Reply to I.H.I.M. Hollink et al
Authors: Frederik Damm, Michael Heuser, Arnold Ganser, Jürgen Krauter
Journal: Journal of Clinical Oncology (2010)

We thank Hollink et al 1 for their comments on our findings on WT1 single nucleotide polymorphism (SNP) rs16754 as an independent prognostic marker in acute myeloid leukemia (AML) with normal karyotype. 2In contrast to our study on 249 adult patients with cytogenetically normal (CN) AML, the authors found no prognostic impact for WT1 SNP rs16754 in 232 de novo pediatric patients with AML.This was also true when they only considered pediatric patients with CN-AML (n ϭ 85).Factors related to characteristics, treatment, and biology of patients may account for these different results.First, the two examined cohorts were different.Whereas we performed our analyses on a homogenous cohort of 249 patients with CN-AML, Hollink et al 1 studied the influence of WT1 SNP rs16754 in pediatric AML in general.However, if the survival analyses were restricted to patients with CN-AML (n ϭ 85 [37%] of 232 patients), the authors did not find a prognostic impact of WT1 SNP rs16754.It has to be taken into account, however, that the number of patients with CN-AML was small compared with the number in our cohort.Second, the prognostic effect of the WT1 SNP rs16754 might be dependent on the overall outcome for the patients in the analysis.Treatment response and overall survival in pediatric AML in general is clearly better than in adult patients with AML.Intensity of the treatment and cumulative dosages of anthracyclines and cytarabine are not significantly different between the pediatric Berlin-Frankfurt-Muenster-AML protocols and our adult trials.Our data suggested that WT1 SNP rs16754 might be associated with treatment sensitivity.The better overall chemotherapy sensitivity of pediatric patients might diminish the difference between treatment-sensitive and -insensitive patients, potentially explaining the discrepant results.The different prognostic impacts of other biomarkers in pediatric and adult AML underscore the differences in biology and treatment response between adult and pediatric AML: whereas, in adult AML, NPM1 exon 12 mutations only predicted for better response to induction therapy and a favorable overall survival in the absence of FLT3-internal tandem duplication, 3 the favorable prognostic impact of NPM1 mutations was not influenced by FLT3-internal tandem duplication in pediatric AML. 4 Another example is partial tandem duplications in the MLL gene.Although a rare event in pediatric AML with an incidence around 2% to 3%, 5 in adult AML, these aberrations occur in 7% to 10% and are associated with short remission duration. 6,7urthermore, one has to keep in mind that there have been several contradictory reports on the prognostic influence of WT1 mutations and the WT1 expression status.Acquired mutations of the WT1 gene have been reported in approximately 10% of patients with CN-AML and have been associated with poor prognosis in adult and pediatric patients with AML. 8-11However, the two largest studies 12,13 to date in pediatric and adult AML contradicted these results and found no independent prognostic impact of WT1 mutations in 842 and 617 patients with AML, respectively.Confirming results by Gaidzik et al 12 and our group, 2 Abbas et al 13 also found no prognostic