Figure 1. Outcome according to CD33 genotype for SNP rs12459419 in 536 patients randomized to receive or not receive GO.(A) RFS.(B) OS.

468 blood® 25 JANUARY 2018| VOLUME 131, NUMBER 4 LETTERS TO BLOOD benefit in patients with intermediate-risk cytogenetics but no benefit in those with adverse-risk cytogenetics. 1 Several studies have also demonstrated that the response positively correlates with higher levels of membrane CD33 expression on leukemic blasts. 2-5 Data recently published by Lamba and colleagues further suggests that genotype at a common single nucleotide polymorphism (SNP) in the CD33 gene (rs12459419 CT) determines response to GO in patients aged 0 to 29 years with de novo AML treated on the randomized phase 3 Children’s Oncology Group trial AAMLL0531. 6 The SNP influences alternative splicing at CD33 exon 2 such that the C allele leads to expression of the full-length protein but the T allele is associated with increased levels of a truncated isoform lacking the external GO-binding domain. The authors found that only those patients with a homozygous CC genotype (; 50% of patients) had a favorable response to GO, with no clinical benefit in those with either the heterozygous CT or homozygous TT genotype. The impact of GO was greatest in the CC patients with favorable risk defined as favorable cytogenetics or the presence of NPM1 or CEBPA mutations. These data have important implications for the use of GO in AML, and are particularly pertinent in view of the recent approval by the US Food and Drug Administration of Mylotarg for treatment of AML. We therefore investigated whether similar results pertained to younger adult patients treated on UK Medical Research Council (MRC) AML15 (ISRCTN17161961) and National Cancer Research Institute (NCRI) AML17 (ISRCTN55675535) trials. Treatment protocols and outcomes were as reported previously. 7, 8 Informed patient consent was obtained in accordance with the Declaration of Helsinki, and ethical approval for tissue use was obtained from the Wales Research Ethics Committee 3.

Genomic DNA was available from 536 of 2063 patients who were entered into different GO randomizations in these trials, and a flowchart of patients studied is shown in supplemental Figure 1 (available on the Blood Web site). Of these, 25 patients were randomized to receive GO in induction and consolidation