Der Onkologe

, Volume 11, Issue 9, pp 968–976 | Cite as

Experimentelle Therapie des Hodgkin-Lymphoms

Leitthema
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Zusammenfassung

Die hohen Heilungsraten von 85–95% in allen Stadien des Hodgkin-Lymphoms (HL) werden durch therapieassoziierte Komplikationen bedroht. So versterben Lanzeitüberlebende häufiger an Spättoxizitäten als an einem Rezidiv der Erkrankung. Es erscheint daher notwendig, neue, individualisierte Behandlungskonzepte zu entwickeln, die sich an der Biologie der Erkrankung orientieren. An erster Stelle steht die Definition von Risikogruppen, die eine schlechte Prognose haben und möglicherweise von einer weiteren initialen Therapieeskalation profitieren würden und von Risikogruppen, die eine gute Prognose haben und somit evtl. weniger aggressiv behandelt werden sollten. Biologische Faktoren (histologische Kriterien, serologische Marker oder genetische Polymorphismen) könnten in Kombination mit etablierten klinischen Faktoren die Basis eines neuen Risikoscores bilden. An zweiter Stelle steht die Entwicklung neuer Therapiemodalitäten, die gezielt spezifische molekulare Charakteristika des HL berücksichtigen. Dazu zählen immuntherapeutische Ansätze (Antikörper und zelluläre Vakzine) sowie niedrig molekulare Substanzen oder Antisense-Moleküle, die den proproliferativen und antiapoptotischen Phänotyp der Hodgkin- und Reed-Sternberg-Zellen auf molekularer Ebene angreifen. Bisherige klinische Phase-I/II-Studien zeigen allerdings lediglich einen geringen Effekt der genannten experimentellen Strategien, sodass weitere Entwicklungen unter Berücksichtigung individueller Risikofaktoren notwendig erscheinen.

Schlüsselwörter

Molekulare Therapie Niedrig molekulare Substanzen Antikörper Immuntherapie Risikostratifizierung 

Experimental therapy for Hodgkin lymphoma

Abstract

Although 85–95% of Hodgkin Lymphoma (HL) patients can be cured for all stages of the disease, high cure rates are threatened by acute and chronic therapy associated toxicities. Long term survivors of HL are more likely to die from late toxicities than from HL itself. It therefore seems to be necessary to develop novel biologically based therapies for HL. First, it is important to define selected risk groups in order to differentiate between good risk patients who might benefit from a de-escalation of therapy and high risk patients who could receive escalated treatment. Biological factors such as histological markers, serological factors or genomic polymorphisms in combination with established clinical risk factors might be the basis for these novel risk scores in the future. Second, it is crucial to identify transforming mechanisms in HL in order to develop novel therapeutic modalities that specifically target these events. Immunotherapeutic approaches (such as antibodies or cellular vaccines) and small molecules or antisense molecules might be suitable for targeting the pro-proliferative and anti-apoptotic phenotype of Hodgkin and Reed-Sternberg cells. Unfortunately, experimental phase I/II trials have so far showed only little clinical effect in relapsed HL patients. It therefore seems to be necessary to develop novel therapeutic strategies for HL patients based on the molecular characteristics of the malignant cells and individual risk factors.

Keywords

Targeted therapy Small molecules Antibodies Immunotherapy Risk stratification 

Notes

Interessenkonflikt:

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Copyright information

© Springer Medizin Verlag 2005

Authors and Affiliations

  1. 1.Klinik I für Innere Medizin, Universitätsklinik Köln
  2. 2.The Burnham Institute, John Reed LaboratoryLa JollaUSA
  3. 3.Klinik I für Innere Medizin, Universitätsklinik Köln

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