Overview
Refractory acute myeloid leukemia (AML) refers to disease that does not respond to initial therapy or relapses after treatment. The prognosis for relapsed or refractory myeloid leukemia in children with Down syndrome (r/r ML-DS) is dire, with no established standard treatment 1. NCCN Guidelines provide recommendations for diagnosis and treatment of adults with AML, incorporating recent advances 2.Diagnosis
NCCN Guidelines for AML in adults incorporate familial genetic alterations and factors with prognostic importance for diagnosis and treatment decision-making 2.Management
For relapsed or refractory myeloid leukemia in children with Down syndrome (r/r ML-DS):
* Azacytidine (AZA) ± panobinostat for cases with low blast count 1.
* Fludarabine and cytarabine (FLA) ± gemtuzumab ozogamicin (GO) for cases with high blast count 1.
* Hematopoietic stem cell transplantation (HSCT) after achieving remission 1.
NCCN Guidelines for adults with AML include principles for venetoclax-based therapies and postinduction or postremission treatment strategies 2.Special Populations
Children with Down syndrome: Specific treatment recommendations exist for relapsed or refractory myeloid leukemia in this population, including AZA ± panobinostat, FLA ± GO, and HSCT 1.
Adults: NCCN Guidelines provide recommendations for diagnosis and treatment of adults with AML 2.
Patients preferring no blood transfusions: Considerations for these patients are included in NCCN Guidelines for AML 2.Key Recommendations
For children with Down syndrome and relapsed or refractory myeloid leukemia, consider azacytidine ± panobinostat for low blast count disease 1. (Evidence: Expert opinion)
For children with Down syndrome and relapsed or refractory myeloid leukemia, consider fludarabine and cytarabine ± gemtuzumab ozogamicin for high blast count disease 1. (Evidence: Expert opinion)
Hematopoietic stem cell transplantation is recommended after remission for children with Down syndrome and relapsed or refractory myeloid leukemia 1. (Evidence: Expert opinion)
NCCN Guidelines for adult AML incorporate principles for venetoclax-based therapies and postinduction/postremission strategies, based on clinical trials 2. (Evidence: Strong)References
1 Miladinovic M, Reinhardt D, Hasle H, Goemans BF, Tomizawa D, Hitzler J et al.. Guideline for treating relapsed or refractory myeloid leukemia in children with Down syndrome. Pediatric blood & cancer 2024. link
2 Pollyea DA, Bixby D, Perl A, Bhatt VR, Altman JK, Appelbaum FR et al.. NCCN Guidelines Insights: Acute Myeloid Leukemia, Version 2.2021. Journal of the National Comprehensive Cancer Network : JNCCN 2021. link