**3. Conclusion**

APL is a distinct subtype of AML and is characterized by t(15;17). This translocation involves a breakpoint that includes the retinoic acid receptor and leads to production of the promyelocytic leukemia (PML)-retinoic acid receptor alpha (RARA) fusion protein [96]. Treatment is usually begun immediately with all-trans retinoid acid (ATRA) as APL is associated with an increased risk of a life threatening hemorrhage. In children, a dose of

Arsenic trioxide has proven to be an effective agent in combination with ATRA in the treatment of newly diagnosed, refractory, or relapsed APL [77]. In patients with hyperleukocytosis treated with ATRA or arsenic trioxide, approximately 10% of children can develop APL differentiation syndrome. This syndrome is characterized by fever, weight gain, respiratory distress, pleural, and pericardial effusions. The incidence of APL differentiation syndrome can be reduced by combining ATRA with chemotherapy. Pseudotumor cerebri occurs in 11% of children during initial ATRA administration and can be treated

Although there have been major improvements in treatment outcomes, AML remains a life-threatening malignancy. Approximately, 30% of pediatric patients relapse, with only 30–40% of these relapsed patients surviving, indicating a poor outcome [101, 102]. AML is a highly heterogeneous disease and through gaining knowledge on its molecular and genetic background it will allow new targeted and patient-specific therapies to become available to

The estimated incidence in children with high-risk AML of severe bacterial infections is 50–60% and the estimated incidence of invasive fungal infections is 7.0–12.5% [103–105]. The improved outcome in children with AML over the last 10 years may be associated to better

Hyperleukocytosis (WBC greater than 100,000/μL) at initial diagnosis is associated with an increased risk of CNS hemorrhage and leukostasis. Patients with monocytic or myelomonocytic (FAB M4 and M5) as well as APL and hyperleukocytosis are at an increased risk of early death [106, 107]. Treatment involves emergency care with intensive monitoring and careful hydration with the addition of rasburicase [108]. In more severe cases involving symptomatic coagulopathy, exchange transfusion or leukapheresis may be required. Controlled and effective reduction in cells with enforced diuresis or hemodialysis, may prevent the occurrence of

Hematopoietic growth factors such as granulocyte-macrophage colony-stimulating factor (GM-CSF) or granulocyte colony-stimulating factor (G-CSF) during AML induction therapy are not recommended in the pediatric population. Although a randomized study in children with AML evaluated G-CSF administered after induction chemotherapy showed a reduction in duration of neutropenia there was no difference in infectious complications or mortality [109]. In addition, a higher relapse rate has been recently demonstrated

per day of ATRA should be started and has shown to produce equivalent out-

per day that is commonly used in adults [97–99].

25 mg/m2

30 Myeloid Leukemia

children.

with steroids [97, 100].

**2.5. Supportive treatment**

supportive care strategies.

tumor lysis syndrome [106–108].

comes to the higher dose of 45 mg/m2

The diagnosis and treatment of AML has significantly improved over the past decades. Risk stratification has allowed for more targeted and specific therapy while avoiding, over treatment in low-risk patients and allowing for more intensive therapy in others. AML is a highly heterogeneous disease and through gaining knowledge on its molecular and genetic background as well as international collaboration, it will allow new targeted and patient-specific therapies to become available, particularly in pediatric patients.
