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Ruutu (Abstract)

Cellular Therapy and Transplantation (CTT), Vol. 2, No. 5, 2009
doi: 10.3205/ctt-2009-No5-abstract47
© The Author. This abstract is provided under the following license:
Creative Commons Attribution 3.0 Unported


Abstract accepted for "Joint EBMT Pediatric Working Party – 3rd Raisa Gorbacheva Memorial Meeting on Hematopoietic Stem Cell Transplantation", Saint Petersburg, Russia, September 17–20, 2009

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Reduced-toxicity conditioning in allogeneic stem cell transplantation for malignant hematological disorders

Tapani Ruutu

Division of Hematology, Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland

Correspondence: Tapani Ruutu, Division of Hematology, Department of Medicine, Helsinki University Central Hospital, PO Box 340, 00029 HUS, Helsinki, Finland, E-Mail: tapani.ruutu@hus.fi

Abstract

Allogeneic stem cell transplantation is an efficient treatment of malignant hematological disorders but considerable morbidity and mortality limit its use. To reduce complications, conditioning regimens with reduced extramedullary toxicity compared to standard regimens—but with a strong cytotoxic effect on hematopoietic cells—can be used. The combination of treosulfan (14 g/m2 x 3) and fludarabine (30 mg/m2 x 5) is such a regimen. It has been used in clinical studies as well as in routine practice in patients too fragile to be given conventional conditioning. In a phase II study in MDS, 45 patients were transplanted using this conditioning. The median age was 50 (range 22–63) years. Of the donors 33% were related and 67% unrelated (MUD). The IPSS risk groups were 7% low, 44% Int-1, 31% Int-2, and 18% high. GVHD prophylaxis was CsA+MTX, and ATG in case of MUD. The graft was PBPC in 89% and BM in 11%. The median follow-up was 25 (range 12–41) months. The median times to neutrophil (> 0.5 x 109/l) and platelet (> 20 x 109/l) engraftment were 18 and 17 days. The cumulative incidence (CI) of complete donor chimerism was 73% on day +28 and 93% on day +100. The toxicity was very modest. The CI of gr II–IV aGVHD was 24% and that of gr III–IV 16%. The CI of cGVHD at 2 years was 59% and that of extensive cGVHD 28%. The CI of non–relapse mortality was 9% at 100 days and 17% at 2 years, and that of relapse/progression 16% at 2 years. The Kaplan-Meier estimates of OS and DFS at 2 years were 71% and 67%. These data confirm the favourable safety and efficacy of treosulfan-based conditioning in MDS. Because of the modest toxicity, allogeneic transplantation using treosulfan-based conditioning can be offered to many patients considered too fragile to receive conventional conditioning.

Keywords: allogeneic stem cell transplantation, reduced-toxicity conditioning, myelodysplastic syndrome, treosulfan, fludarabine

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