Radioimmunotherapy for treatment of acute myeloid leukaemia and myelodysplastic syndrome

Summary

The prognosis of patients with acute myeloid leukaemia (AML) has improved considerably by introduction of aggressive consolidation chemotherapy and haematopoietic stem cell transplantation (SCT). Nevertheless, only 20-30% of patients with AML achieve long-term diseasefree survival after SCT. The most common cause of treatment failure is relapse. Additionally, mortality rates are significantly increased by therapy-related causes such as toxicity of chemotherapy and complications of SCT. Including radioimmunotherapies in the treatment of AML and myelodyplastic syndrome (MDS) allows for the achievement of a pronounced antileukaemic effect for the reduction of relapse rates on the one hand. On the other hand, no increase of acute toxicity and later complications should be induced. These effects are important for the primary reduction of tumour cells as well as for the myeloablative conditioning before SCT.

This paper provides a systematic and critical review of the currently used radionuclides and immunoconjugates for the treatment of AML and MDS and summarizes the literature on primary tumour cell reductive radioimmunotherapies on the one hand and conditioning radioimmunotherapies before SCT on the other hand.

Zusammenfassung

Die Prognose von Patienten mit akuter myeloischer Leukämie (AML) hat sich durch die Einführung aggressiver, konsolidierender Chemotherapien und der hämatopoietischen Stammzelltransplantation (SZT) wesentlich verbessert. Dennoch erreichen selbst nach Durchführung einer SZT nur 20-30% der Patienten mit AML ein langfristiges, krankheitsfreies Überleben. Die Hauptursache für das langfristige Therapieversagen ist das Rezidiv; doch auch die Toxizität der Chemotherapie und die Komplikationen der hämatopoietischen SZT beeinflussen die Mortalitätsrate signifikant. Sowohl im Kontext der primär tumorzellreduktiven Therapie als auch im Rahmen der Konditionierungstherapie vor SZT ist das wesentliche Therapieziel daher, einen ausgeprägten antileukämischen Effekt zur Reduktion der Rezidivrate zu erzeugen, ohne dabei die akute Toxizität und die spätere Komplikationsrate zu steigern.

Die Einbeziehung von Radioimmuntherapien in die Behandlungsstrategie bei der AML und beim myelodysplastischen Syndrom (MDS) ermöglicht die Applikation hoher spezifischer Dosen im hämatopoetischen Knochenmark und erzielt daher in hohem Maße den geforderten antileukämischen Effekt zur Reduktion der Rezidivrate. Durch die vergleichsweise geringe Dosis extramedullärer Organe und Gewebe bleibt die extramedulläre Toxizität gering.

Diese Übersicht stellt systematisch und kritisch wertend die aktuell eingesetzten Radionuklide und Immunkonjugate zur Behandlung der AML und des MDS vor und fasst den aktuellen Stand der Forschung zur primären Reduktion der leukämischen Blastenzahl einerseits sowie zur Konditionierung vor SZT andererseits zusammen.

Keywords

Radioimmuntherapy - haematology - leukaemia - transplantation

Schlüsselwörter

Radioimmuntherapie - Hämatologie - Leukämie - Transplantation

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