RAS and TP53 Can Predict Survival in Adults with T-cell Lymphoblastic Leukemia Treated with Hyper-CVAD

Adult T-cell acute lymphoblastic leukemia (T-ALL) is a heterogeneous group of acute leukemias that account for about one third of all cases of Philadelphia chromosome (Ph)-negative ALL. Recently, a molecular classifier using the mutational status of NOTCH1, FBXW7, RAS, and PTEN (NFRP) has been shown to distinguish low- vs high-risk groups in adult T-ALL patients treated using the Berlin-Frankfurt-Münster ALL protocol. However, it is unknown if this molecular classifier can stratify adult T-ALL patients treated with hyper-CVAD ± nelarabine. We identified a relatively small cohort of 27 adults with T-ALL who were uniformly treated with hyper-CVAD ± nelarabine with available mutational analysis at time of diagnosis. The most commonly mutated genes in this group were NOTCH1 (52%), NRAS (22%), DNMT3A (19%), KRAS (15%), and TP53 (7%). The NFRP molecular classifier failed to stratify overall survival (OS; P = .84) and relapse-free survival (RFS; P = .18) in this cohort. We developed a new stratification model combining K/NRAS and TP53 mutations as high-risk factors and showed that mutations in these genes predicted poorer OS (P = .03) and RFS (P = .04). While the current study is limited by cohort size, these data suggest that the NFRP molecular classifier might not be applicable to adult T-ALL patients treated with hyper-CVAD ± nelarabine. RAS/TP53 mutation status, however, was useful in risk stratification in adults with T-ALL.