Relapsed childhood T-cell acute lymphoblastic leukemia and lymphoblastic lymphoma

Abstract

While outcomes for pediatric acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL) have improved dramatically in recent decades, relapsed and refractory disease remain a significant therapeutic challenge. This is particularly true for patients with T-cell ALL and LBL, where survival for patients with relapsed/refractory disease remains dismal. Recent efforts to comprehensively profile the genomics of T-ALL/LBL to improve understanding of disease biology have enhanced our ability to identify high-risk patients at diagnosis who are more likely to relapse and have also identified novel targets for precision medicines. Novel immunotherapies have transformed the treatment landscape for patients with B-cell ALL (B-ALL). Many immunotherapies are under investigation in clinical trials for patients with T-ALL/LBL and early results are very promising. Given these insights into disease biology and the development of targeted and immune-based treatments, it is reasonable to hope for improved patient outcomes, although challenges remain. In this review, we summarize the present state of understanding of the risk factors for relapse of T-ALL/LBL, established treatment regimens, and the promising small molecule inhibitors and immunotherapies with the potential to revolutionize the treatment of relapsed/refractory T-ALL/LBL.

Figure 1.

Whole genome, exome, and transcriptome sequencing of more than 1,300 cases of T-cell acute lymphoblastic leukemia has redefined the genetic landscape of T-cell acute lymphoblastic leukemia and created a new understanding of risk for relapse. (A) Cumulative incidence of relapse varies significantly depending on specific type of genomic alteration in the same gene (time in months). (B) Forest plot of T-cell acute lymphoblastic leukemia (T-ALL) comparing clinical outcome by event-free survival (EFS) for each of 15 subtypes compared to the whole, with significant associations (P<0.1) in red. (C) 15 T-ALL subtypes categorized into 4 risk groups, and subdivided by end of induction measurable residual disease (EOI MRD) (negative = MRD<0.1%) to stratify patients into outcome groups ranging from 5-year EFS 45-98%. adj.: adjusted; CI: Confidence Interval; HR: Hazard Ratio; OR: Odds Ratio; wt: wild-type. Adapted from Pölönen et al.