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Stem Cell Transplantation
Association of uric acid levels before start of conditioning with mortality after allogeneic hematopoietic stem cell transplantation – a prospective, non-interventional study of the EBMT Transplant Complication Working Party
1Charité Universitätsmedizin Berlin, Berlin, Germany; 2EBMT Statistical Unit, Paris, France; 3EBMT Data Office, Leiden, the Netherlands; 4University of Freiburg, Freiburg, Germany; 5Hannover Medical School, Hannover, Germany; 6Department of Hematology, University Hospital Leuven and KU Leuven, Leuven, Belgium; 7Imperial College, London, UK; 8HUCH Comprehensive Cancer Center, Helsinki, Finland; 9Antwerp University Hospital, Antwerp, Belgium; 10Erciyes University Medical Faculty, Kayseri, Turkey; 11Radboud University – Nijmegen Medical Centre, Nijmegen, the Netherlands; 12Hospital Santa Creu I Sant Pau, Barcelona, Spain; 13Fondazione IRCCS – Ca’Granda, Milan, Italy; 14Universitätsklinikum Göttingen, Göttingen, Germany; 15CHRU Limoges, Limoges, France; 16Hospital Clinic, Barcelona, Spain; 17Gazi University Faculty of Medicine, Ankara, Turkey; 18Hospital Regional de Málaga, Malaga, Spain; 19Instituto National do Cancer, Rio de Janeiro, Brazil; 20Elisabethinen-Hospital, Linz, Austria; 21LKH – University Hospital Graz, Graz, Austria; 22Hospital Universitario Puerta de Hierro, Madrid, Spain and 23Medical University of Warsaw, Warsaw, Poland
#RFD and GWB contributed equally as co-senior authors.
ABSTRACT
Uric acid is a danger signal contributing to inflammation. Its relevance to allogeneic stem cell transplantation (alloSCT) derives from preclin- ical models where the depletion of uric acid led to improved survival and reduced graft-versus-host disease (GvHD). In a clinical pilot trial, peri- transplant uric acid depletion reduced acute GvHD incidence. This prospec- tive international multicenter study aimed to investigate the association of uric acid serum levels before start of conditioning with alloSCT outcome. We included patients with acute leukemia, lymphoma or myelodysplastic syndrome receiving a first matched sibling alloSCT from peripheral blood, regardless of conditioning. We compared outcomes between patients with high and low uric acid levels with univariate- and multivariate analysis using a cause-specific Cox model. Twenty centers from 10 countries reported data on 366 alloSCT recipients. There were no significant differences in terms of baseline co-morbidity and disease stage between the high- and low uric acid group. Patients with uric acid levels above median measured before start of conditioning did not significantly differ from the remaining in terms of acute GvHD grades II-IV incidence (Hazard ratio [HR] 1.5, 95% Confidence inter- val [CI]: 1.0-2.4, P=0.08). However, they had significantly shorter overall sur- vival (HR 2.8, 95% CI: 1.7-4.7, P<0.0001) and progression free survival (HR 1.6, 95% CI: 1.1-2.4, P=0.025). Non-relapse mortality was significantly increased in alloSCT recipients with high uric acid levels (HR 2.7, 95% CI: 1.4-5.0, P=0.003). Finally, the incidence of relapse after alloSCT was increased in patients with higher uric acid levels (HR 1.6, 95% CI: 1.0-2.5, P=0.04). We conclude that high uric acid levels before the start of condition- ing correlate with increased mortality after alloSCT.
Ferrata Storti Foundation
Olaf Penack,1 Christophe Peczynski,2 Steffie van der Werf,3 Jürgen Finke,4
Arnold Ganser,5 Helene Schoemans,6 Jiri Pavlu,7 Riitta Niittyvuopio,8
Wilfried Schroyens,9 Leylagül Kaynar,10 Igor W. Blau,1 Walter van der Velden,11 Haematologica 2020 Jorge Sierra,12 Agostino Cortelezzi,13 Gerald Wulf,14 Pascal Turlure,15
Montserat Rovira,16 Zubeydenur Ozkurt,17 Maria J. Pascual-Cascon,18
Maria C. Moreira,19 Johannes Clausen,20 Hildegard Greinix,21
Rafael F. Duarte22# and Grzegorz W. Basak23#
Volume 105(7):1977-1983
Correspondence:
OLAF PENACK
olaf.penack@charite.de
Received: June 4, 2019. Accepted: October 4, 2019. Pre-published: October 10, 2019.
doi:10.3324/haematol.2019.228668
Check the online version for the most updated information on this article, online supplements, and information on authorship & disclosures: www.haematologica.org/content/105/7/1977
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