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Order of application and liver toxicity in patients given BU and CY containing conditioning regimens for allogeneic hematopoietic SCT

Cantoni, N. and Gerull, S. and Heim, D. and Halter, J. and Bucher, C. and Buser, A. and Tsakiris, D. A. and Passweg, J. and Tichelli, A. and Stern, M. and Gratwohl, A.. (2011) Order of application and liver toxicity in patients given BU and CY containing conditioning regimens for allogeneic hematopoietic SCT. Bone marrow transplantation, Vol. 46, H. 3. pp. 344-349.

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Official URL: http://edoc.unibas.ch/dok/A6003386

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Abstract

BU-CY is the established non-TBI-based myeloablative conditioning regimen for allogeneic hematopoietic SCT. However, liver toxicity and hepatic veno-occlusive disease (VOD) are frequent life-threatening complications. Pharmacological considerations suggest that BU can trigger toxicity of subsequent CY. Recent animal data confirmed this hypothesis. Less liver toxicity and better outcomes were observed when mice were treated with the reversed order of CY and BU. We analyzed in this study liver toxicity and outcome in patients receiving BU-CY (16 patients) or CY-BU (59 patients). Liver function differed significantly with higher levels of liver function tests between day +10 and +30, and a higher cumulative incidence of VOD in the BU-CY cohort (2/16 (12.5%) vs 0/59 (0%), P=0.006). TRM was significantly higher in patients receiving BU-CY (cumulative incidence BU-CY 45%, CY-BU 17%, P=0.02), without yet translating into a significant survival difference (incidence for survival: BU-CY 38%, CY-BU 63%; hazard ratio 1.19 for BU-CY, 95% confidence interval 0.29-4.82, P=0.80). Rates of engraftment and relapse were not different. These data support the concepts derived from animal models in favor of CY-BU compared with traditional BU-CY and form the basis for prospective controlled comparisons.
Faculties and Departments:03 Faculty of Medicine > Bereich Querschnittsfächer (Klinik) > Ehemalige Einheiten Querschnittsfächer (Klinik) > Hämostaselabor (Marbet)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Querschnittsfächer (Klinik) > Ehemalige Einheiten Querschnittsfächer (Klinik) > Hämostaselabor (Marbet)
03 Faculty of Medicine > Bereich Medizinische Fächer (Klinik) > Hämatologie > Hämatologie (Passweg)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Medizinische Fächer (Klinik) > Hämatologie > Hämatologie (Passweg)
03 Faculty of Medicine > Departement Biomedizin > Former Units at DBM > Immunotherapy (Stern)
UniBasel Contributors:Tsakiris, Dimitrios A. and Heim, Dominik A. and Stern, Martin Andreas and Passweg, Jakob R.
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Nature Publishing Group
ISSN:0268-3369
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:27 Mar 2014 13:13
Deposited On:27 Mar 2014 13:13

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