T-cell acute lymphoblastic leukemia

Abstract

T-cell acute lymphoblastic leukemia (T-ALL) is biologically distinct from its B lymphoblastic (B-ALL) counterpart and shows different kinetic patterns of disease response. Although very similar regimens are used to treat T-ALL and B-ALL, distinctions in response to different elements of therapy have been observed. Similar to B-ALL, the key prognostic determinant in T-ALL is minimal residual disease (MRD) response. Unlike B-ALL, other factors including age, white blood cell count at diagnosis, and genetics of the ALL blasts are not independently prognostic when MRD response is included. Recent insights into T-ALL biology, using modern genomic techniques, have identified a number of recurrent lesions that can be grouped into several targetable pathways, including Notch, Jak/Stat, PI3K/Akt/mTOR, and MAPK. With contemporary chemotherapy, outcomes for de novo T-ALL have steadily improved and now approach those observed in B-ALL, with approximately 85% 5-year event-free survival. Unfortunately, salvage has remained poor, with less than 25% event-free and overall survival rates for relapsed disease. Thus, current efforts are focused on preventing relapse by augmenting therapy for high-risk patients, sparing toxicity in favorable subsets and developing new approaches for the treatment of recurrent disease.

Figure 1.

Day 29 (end induction) flow cytometry–based MRD response in ETP vs non-ETP ALL. The distribution of central flow cytometry–based MRD response at the end of induction in children and adolescents treated on COG study AALL0434 without ETP ALL are compared with MRD responses in the ETP ALL subset.

Figure 2.

EFS in ETP vs non-ETP ALL. Five-year EFS probabilities for patients treated on COG trial AALL0434 are depicted for ETP, near ETP, and T-ALL without an ETP phenotype (data cutoff 19 November 2014).