Dosisreduzierte Konditionierung vor allogener Stammzelltransplantation

Hintergrund und Fragestellung: In der Leukämiebehandlung mit Stammzelltransplantation spielt der immunologische Effekt der allogenen T-Lymphozyten vermutlich eine größere Rolle als die hochdosierte Ganzkörperbestrahlung und Chemotherapie. Unter Ausnützung dieses Immuneffektes wird gegenwärtig versucht, die Dosis stammzell-toxischer Vorbehandlung wie der Ganzkörperbestrahlung zu reduzieren und damit die Transplantation einem größeren Kreis von Patienten mit hohem Transplantationsrisiko zugänglich zu machen. In der vorliegenden Arbeit werden drei laufende Studien zu diesem Ansatz bei verschiedenen Krankheitsentitäten vorgestellt.

Patienten und Methodik: Ältere Patienten mit chronischer myeloischer Leukämie haben ein erhöhtes Transplantationsrisiko und werden mit einer stufenweise reduzierten Ganzkörperbestrahlung konditioniert (n = 27). Fortgeschrittene und therapierefraktäre myeloische Leukämien werden mit Chemotherapie und dosisreduzierter Bestrahlung konditioniert (FLAMSA-Protokoll: n = 54); beim multiplen Myelom ermöglicht die autologe Transplantation mit hochdosierter Chemotherapie die spätere allogene Transplantation nach reduzierter Vorbehandlung (Tandem-Protokoll, n = 6).

Ergebnisse: Die Reduktion der Ganzkörperbestrahlung war bei allen drei Protokollen im historischen Vergleich nicht nachteilig. Bei der CML traten keine gehäuften Rezidive auf. Das FLAMSA-Protokoll erbrachte bei AML mit hohem Risiko ein günstiges Überleben. Die autolog-allogene Tandem-Transplantation wurde vergleichsweise gut vertragen und erbrachte ein Ansprechen bei allen Patienten.

Folgerung: Die allogene Transplantation nach dosisreduzierter Konditionierung eröffnet neue Möglichkeiten sowohl bezüglich der Ausweitung der Transplantationsindikation als auch bezüglich der Therapie bislang nur unbefriedigend zu behandelnder Erkrankungen.

Background and objective: In the treatment of leukemia by stem cell transplantation, the immunological effects of allogeneic T-lymphocytes presumably play a greater part than high-dosage total-body irradiation (TBI) and chemotherapy. Using this immunological effect, attempts are currently being made to reduce the dosage of pre-treatment that is toxic to stem cell, such as TBI, thereby making transplantation available for a larger group of patients at high risk for transplantation. This study presents preliminary results of three current studies of this approach.

Patients and methods: Elderly patients with chronic myeloid leukemia (CML) have an increased transplantation risk. They were conditioned with TBI that was reduced stepwise (n = 27). Patients with advanced and refractory myeloid leukemia were treated with chemotherapy and dose-reduced TBI (FLAMSA protocol; n = 54). In patients with multiple myeloma, autologous transplantation with high-dose chemotherapy preceded allogeneic transplantation possible after dose-reduced conditioning (Tandem protocol; n = 6).

Results: All three protocols of TBI gave results that were not worse than those of previous studies. Relapse ocurred not more frequently in patients with CML. In patients with high-risk AML the FLAMSA protocol gave better results. Autologous-allogeneic tandem transplantation was well tolerated and led to a good response in all patients.

Conclusion: Allogeneic transplantation after dose-reduced conditioning opens up new possibilities with respect to widening indications for transplantation and improving results in hematological diseases with previously unsatisfactory treatment.

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