Treatment of acute myeloid leukemia in children: A practical perspective

Abstract

Pediatric acute myeloid leukemia (AML) is a heterogeneous disease that requires a multifaceted treatment approach. Although outcomes for low-risk AML have improved significantly over recent decades, high-risk AML continues to be associated with an adverse prognosis. Recent advances in molecular diagnostics, risk stratification, and supportive care have contributed to improvements in outcomes in pediatric AML. Targeted approaches, for example, the use of tyrosine kinase inhibitors to treat FLT3-ITD AML, offer promise and are currently undergoing clinical investigation in pediatric patients. New approaches to hematopoietic stem cell transplantation, including the use of haploidentical donors, are significantly expanding donor options for patients with high-risk AML. This review provides an overview of recent advances in the treatment of pediatric AML that are likely to have clinical impact and reshape the standard of care. K E Y W O R D Sacute myeloid leukemia, childhood AML, HSCT, pediatric AML Historically, risk stratification rested on blast morphology and cytogenetics. Improvement of cytogenetic techniques, flow cytometry, and introduction of molecular techniques, such as targeted sequencing and the detection of fusion transcripts, have identified a larger number of prognostic markers. 5 A summary is shown in Table 1. Mutations of uncertain prognostic significance in pediatric AML include point mutations targeting the c-KIT receptor tyrosine kinase and the FLT3

Development and validation of a prognostic scoring model to risk stratify childhood acute myeloid leukaemia

“…However, chemotherapy alone is still unsatisfactory in some patients, and these patients are often stratified into the high-risk group and are candidates for allogeneic haematopoietic stem cell transplantation (HSCT). 2 In addition, the intensity of chemotherapy should be tailored personally to maximise efficacy and minimise toxicity. Altogether, the treatment for AML requires precise and personal risk stratification.…”

“FLipping” the Story: FLT3-Mutated Acute Myeloid Leukemia and the Evolving Role of FLT3 Inhibitors

“…In most cases, the predominant AML clone is heterozygous for the FLT3 -ITD mutation, although subclones may be biallelic, hemizygous, possess a different specific mutation, or lack the FLT3 -ITD mutation altogether; such alterations also affect the AR [ 48 , 49 ]. It is unclear at which specific “threshold” the AR becomes deleterious, but higher ARs (e.g., a greater proportion of mutant-to-wild-type alleles) are correlated with an adverse prognosis [ 50 , 51 , 52 , 53 , 54 ]. Other studies have not shown a marked difference between high and low ARs [ 51 , 55 ], with patients with FLT3 -ITD mutations having poorer outcomes than those without FLT3 mutations, irrespective of the AR.…”

“…However, being relatively non-specific, sorafenib was poorly tolerated, and only 25% of children with FLT3 -ITD AML received maintenance sorafenib according to the study protocol; frequent dose modifications, dose holds, and drug discontinuation occurred [ 130 , 131 ]. Further, significant cardiotoxicity resulted in the study being temporarily paused [ 52 , 130 , 131 ].…”

Eltrombopag and its iron chelating properties in pediatric acute myeloid leukemia

“…The combined administration of cytarabine (Ara-C) and antracycline currently represents the principal therapeutic strategy for AML in pediatric patients, while for post-remission therapy repeated courses of high-dose Ara-C together with other cytotoxic agents are strongly indicated [ 3 ]. Also allogeneic hematopoietic stem cell transplantation (HSCT) is widely utilized to consolidate the state of remission [ 6 ], even though its actual benefits in comparison to conventionally used chemotherapy has been questioned in last years since the observed risk of relapse and late side effects. Although the amelioration of outcome for this pathology [ 7 ], stronger efforts to overcome the side effects related to standard therapy and also to ameliorate the life quality of patients are needed.…”