Abstract
Myeloid leukemia in children with Down syndrome (ML-DS) is associated with young age and somatic GATA1 mutations. Because of high event-free survival (EFS) and hypersensitivity of the leukemic blasts to chemotherapy, the prior Children's Oncology Group protocol ML-DS protocol (AAML0431) reduced overall treatment intensity but lacking risk stratification, retained the high-dose cytarabine course (HD-AraC), which was highly associated with infectious morbidity. Despite high EFS of ML-DS, survival for those who relapse is rare. AAML1531 introduced therapeutic risk stratification based on the previously identified prognostic factor, measurable residual disease (MRD) at the end of the first induction course. Standard risk (SR) patients were identified by negative MRD using flow cytometry (<0.05%) and did not receive the historically administered HD-AraC course. Interim analysis of 114 SR patients revealed a 2-year EFS of 85.6% (95% confidence interval [CI], 75.7-95.5), which was significantly lower than for MRD- patients treated with HD-AraC on AAML0431 (P = .0002). Overall survival at 2 years was 91.0% (95% CI, 83.8-95.0). Twelve SR patients relapsed, mostly within 1 year from study entry and had a 1-year OS of 16.7% (95% CI, 2.7-41.3). Complex karyotypes were more frequent in SR patients who relapsed compared with those who did not (36% vs 9%; P = .0248). MRD by error-corrected sequencing of GATA1 mutations was piloted in 18 SR patients and detectable in 60% who relapsed vs 23% who did not (P = .2682). Patients with SR ML-DS had worse outcomes without HD-AraC after risk classification based on flow cytometric MRD.
Original language | English (US) |
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Pages (from-to) | 2337-2346 |
Number of pages | 10 |
Journal | Blood |
Volume | 138 |
Issue number | 23 |
DOIs | |
State | Published - Dec 9 2021 |
Bibliographical note
Funding Information:This work was supported by grants from the National Institutes of Health National Clinical Trials Network (NCTN) Operations Center, National Cancer Institute (U10CA180886), National Clinical Trials Network (NCTN) Statistics & Data Center (U10CA180899), and the St Baldrick's Foundation. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Funding Information:
The authors thank Vani Shanker for her constructive review of the manuscript. This work was supported by grants from the National Institutes of Health National Clinical Trials Network (NCTN) Operations Center, National Cancer Institute (U10CA180886), National Clinical Trials Network (NCTN) Statistics & Data Center (U10CA180899), and the St Baldrick's Foundation. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Publisher Copyright:
© 2021 American Society of Hematology
PubMed: MeSH publication types
- Research Support, Non-U.S. Gov't
- Journal Article
- Research Support, N.I.H., Extramural
- Clinical Trial