Zusammenfassung
Diagnostik und Therapie | Die akute myeloische Leukämie (AML) kann anhand ihres Profils an Driver-Mutationen in 9 bis 11 pathogenetisch unterschiedliche Subgruppen differenziert werden. In der klinischen Routine werden NPM1, cEBPa und FLT3-ITD bestimmt. Neben der prognostischen Information solcher Bestimmungen können manche Marker auch für das Verlaufsmonitoring (MRD) genutzt werden.
Kurative Therapie | Die intensive aplasiogene Chemotherapie ist die Basis eines kurativen Therapiekonzeptes. Die Hinzunahme eines Genotyp-spezifischen Inhibitors hat bei der Subgruppe der FLT3-mutierten AML erstmals zu einer moderaten, aber signifikanten Verbesserung des Überlebens geführt. Nach Erreichen einer kompletten Remission erfolgt bei einem hohen Rezidivrisiko eine konsolidierende allogene Transplantation.
Palliative Therapie | Der bisherige Therapiestandard mit niedrig dosiertem Cytarabin ist durch die hypomethylierenden Substanzen Azacytidin und Decitabine abgelöst worden. Es werden mediane Überlebenszeiten von 8 bis 10 Monaten erreicht.
Kurative Therapie der Akuten Promyelozyten-Leukämie (APL) | Die APL ist zu der AML-Subgruppe mit der besten Prognose geworden. Ausdifferenzierende Substanzen wie ATRA und Apoptose-induzierende wie Arsentrioxid können in einer Chemotherapie-freien Kombination bei Niedrigrisiko-APL eine Heilungsrate von über 90 % erreichen.
Abstract
Acute myeloid leukemia (AML) has been genetically characterized extensively and can now be subdivided into 9 to 11 pathogenetically different subtypes according to their profile of driver mutations. In clinical practice karyotyping and molecular analysis of NPM1, cEBPa and FLT3-ITD are required for treatment stratification and potentially genotype specific treatment. Some markers such as NPM1 not only offer prognostic information but can also serve as markers of minimal residual disease and thus have the potential to guide therapy in the future.
The basis of curative treatment is intensive combination chemotherapy comprizing cytarabine and an anthracycline (”7 + 3” regimen). The prolonged duration of aplasia can be reduced significantly by accelerated therapy (“S-HAM” regimen). Following achievement of a complete remission patients with a low risk of relapse – based on genetic and clinical features – receive chemotherapy based consolidation therapy whereas high risk patients – and potentially also those with an intermediate risk – receive an allogeneic stem cell transplantation. Whereas adding the rather unspecific tyrosinekinase inhibitor sorafenib to standard treatment in unselected AML patients has not improved overall survival (OS), the addition of midostaurin to standard therapy in the selected group FLT3 mutated patients has resulted in a moderate but significant OS benefit.
Real world data show that in patients below 50 years a cure rate of ca. 50 % can be achieved. However less than 10 % of patients above the age of 70 will be alive after five years even after intensive treatment. Therefore when curative and intensive treatment is deemed impossible the therapeutic standard in elderly and unfit patients used to be low-dose cytarabine with an average OS of 4 months. This has now been replaced by a new standard of care of hypomethylating agents – azacytidine and decitabine – which both achieve higher remission rates and show strong trends towards a prolonged OS of between 8 and 10 months.
The paradigm for genotype-specific therapy is acute promyelocytic leukemia (APL – or AML M3 in the former FAB classification). This entity used to be a problematic AML subgroup because of its frequent coagulation disturbances and potentially fatal bleeding problems. Today patients with APL can be treated with a chemotherapy free combination of ATRA – a differentiating agent – and Arsenic Trioxide – an apoptosis inducing agent. In patients with a leukocyte count < 10 000 / µl a cure rate of > 90 % can now be achieved.
Schlüsselwörter
Leukämie - Therapie - Diagnostik - Transplantation - Genotyp
Keywords
Leukemia - therapy - diagnostics - transplantation - genotype
