Outcomes of intensification of induction chemotherapy for children with high-risk acute myeloid leukemia: A report from the Children's Oncology Group.

TitleOutcomes of intensification of induction chemotherapy for children with high-risk acute myeloid leukemia: A report from the Children's Oncology Group.
Publication TypeJournal Article
Year of Publication2021
AuthorsElgarten CW, Wood AC, Li Y, Alonzo TA, Brodersen LEidenschin, Gerbing RB, Getz KD, Huang Y-SVera, Loken M, Meshinchi S, Pollard JA, Sung L, Woods WG, E Kolb A, Gamis AS, Aplenc R
JournalPediatr Blood Cancer
Paginatione29281
Date Published2021 Oct 01
ISSN1545-5017
Abstract

BACKGROUND: High-risk pediatric acute myeloid leukemia confers a poor prognosis, and alternative strategies are needed to improve outcomes. We hypothesized that intensifying induction on the AAML1031 clinical trial would improve outcomes compared to the predecessor trial AAML0531.

METHODS: Patients on AAML0531 received cytarabine (1600 mg/m )/daunorubicin (150 mg/m )/etoposide (ADE) for induction II and patients on AAML1031 received mitoxantrone (48 mg/m )/cytarabine (8000 mg/m ) (MA). Stem cell transplant (SCT) conditioning included busulfan/cyclophosphamide on AAML0531, whereas AAML1031 used busulfan/fludarabine and liberalized donor eligibility. Patients were included in this analysis if they met high-risk criteria common to the two trials by cytogenics or poor disease response after induction I ADE.

RESULTS: MA provided no benefit over ADE at: induction II response (complete response [CR]: 64% vs. 62%, p = .87; measurable residual disease [MRD]+: 57% vs. 46%, p = .34); or intensification I response (CR: 79% vs. 94%, p = .27; MRD+: 27% vs. 20%, p = 1.0). When considered with altered SCT approach, MA did not improve 5-year disease-free survival (24% ± 9% vs. 18% ± 15%, p = .63) or 5-year overall survival (35% ± 10% vs. 38% ± 18%, p = .66). MA was associated with slower neutrophil recovery (median 34 vs. 27 days, p = .007) and platelet recovery (median 29 vs. 24.5 days, p = .04) and longer hospital stay (32 vs. 28 days, p = .01) during induction II.

CONCLUSION: Intensification of induction II did not improve treatment response or survival, but did increase toxicity and resource utilization. Alternative strategies are urgently needed to improve outcomes for pediatric patients with high-risk acute myeloid leukemia (trials registered at clinicaltrials.gov NCT01371981, NCT00372593).

DOI10.1002/pbc.29281
Alternate JournalPediatr Blood Cancer
PubMed ID34596937
Grant ListCOG NCTN Network Group Operations Centres (5U10CA180886-07) / / Division of Cancer Prevention, National Cancer Institute /
(2U10CA180899-07). / / NCTN Statistics & Data Center Grant /