Adult patients with a type of acute lymphoblastic leukemia (ALL) may benefit from the use of response-based risk stratification and therapy intensification used in pediatric disease.
Early thymic precursor (ETP)-ALL is a subtype of T-cell ALL associated with high rates of intrinsic treatment resistance and a poor prognosis. Previous research in pediatric patients with ETP-ALL has shown that chemotherapy resistance associated with the disease is negated by the implementation of early response-based intensification strategies, thus improving prognosis. Similar studies involving adult patients with ETP-ALL are lacking.
Jonathan Bond, MD, PhD, Hôpital Necker-Enfants Malades (Paris, France), and colleagues performed comprehensive clinicobiologic, genetic, and survival analyses of adult patients with T-cell ALL from previous Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL) studies conducted in 2003 and 2005. Among the entire cohort of 213 adult patients, 47 (22.1%) exhibited ETP-ALL. Researchers evaluated the outcomes of adult ETP-ALL treated with pediatric-inspired GRAALL regimens that consisted of further therapy intensification with allogeneic stem-cell transplantation (allo-SCT) in the case of early treatment resistance.
Results of the study were published in the Journal of Clinical Oncology (published online June 12, 2017; doi:10.1200/JCO.2016.71.8585).
Similar to pediatric patients, adult patients exhibited high rates of mutations in factors involved in cytokine receptor and RAS signaling (62.2%), hematopoietic development (29.7%), and chemical modification of histones (48.6%). In contrast to pediatric patients, adult patients exhibited a modest rate of mutations in DNA methylation factor genes (32.4%).
“Taken together with the evident transcriptional heterogeneity between ETP and non-ETP groups found by RNA-sequencing profiling, this suggests that immunophenotypic definition of ETP-ALL identifies a biologic entity that is underpinned by similar genetic dysregulation in adults and children,” the researchers wrote.
Results of the analysis showed that despite expected high levels of early bone marrow chemotherapy resistance (87%), prognosis for adults with ETP-ALL treated with the GRAALL regimens was not inferior to the prognosis of the non-ETP-ALL group; the 5-year overall survival for patients with ETP-ALL was 59.6% (95% CI, 44.2%-72.0%) compared with 66.5% (95% CI, 58.7%-73.2%) for patients without ETP-ALL (P = .33).
Additionally, researchers found that allo-SCT benefited a large proportion of adult patients with ETP-ALL. Response-based risk stratification and therapy intensification succeeds in abrogating the poor prognosis of adult ETP-ALL, they concluded.—Zachary Bessette
