Recommendations for Diagnosis and Treatment of Children with Transient Abnormal Myelopoiesis (TAM) and Myeloid Leukemia in Down Syndrome (ML-DS)

Abstract

Children with Down syndrome are at a high risk of developing transient abnormal myelopoiesis (TAM; synonym: TMD) or myeloid leukemia (ML-DS). While most patients with TAM are asymptomatic and go into spontaneous remission without a need for therapy, around 20% of patients die within the first six months due to TAM-related complications. Another 20–30% of patients progress from TAM to ML-DS. ML-DS patients are particularly vulnerable to therapy-associated toxicity, but the prognosis of relapsed ML-DS is extremely poor – thus, ML-DS therapy schemata must strive for a balance between appropriate efficacy (to avoid relapses) and treatment-related toxicity. This guideline presents diagnostic and therapeutic strategies for TAM and ML-DS based on the experience and results of previous clinical studies from the BFM working group, which have helped reduce the risk of early death in symptomatic TAM patients using low-dose cytarabine, and which have achieved excellent cure rates for ML-DS using intensity-reduced treatment protocols.

Zusammenfassung

Kinder mit Down-Syndrom haben ein hohes Risiko, eine transiente abnorme Myelopoese (TAM; Synonym: TMD) oder myeloische Leukämie (ML-DS) zu entwickeln. Während die meisten Patienten mit TAM asymptomatisch bleiben und ohne Therapie eine Spontanremission erreichen, sterben ca. 20% der Patienten innerhalb der ersten sechs Monate an TAM-bedingten Komplikationen. Weitere 20–30% der Patienten zeigen einen Progress von TAM zu ML-DS. Patienten mit ML-DS sind besonders durch therapieassoziierte Toxizität gefährdet. Gleichzeitig ist die Prognose nach einem Rückfall sehr schlecht. Daher muss die Therapieintensität so gewählt werden, dass einerseits Rückfälle verhindert und andererseits therapiebedingte Komplikationen minimiert werden. Diese Richtlinie präsentiert diagnostische und therapeutische Maßnahmen für Patienten mit TAM und ML-DS, die auf den Erfahrungen und Ergebnissen früherer klinischer Studien der BFM-Arbeitsgruppe basieren, welche dazu beigetragen haben, das frühe Mortalitätsrisiko von symptomatischen TAM Patienten unter Einsatz von niedrig dosiertem Cytarabin zu reduzieren und mit intensitätsreduzierten Chemotherapieprotokollen hervorragende Heilungsraten für ML-DS Patienten zu erzielen.

Key words

down syndrome - trisomy 21 - leukemia - transient abnormal myelopoiesis - treatment recommendation - guideline

Schlüsselwörter

Down Syndrom - Trisomie 21 - Leukämie - transiente abnorme Myelopoese - Therapieempfehlung - Richtlinie

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