Diagnosis and management of acute myeloid leukemia in children and adolescents: recommendations from an international expert panel

Abstract

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 ...

Outcome of children with high-risk acute myeloid leukemia given autologous or allogeneic hematopoietic cell transplantation in the aieop AML-2002/01 study.

“…10,25,26 The outcome of children transplanted from UDs acquires particular value in light of the fact that this type of allograft was employed in patients either with poor-prognosis molecular lesions, such as FLT3-ITD, or in infants, or in children with M7-AML or complex karyotype or in those patients not responding to the first course of induction therapy, these subgroups notoriously predicting a grim prognosis. 2,8,17,27,28 We and others have previously provided evidence that the outcome of children with acute lymphoblastic leukemia given HSCT from an UD has improved over time, 12,13,26 and the present results confirm that currently, thanks to the improvements in HLA typing obtained through the use of high-resolution molecular techniques and the optimization of GVHD prevention and treatment, post-transplantation outcome is not influenced by the type of donor used, either related or unrelated.…”

“…[33][34][35] The merits of using HSCT, in particular the autograft procedure, as consolidation therapy for pediatric patients with CR1 AML have been contested vigorously in the past years in light of the progress achieved with chemotherapy, and the risks inherent to the procedure have been advocated in support of restricting the use of transplantation. 2,4 Moreover, growing attention has been paid to the emergence of the potentially severe side effects, including also cGVHD, correlated to the transplant procedure. These considerations must certainly be put forward also in our cohort of patients, which, however, did not include any child with acute promyelocytic leukemia or core-binding factor anomalies.…”

“…5,7 Nowadays, large cooperative groups consider AML children with high-risk (HR) features, such as unfavorable cytogenetic/molecular characteristics or poor minimal residual disease clearance, eligible to be offered an allograft from an HLA-compatible sibling in CR1. 2,8 In the past few years, several studies have documented that transplantation of unrelated CB cells in children with CR1 AML is associated with a favorable outcome, particularly in patients aged less than 1 year at time of diagnosis. [9][10][11] The use of high-resolution molecular typing techniques for selecting an unrelated donor (UD) has also dramatically reduced the risk of immune-mediated complications and TRM, thus widening the indications for HSCT from an unrelated volunteer, which now are in part coincident with those for matched-related HSCT.…”

“…[1][2][3] Besides better risk stratification, use of repeated course of intensive consolidation therapy and amelioration of supportive therapy, a remarkable contribution to this improvement has been given by the wide use of hematopoietic SCT (HSCT). [4][5][6][7] In particular, for children achieving first CR1, allogeneic (ALLO) HSCT from an HLA-identical sibling has been shown to be the most effective post-remission therapy for preventing leukemia recurrence.…”

Effectiveness of supportive care measures to reduce infections in pediatric AML: a report from the Children’s Oncology Group

“…Furthermore, the rates of sterile-site fungal infection and NRM are low and thus, these analyses had limited power. Finally, other supportive care measures such as empiric antibiotics that provide coverage against virulent organisms in pediatric AML such as viridans group streptococci and gram-negative organisms such as P aeruginosa are also important, 22 and we did not include these aspects in our study.…”