Best Practices in Adolescent and Young Adult Patients with Acute Lymphoblastic Leukemia: A Focus on Asparaginase

Abstract

The inclusion of asparaginase in chemotherapy regimens to treat acute lymphoblastic leukemia (ALL) has had a positive impact on survival in pediatric patients. Historically, asparaginase has been excluded from most treatment protocols for adolescent and young adult (AYA) patients because of perceived toxicity in this population, and this is believed to have contributed to poorer outcomes in these patients. However, retrospective analyses over the past 12 years have shown that 2-, 5-, and 7-year overall survival of AYA patients is significantly improved with pediatric versus adult protocols. The addition of asparaginase to adult protocols yielded high rates of first remission and improved survival. However, long-term survival remains lower compared with what has been seen in pediatrics. The notion that asparaginase is poorly tolerated by AYA patients has been challenged in multiple studies. In some, but not all, studies, the incidences of hepatic and pancreatic toxicities were higher in AYA patients, whereas the rates of hypersensitivity reactions did not appear to differ with age. There is an increased risk of venous thromboembolic events, and management with anti-coagulation therapy is recommended. Overall, the risk of therapy-related mortality is low. Together, this suggests that high-intensity pediatric protocols offer an effective and tolerable approach to treating ALL in the AYA population.

Keywords: acute lymphoblastic leukemia; adolescent; asparaginase; young adult.

FIG. 1.

Retrospective comparison of outcomes in adolescent and young adult (AYA) patients treated on pediatric and adult protocols. *2-year OS; **5-year OS; ***7-year OS. AIEOP, Italian Association of Pediatric Hematology and Oncology; CALGB, Cancer and Leukemia Group B; CCG, Children's Cancer Group; DCOG, Dutch Childhood Oncology Group; FRALLE-93, French ALL Cooperative Group; GIMEMA, Italian Group for Adult Hematologic Diseases; HOVON, Hemato-Oncology Cooperative Study Group; LALA-94, Leucemie Aiguë Lymphoblastique de l'Adulte; OS, overall survival.

FIG. 2.

Comparison of adverse events (AEs) in AYAs (n = 147) with the overall patient population (n = 940) in a compassionate-use trial of asparaginase Erwinia chrysanthemi.