Prognosis and management of acute myeloid leukemia in patients with Down syndrome

Abstract

Children with Down syndrome (DS) are at a substantially increased risk to develop acute myeloid leukemia (AML). This increase in incidence is tempered, however, by favorable overall survival rates of approximately 80%, whereas survival for non-DS children with similar leukemic subtypes is <35%. In this review, the clinical studies that have contributed to this overall high survival will be presented and their individual successes will be discussed. Important issues including intensity of treatment regimens, the role of bone marrow transplants and prognostic indicators will be reviewed. In particular, the roles of high- vs low- vs very low-dose cytarabine will be discussed, as well as potential therapeutic options in the future and the direction of the field over the next 5 years. In summary, children with DS and AML should be treated with a moderate-intensity cytarabine-based regimen with curative intent.

Keywords::

• acute myeloid leukemia
• Down syndrome
• GATA1
• prognosis
• treatment

Financial & competing interests disclosure

The authors were supported by grants from the National Cancer Institute (R01 CA120772) and the Ring Screw Textron Endowed Chair for Pediatric Cancer Research. JT Caldwell is a predoctoral trainee supported by T32 CA009531 from the National Cancer Institute. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Children with Down syndrome (DS) are at substantially increased risk to develop acute myeloid leukemia, especially of the megakaryocytic subtype.

• Myeloid leukemias of Down syndrome (ML-DS) is a unique disease that has relatively excellent survival rates.

• Historic treatment failures were largely the result of undertreatment.

• As more ML-DS patients were treated on protocol, survival increased.

• Survival rates after relapse or in the context of refractory disease are dismal, even after bone marrow transplant.

• The efficacy of low-dose amount of active cytarabine is unclear; however, low-dose protocols may be useful in those for whom higher-dose therapy is contraindicated.

• Children with ML-DS should be treated on moderate-intensity protocols, preferably designed for ML-DS patients, with curative intent.