De-Escalating Therapy in Pediatric Acute Promyelocytic Leukemia

High cure rates are achieved in adults with acute promyelocytic leukemia (APML) using combined all-trans retinoic acid (ATRA) and arsenic trioxide, with or without anthracycline chemotherapy. Now, the Children's Oncology Group reports a multinational noninferiority trial of de-escalated induction therapy with ATRA plus arsenic trioxide in patients with APML aged 1 to 21. Standard-risk patients (white blood cell count <10,000/μL) received ATRA plus arsenic trioxide, and high-risk patients (WBC ≥10,000/μL) received the same treatment plus four doses of idarubicin. Following induction, all patients received four cycles of consolidation therapy with ATRA plus arsenic trioxide; no maintenance therapy was given.

During a median follow-up of 2 years, standard-risk patients (n=98) had an event-free survival (EFS) rate of 98% and overall survival (OS) rate of 99%; there was one death during induction therapy and one patient relapsed. Among high-risk patients (n=56), EFS was 96% and OS was 100%; there were no deaths and two relapses. These results were noninferior to those in a historical control group of pediatric patients in earlier chemotherapy-containing clinical trials (the primary endpoint). Toxicities included known side effects of ATRA/arsenic therapy, including leukocytosis, differentiation syndrome, and pseudotumor cerebri; 13% of patients had clinically significant bleeding or thrombosis during induction therapy, with no coagulopathy-related deaths.