der Velden, V. H. J.
AU - van der Schoot, C. E.
AU - van Leeuwen, F. N.
AU - van Reijmersdal, S. V.
AU - de Haas, V.
AU - Veerman, A. J.
AU - van Kessel, A. Geurts
AU - Hoogerbrugge, P. M.
AU - Kuiper, R. P.
AU - van Dongen, J. J. M.
PY - 2011
Y1 - 2011
N2 - Response to therapy as determined by minimal residual disease (MRD) is currently used for stratification in treatment protocols for pediatric acute lymphoblastic leukemia (ALL). However, the large MRD-based medium risk group (MRD-M; 50-60% of the patients) harbors many relapses. We analyzed MRD in 131 uniformly treated precursor-B-ALL patients and evaluated whether combined MRD and IKZF1 (Ikaros zinc finger-1) alteration status can improve risk stratification. We confirmed the strong prognostic significance of MRD classification, which was independent of IKZF1 alterations. Notably, 8 of the 11 relapsed cases in the large MRD-M group (n = 81; 62%) harbored an IKZF1 alteration. Integration of both MRD and IKZF1 status resulted in a favorable outcome group (n = 104; 5 relapses) and a poor outcome group (n = 27; 19 relapses), and showed a stronger prognostic value than each of the established risk factors alone (hazard ratio (95%CI): 24.98 (8.29-75.31)). Importantly, whereas MRD and IKZF1 status alone identified only 46 and 54% of the relapses, respectively, their integrated use allowed prediction of 79% of all the relapses with 93% specificity. Because of the unprecedented sensitivity in upfront relapse prediction, the combined parameters have high potential for future risk stratification, particularly for patients originally classified as non-high risk, such as the large group of MRD-M patients. Leukemia (2011) 25, 254-258; doi:10.1038/leu.2010.275; published online 19 November 2010
AB - Response to therapy as determined by minimal residual disease (MRD) is currently used for stratification in treatment protocols for pediatric acute lymphoblastic leukemia (ALL). However, the large MRD-based medium risk group (MRD-M; 50-60% of the patients) harbors many relapses. We analyzed MRD in 131 uniformly treated precursor-B-ALL patients and evaluated whether combined MRD and IKZF1 (Ikaros zinc finger-1) alteration status can improve risk stratification. We confirmed the strong prognostic significance of MRD classification, which was independent of IKZF1 alterations. Notably, 8 of the 11 relapsed cases in the large MRD-M group (n = 81; 62%) harbored an IKZF1 alteration. Integration of both MRD and IKZF1 status resulted in a favorable outcome group (n = 104; 5 relapses) and a poor outcome group (n = 27; 19 relapses), and showed a stronger prognostic value than each of the established risk factors alone (hazard ratio (95%CI): 24.98 (8.29-75.31)). Importantly, whereas MRD and IKZF1 status alone identified only 46 and 54% of the relapses, respectively, their integrated use allowed prediction of 79% of all the relapses with 93% specificity. Because of the unprecedented sensitivity in upfront relapse prediction, the combined parameters have high potential for future risk stratification, particularly for patients originally classified as non-high risk, such as the large group of MRD-M patients. Leukemia (2011) 25, 254-258; doi:10.1038/leu.2010.275; published online 19 November 2010
U2 - https://doi.org/10.1038/leu.2010.275
DO - https://doi.org/10.1038/leu.2010.275
M3 - Article
C2 - 21102428
SN - 0887-6924
VL - 25
SP - 254
EP - 258
JO - Leukemia
JF - Leukemia
IS - 2
ER -