Prognostische Relevanz genetischer Aberrationen der akuten myeloischen Leukämie bei Kindern und Jugendlichen

Zusammenfassung

Die Prognose für Kinder und Jugendlichen mit akuter myeloischer Leukämie konnte durch zunehmend intensivere Therapieprotokolle der AML-BFM-Studiengruppe deutlich verbessert werden. Voraussetzung ist neben einer guten Supportivtherapie zur Prävention und Beherrschung von Komplikationen eine risikoadaptierte Therapie. In Deutschland wurden zwischen 1998 und 2010 912 Kinder und Jugendliche als Protokollpatienten in die AML-BFM-Studien 98 (n=413) und 2004 (n=499) eingeschlossen. Das 5-Jahre-ereignisfrei (EFS) und Gesamtüberleben (OS) beträgt 57±2% bzw. 71±2%. Während in den früheren Studien Zellzahl, Zytomorphologie und Zytochemie eingesetzt wurden, konnten in den letzten Jahren in der Zyto- und Molekulargenetik zunehmend relevante Prognosefaktoren identifiziert werden. Die Gruppe mit relativ günstiger Prognose umfasst die AML mit t(8;21), inv(16), t(15;17), t(1;11) sowie mit normalem Karyotyp und NPM1-Mutation (n=253; EFS 74±3%, OS 88±2%). Eine schlechte Prognose haben AML mit t(4;11), t(5;11), t(6;11), t(10;11); t(6;9), t(7;12), t(9;22), Monosomie 7, kombinierte FLT3-ITD/WT1-Mutationen, der(12p)-Aberration und AML mit komplexem Karyotyp (n=101; EFS 30±6%; OS 56±5%). Die Gruppe mit intermediärer Prognose (IR) umfasst alle anderen Subgruppen, insbesondere AML mit normalem Karyotyp, FLT3-ITD oder t(9;11) (n=558; EFS 43±2%; OS 64±2%). Für die Wahl der adäquaten Therapie muss in jedem Fall das Therapieansprechen berücksichtigt werden. Schlussfolgerung: Die Definition der genetischen Prognosefaktoren der AML bei Kindern ermöglicht eine verbesserte prognostische Einschätzung und bildet neben dem Therapieansprechen die Grundlage für Therapieempfehlungen.

Abstract

The survival rate of children and adolescents suffering acute myeloid leukemia (AML) has been significantly improved within the last decades. This has been achieved by a continuously intensified therapy and progress in supportive care to prevent and treat complications. In Germany, the AML-BFM trials 98 (n=413) and 2004 (n=499) enrolled 912 children and adolescents as protocol patients (1998–2010). The 5-year-overall survival was 71±2%. In the previous studies prognosis and subsequent treatment stratification based on morphology, cytochemistry and white blood cell count. Today, the identification of new genetic aberrations in AML enables a genetically determined estimation of prognosis, although treatment response must be considered for treatment stratification. The group with a favorable prognosis summarized AML with t(8;21), inv(16), t(15;17), t(1;11), and AML with normal karyotype and NPM1-mutation (n=253; EFS 74±3%, OS 88±2%). A poor prognosis (HR-group) must be expected in AML with t(4;11), t(5;11), t(6;11), t(6;9), t(7;12), t(9;22), Monosomy 7, combined FLT3/WT1-mutation, and AML with der(12p)-aberration (n=101; EFS 30±5%; OS 56±5%). The intermediate group summarizes all other subgroups especially AML with normal karyotyp, AML with FLT3-ITD or t(9;11) (n=558; EFS 43±2%; OS 64±2%). The validation of the internationally identified, genetically determined prognostic factors within the AML-BFM (Germany) study population will support treatment recommendations.

Schlüsselwörter

akute myeloische Leukämie - Kinder - Prognosefaktoren - Genetik

Key words

acute myeloid leukemia - childhood - prognostic factor - genetics

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