Management of hyperleukocytosis in pediatric acute myeloid leukemia using immediate chemotherapy without leukapheresis: results from the NOPHO-DBH AML 2012 Protocol

Abstract

Hyperleukocytosis (HL) in pediatric acute myeloid leukemia (AML) is associated with severe complications and inferior outcome. We report results on HL patients included in the NOPHO-DBH AML 2012 study. We recommended immediate start of full dose chemotherapy (etoposide [ETO] monotherapy for 5 days as part of the first course), avoiding leukapheresis (LA) and prephase chemotherapy (PCT).

Of 714 included patients, 122 (17.1%) had HL, and 111 were treated according to the recommendations with ETO upfront without preceding LA or PCT. The first dose was applied the same day as the AML diagnosis or the day after in 94%. ETO was administered via peripheral veins in 37% of patients without major complications. After initiation of ETO the remaining WBC on days 2-5 was 69%, 36%, 17% and 8% of the pre-treatment level. On day 3, 81% had a WBC<100 x109/L. Five-year event-free/overall survival (EFS/OS) for all HL patients was 52.9% (CI 44.4-63.0)/74.1 (66.4-82.6), compared to 64.9% (60.9-69.1)/78.9 (75.4-82.4), for non-HL patients (EFS P<0.001, OS P=0.1). Six-week early mortality was 4.1% for all HL patients (2.7% for the 111 patients treated with ETO upfront).

We conclude that management of HL in pediatric AML with immediate ETO monotherapy without LA/PCT is feasible, safe and effective. WBC reduction during the first days is comparable to reported results of LA, and outcomes seem at least equivalent to therapies including LA. Based on our results, we advocate abandoning LA in HL in pediatric AML. Instead, starting induction chemotherapy as early as ever possible is crucial.