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DOI: 10.1055/s-2005-916351
© Georg Thieme Verlag Stuttgart · New York
Allogene Blutstammzelltransplantation von Risikopatienten nach Konditionierung mit Treosulfan und Fludarabin
Allogeneic blood stem cell transplantation of high-risk patients after conditioning with treosulfan and fludarabinePublication History
eingereicht: 16.6.2005
akzeptiert: 25.8.2005
Publication Date:
20 September 2005 (online)
![](https://www.thieme-connect.de/media/dmw/200538/lookinside/thumbnails/10.1055-s-2005-916351-1.jpg)
Zusammenfassung
Hintergrund und Fragestellung: Viele Patienten mit hämatologischen Erkrankungen müssen von einer allogenen Transplantation aufgrund drohender Nebenwirkungen der Konditionierung ausgeschlossen werden. Dosisreduzierte Verfahren umgehen zwar dieses Problem, können aber Effektivität einbüßen. Wir haben deshalb ein dosisintensives, aber toxizitätsreduziertes Konditionierungsverfahren mit Treosulfan und Fludarabin entwickelt und berichten über die ersten Erfahrungen.
Patienten und Methodik: Bei 65 Patienten mit einem medianen Alter von 50 Jahren erfolgte eine Blutstammzelltransplantation von verwandten (n = 21) oder unverwandten Spendern (n = 44) nach Konditionierung mit Treosulfan (3 × 10, 3 × 12 oder 3 × 14 g/m² i. v.) und Fludarabin (5 × 30 mg/m² i. v.). 21 Patienten waren zum Zeitpunkt der Transplantation in kompletter Remission (CR), 44 Patienten hatten keine CR erreicht. 59 der 65 Patienten waren für eine konventionelle Konditionierung nicht geeignet.
Ergebnisse: Die Gesamtüberlebensrate nach 3 Jahren (nach Kaplan-Meier) lag bei 59,2 %, das ereignisfreie Überleben bei 40,1 %. Patienten mit verwandtem Spender oder Transplantation in CR hatten eine deutlich bessere Gesamt- (85,4 % bzw. 74,2 %) und ereignisfreie Überlebensrate (52,2 % bzw. 61,9 %). Rezidive waren bei 26,2 % der Patienten nach 3 Jahren aufgetreten. Die transplantationsbedingte Mortalität an Tag 100 betrug 17,4 %. Die schrittweise Cox-Regressionsanalyse zeigte, dass bei unseren Patienten die Kovariablen Transplantation in CR vs. nicht in CR und der Spenderstatus einen signifikanten Einfluss auf das Gesamt- und ereignisfreie Überleben bzw. die transplantationsbedingte Mortalität hatten.
Folgerungen: Unsere Erfahrungen mit einer dosisintensiven Konditionierungstherapie mit Treosulfan und Fludarabin zeigen, dass auch bei Patienten höheren Alters, mit schweren Begleiterkrankungen oder nach intensiver Vorbehandlung eine Blutstammzelltransplantation erfolgreich und ohne erhöhte transplantationsbedingte Mortalität verlaufen kann.
Summary
Background and objective: Allogeneic transplantation can not be offered to many patients due to potential side-effects of conventional conditioning. Dose-reduced conditioning approaches improve tolerability, however, treatment efficacy may be reduced as well. We have, therefore, developed a dose intense but toxicity reduced conditioning regimen based on treosulfan and fludarabine and report first results.
Patients and methods: 65 patients with a median age of 50 years were transplanted from related (n = 21) or unrelated donors (n = 44) after conditioning with treosulfan (3 × 10, 3 × 12 or 3 × 14 g/m² i. v.) and fludarabine (5 × 30 mg/m² i. v.). 21 patients were in complete remission (CR) and 44 patients had not reached a CR at the time of transplantation. 59 of 65 patients were considered unfit for a conventional conditioning regimen.
Results: The actuarial overall survival after 3 years is 59.2 %, the event-free survival 40.1 %. Patients with a related donor or transplantation in CR had a better overall (85.4 resp. 74.2 %) and event-free survival (52.2 % resp. 61.9 %). The cumulative incidence of relapse at 3 years was 26.2 %. Non-relapse mortality at day 100 is 17.4 % (cumulative incidence). In stepwise Cox regression analyses for overall survival, event-free survival and non-relapse mortality the covariables transplantation in CR vs. not in CR and the donor status were shown to be influential.
Conclusions: These results with a conditioning therapy of treosulfan and fludarabine indicate that patients despite higher age, concomitant disease or after intensive pretreatment can be successfully transplanted without increased treatment-related mortality.
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Priv.-Doz. Dr. med. Jochen Casper
Abteilung Hämatologie und Onkologie, Klinik für Innere Medizin der Universität Rostock
Ernst-Heydemann-Straße 6
18057 Rostock
Phone: 0381/4947435
Fax: 0381/4947422
Email: jochen.casper@med.uni-rostock.de