The Clinicogenomic Landscape of Induction Failure in Childhood and Young Adult T-Cell Acute Lymphoblastic Leukemia

Authors

David O'Connor
Jonas Demeulemeester
Lucia Conde
Amy Kirkwood
Kent Fung
Foteini Papaleonidopoulou
Gianna Bloye
Nadine Farah
Sunniyat Rahman
Jeremy Hancock
Caroline Bateman
Sarah Inglott
Jon Mee
Javier Herrero
Peter Van Loo
Anthony V Moorman
Ajay Vora
Marc R Mansour

Publication Date

7-1-2023

Journal

Journal of Clinical Cancer

Abstract

PURPOSE: Failure to respond to induction chemotherapy portends a poor outcome in childhood acute lymphoblastic leukemia (ALL) and is more frequent in T-cell ALL (T-ALL) than B-cell ALL. We aimed to address the limited understanding of clinical and genetic factors that influence outcome in a cohort of patients with T-ALL induction failure (IF).

METHODS: We studied all cases of T-ALL IF on two consecutive multinational randomized trials, UKALL2003 and UKALL2011, to define risk factors, treatment, and outcomes. We performed multiomic profiling to characterize the genomic landscape.

RESULTS: IF occurred in 10.3% of cases and was significantly associated with increasing age, occurring in 20% of patients age 16 years and older. Five-year overall survival (OS) rates were 52.1% in IF and 90.2% in responsive patients (

CONCLUSION: The outcome of IF in T-ALL remains poor with current therapy. The lack of a unifying genetic driver suggests alternative approaches, particularly using immunotherapy, are urgently needed.

Keywords

Humans, Young Adult, Adolescent, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma, Treatment Outcome, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma, Hematopoietic Stem Cell Transplantation, T-Lymphocytes, Prognosis

Comments

Associated Data

PMID: 37098241