This project focused on reduction of the burden of therapy in young adults with Philadelphia chromosome-negative acute lymphoblastic leukemia (ALL); a privilege gained from the markedly improved survival in these patients with contemporary pediatric-based regimens. The price that comes with the pediatric approach characterized by the intensive asparaginase use is the introduction of a new toxicity profile different from that in children—with thromboembolism (TE) and asparaginase-associated pancreatitis (AAP) being associated with the most serious morbidities complicating delivery of key anti-leukemic agents at optimal doses and schedules and making physicians reluctant to use pediatric protocols for young adults despite the superior cure rates. 

We found a similar risk of AAP/TE between young adults and children, which is reassuring regarding the tolerance of young adults to the pediatric approach. However, given the association between older age and more serious TE subtypes with long-term sequelae, the strikingly higher odds for persisting AAP-related morbidities, and the high frequency of recurrent pancreatitis in young adults after asparaginase re-exposure, the re-exposure-decision must be balanced against the anticipated relapse risk. Last, age ≥10years; presence of enlarged lymph nodes; and mediastinal mass at ALL diagnosis as TE risk factors may inform warranted future RCTs of thromboprophylaxis. 

Kjeld Schmiegelow; professor, DMSc, MD (primary supervisor)

Ove Juul Nielsen; DMSc, MD

Nina Toft; PhD, MD