Data Challenge Current Criteria for Complete Remission in Pediatric AML

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Researchers from Germany suggest the utility of platelet and absolute neutrophil counts may be misplaced in current standards for pediatric remission.

The previous definition for complete remission among patients with acute myeloid leukemia (AML) requires revision based on newer data, according to a group of investigators.

In a new abstract presented at the American Society of Hematology (ASH) 2022 Annual Meeting in New Orleans this week, a team of Germany clinicians argued that current criteria defining pediatric AML complete remission should be omitted in place of a more simplified criteria.

Led by Evangelia Antoniou, MD, of the University Hospital of Essen and AML-BFM Study Group, investigators reviewed current standards for complete remission before providing evidence and argument against its utility. As they noted, the traditional definition of pediatric AML complete remission is <5% blasts, absolute neutrophil count (ANC) <1000/mcL and platelets >80,000/mcL—the latter marker being a deviation from the adult standard of >100,000/mcL.

“This largely morphologically based definition has remained unchanged for more than 2 decades,” Antoniou and colleagues wrote. “Though proven as a valuable predictor of outcome and survival in clinical practice and trials, awaiting complete hematopoietic recovery still displays a hurdle of unknown prognostic significance in clinical practice.”

What’s more, a significant variety of diverse criteria with consideration to hematopoietic recovery were established in clinical trials in order to overcome this hurdle. As such, investigators argued the relevance of including ANC and platelets in the current complete remission definition should be reconsidered.

They cited data including 1051 pediatric patients with AML who were diagnosed from 2004 – 2020; their analysis excluded those with acute promyelocytic leukemia, as well as secondary-, treatment-related and Down syndrome-related AML. Patient diagnostic bone marrow and peripheral blood samples from key timepoints were collected and reviewed.

Patients were designated to alternative response groups, using combinations of 5% bone marrow blasts and 3 different thresholds for both ANC (250, 500 and 1000 mcL) and platelets (20,000, 50,000 and 80,000 mcL). Antoniou and colleagues compared survival and outcomes of the stratified response groups to that of current, established complete remission criteria.

Among the observed patient population, median age at diagnosis was 8.4 years old. Overall survival was 79.4% among patients; event-free survival (EFS) was 61.2%. Patients achieving complete remission with hematological regeneration—defined as ANC >1000 mcL and platelets >80,000 mcL) showed a similar outcome to that of those achieving ANC >500 mcL; platelets >50,000 mCL or ANC >200 mcL and platelets >20,000; or “no blasts” plus platelets >20,000 mcL.

The lone group to report an inferior EFS score (51.3%) was patients with >5% blasts following first induction (P <.01). As such, investigators believe there is no justification of postponing second adjustment in eligible pediatric patients.

“According to the centrally reviewed response data provided by the AML-BFM study group, the former complete remission definition in pediatric AML needs to be revised,” they concluded. “Our results suggest that the Cheson criteria in AML should be omitted and replaced by a definition complete remission with ≥ 5% blasts.”

The study, “Revision of Complete Remission Criteria in Pediatric AML,” was presented at ASH 2022.