New Approaches to Treating Challenging Subtypes of ALL in AYA Patients
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ACUTE LYMPHOCYTIC LEUKEMIAS (K BALLEN AND M KENG, SECTION EDITORS)
New Approaches to Treating Challenging Subtypes of ALL in AYA Patients Kevin Prescott 1 & Michael Jacobs 1 & Wendy Stock 1 & Joseph Wynne 1
# Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Purpose of Review The treatment of acute lymphoblastic leukemia (ALL) in adolescent and young adult (AYA) patients has markedly improved with the adoption of pediatric-inspired protocols. However, there remain several subtypes of ALL that represent significant therapeutic challenges. Here, we review the current evidence guiding treatment of Philadelphia chromosome-positive (Ph+), Philadelphia chromosome-like (Ph-L), and early T-precursor (ETP) ALL in the AYA population. Recent Findings Clinical trials in Ph + ALL have demonstrated the superior efficacy of second- and third-generation tyrosine kinase inhibitors (TKIs) to induce and maintain remission. Current efforts now focus on determining the durability of these remissions and which patients will benefit from transplant. For Ph-like and ETP ALL, recent studies are investigating the addition of novel agents to standard treatment. Summary The treatment of Ph + ALL has significantly improved with the addition of potent TKIs. However, the treatment of Phlike and ETP ALL remains a challenge. At this time, the judicious use of allogenic transplant is the only current approach to modify this increased risk. Keywords ALL . AYA . ETP . Ph-like . Ph + ALL
Introduction It is well known that outcomes for acute lymphoblastic leukemia (ALL) worsen with age. Moreover, this worrisome trend has a significant inflection point in adolescence, where risk of relapse significantly increases compared with younger peers [1•]. Survival rates in children with ALL are upward of 80%, while the historical survival rate in adults is almost half of this, at roughly 40%. Over the last decade, dramatic improvements in this survival rate have been made in large part because of a paradigm shift in the treatment of young adults and adolescents (AYA) with ALL, with a new focus on treatment using pediatric-inspired chemotherapy regimens that rely on higher overall doses of steroids, vinca alkaloids, asparaginase, and intensive central nervous system (CNS) prophylaxis. This article is part of the Topical Collection on Acute Lymphocytic Leukemias * Joseph Wynne [email protected] 1
Department of Medicine, University of Chicago Medicine, 900 E. 57th Street, 8th Floor, Chicago, IL 60637, USA
Numerous studies have shown that by administering these regimens to patients up to 40 years of age, survival rates in this population can approach those of the pediatric population. This shift in treatment strategy for the AYA population was highlighted in a 2018 review in JAMA Oncology by Siegel et al., which revealed that 23 of 25 comparison studies assessing outcomes between pediatric and adult regimens for AYAs with ALL, in addition to one meta-analysis, favor the pediatric regimen [1•]. While the majority of studies incl
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