IntroductionChildhood acute myeloid leukemia (AML) is a rare and heterogeneous disease, with an incidence of 7 cases per million children younger than 15 years. In high-income countries, intensive therapy in conjunction with effective supportive care has increased survival rates to ϳ 70%. In 1990 and 2003, expert working groups made recommendations for diagnosis, outcomes, standardization of response criteria, and reporting standards for AML. 1,2 Recent improvements in identifying the molecular genetics and pathogenesis of AML have been implemented in the new World Health Organization (WHO) classification of AML. 3 These changes, and the definition of new diagnostic and prognostic markers and their associated targeted therapies, have prompted the update of earlier recommendations by an international group, on behalf of the European LeukemiaNet for AML in adults in 2010. 4 Despite broad overlap in the diagnostic and treatment recommendations for AML for children and adults, there are important differences in both the diagnostic criteria and disease management, which merit age-specific recommendations. The absence of published recommendations specific for pediatric AML motivated an international group of pediatric hematologists and oncologists (panel and participating groups see "Appendix") to develop evidence-and expert opinionbased consensus recommendations for the diagnosis and management of AML in children, incorporating emerging information on the biology of the disease. The scope of the review is presented in the "Appendix." Recommendations for specific subgroups are also included. This article discusses diagnostic procedures and initial workup, prognostic factors, response criteria, and management, and in particular focuses on differences between adults and children with AML. For personal use only. on May 12, 2018. by guest www.bloodjournal.org From WHO classification and pediatric AMLThe recent WHO 2008 classification is applicable to both adult and pediatric AML 3,5 and has been summarized by Döhner et al. 4 The classification contains most, but not all, cytogenetic subgroups specific to children. Differences in genetic background between children and adults are given in Table 1 and discussed further in "Cytogenetics."Compared with previous classifications (European Group of Immunologic Characterization of Leukemias [EGIL], WHO 2001), 6 the new WHO classification introduced a stringently defined subclass of acute leukemias of ambiguous lineage (mixed phenotype acute leukemias [MPALs]), mainly on the basis of detailed immunophenotypic criteria (Table 2) or presence of t(9;22)(q34; q11.2)/BCR-ABL1 or t(v;11q23)/MLL rearrangement. 3,5,6 The new classification aims to create uniform subgroups defined by unifying molecular targets, which allow selection of specific treatment. Diagnostic procedures and initial workupThe minimal diagnostic requirements in childhood AML are morphology with cytochemistry, immunophenotyping, karyotyping, FISH, and specific molecular genetics in the bone marrow, which is comparable ...

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Translocations involving chromosome 11q23 frequently occur in pediatric acute myeloid leukemia (AML) and are associated with poor prognosis. In most cases, the MLL gene is involved, and more than 50 translocation partners have been described. Clinical outcome data of the 11q23-rearranged subgroups are scarce because most 11q23 series are too small for meaningful analysis of subgroups, although some studies suggest that patients with t(9;11)(p22;q23) have a more favorable prognosis. We retrospectively collected outcome data of 756 children with 11q23-or MLL-rearranged AML from 11 collaborative groups to identify differences in outcome based on translocation partners. All karyotypes were centrally reviewed before assigning patients to subgroups. The event-free survival of 11q23/ MLL-rearranged pediatric AML at 5 years from diagnosis was 44% (؎ 5%), with large differences across subgroups (11% ؎ 5% to 92% ؎ 5%). Multivariate analysis identified the following subgroups as independent prognostic predictors: t(1;11)(q21;q23) (hazard ratio [HR] ‫؍‬ 0.1, P ‫؍‬ .004); t(6; 11)(q27;q23) (HR ‫؍‬ 2.2, P < .001); t(10; 11)(p12;q23) (HR ‫؍‬ 1.5, P ‫؍‬ .005); and t(10;11)(p11.2;q23) (HR ‫؍‬ 2.5, P ‫؍‬ .005). We could not confirm the favorable prognosis of the t(9;11)(p22;q23) subgroup. We identified large differences in outcome within 11q23/MLL-rearranged pediatric AML and novel subgroups based on translocation partners that independently predict clinical outcome. Screening for these translocation partners is needed for accurate treatment stratification at diagnosis. (Blood. 2009;114:2489-2496)

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Diagnosis, treatment, response monitoring, and outcome of pediatric acute myeloid leukemia (AML) have made enormous progress during the past decades. Because AML is a rare type of childhood cancer, with an incidence of approximately seven occurrences per 1 million children annually, national and international collaborative efforts have evolved. This overview describes these efforts and includes a summary of the history and contributions of each of the main collaborative pediatric AML groups worldwide. The focus is on translational and clinical research, which includes past, current, and future clinical trials. Separate sections concern acute promyelocytic leukemia, myeloid leukemia of Down syndrome, and relapsed AML. A plethora of novel antileukemic agents that have emerged, including new classes of drugs, are summarized as well. Finally, an important aspect of the treatment of pediatric AML--supportive care--and late effects are discussed. The future is bright, with a wide range of emerging innovative therapies and with more and more international collaboration that ultimately aim to cure all children with AML, with fewer adverse effects and without late effects.