title: Uric acid as a novel biomarker for bone-marrow function and incipient hematopoietic reconstitution after aplasia in patients with hematologic malignancies.
abstract: OBJECTIVE
  Prolonged aplasia and graft failure (GF) represent life-threatening complications after hematopoietic cell transplantation (HCT) requiring suitable biomarkers for early detection and differentiation between GF and poor graft function (PGF). Uric acid (UA) is a strong immunological danger signal.
  
  
  METHODS
  Laboratory results were analyzed from patients undergoing either allogeneic or autologous HCT or induction chemotherapy for acute leukemia (n = 50 per group, n = 150 total).
  
  
  RESULTS
  During therapy, UA levels declined from normal values to hypouricemic values (all p < 0.001). Alongside hematopoietic recovery, UA serum levels returned to baseline values. During aplasia, UA levels remained low and started steadily increasing (defined as >two consecutive days, median one 2-day increase) at a median of 1 day before rising leukocytes in allogeneic HCT (p = 0.01) and together with leukocytes in autologous HCT (median one 2-day increase). During induction chemotherapy, a UA increase was also observed alongside rising leukocytes/neutrophils but also several times during aplasia (median 3 increases). Most HCT patients had no detectable leukocytes during aplasia, while some leukocytes remained detectable after induction therapy. No increase in UA levels was observed without concomitant or subsequent rise of leukocytes.
  
  
  CONCLUSIONS
  Changes in UA serum levels can indicate incipient or remaining immunological activity after HCT or induction therapy. They may, therefore, help to differentiate between PGF and GF.
authors.affiliation: Medizinische Universitaetsklinik, Abteilung II fuer Onkologie, Haematologie, Immunologie, Rheumatologie und Pulmologie, Otfried Mueller Str. 10, 72076, Tuebingen, Germany. sebastian.haen@med.uni-tuebingen.de.|Interfakultaeres Institut fuer Zellbiologie, Abteilung Immunologie, Auf der Morgenstelle 15, 72076, Tuebingen, Germany. sebastian.haen@med.uni-tuebingen.de.
authors.forename: Sebastian P
authors.identifier: http://orcid.org/0000-0002-3655-4668
authors.initials: SP
authors.lastname: Haen
authors.affiliation: Medizinische Universitaetsklinik, Abteilung II fuer Onkologie, Haematologie, Immunologie, Rheumatologie und Pulmologie, Otfried Mueller Str. 10, 72076, Tuebingen, Germany.
authors.forename: Vicky
authors.initials: V
authors.lastname: Eyb
authors.affiliation: Medizinische Universitaetsklinik, Abteilung II fuer Onkologie, Haematologie, Immunologie, Rheumatologie und Pulmologie, Otfried Mueller Str. 10, 72076, Tuebingen, Germany.|Interfakultaeres Institut fuer Zellbiologie, Abteilung Immunologie, Auf der Morgenstelle 15, 72076, Tuebingen, Germany.
authors.forename: Nora
authors.initials: N
authors.lastname: Mirza
authors.affiliation: Institut fuer klinische Epidemiologie und angewandte Biometrie, Silcherstr. 5, 72076, Tuebingen, Germany.
authors.forename: Aline
authors.initials: A
authors.lastname: Naumann
authors.affiliation: Medizinische Universitaetsklinik, Abteilung IV fuer Endokrinologie, Diabetologie, Angiologie, Nephrologie und Klinische Chemie, Otfried Mueller Str. 10, 72076, Tuebingen, Germany.|Institute of Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Center Munich at the University of Tuebingen, Tuebingen, Germany.|German Center for Diabetes Research (DZD), Muenchen-Neuherberg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Peter
authors.affiliation: Interfakultaeres Institut fuer Zellbiologie, Abteilung Immunologie, Auf der Morgenstelle 15, 72076, Tuebingen, Germany.
authors.forename: Markus W
authors.initials: MW
authors.lastname: Löffler
authors.affiliation: Medizinische Universitaetsklinik, Abteilung II fuer Onkologie, Haematologie, Immunologie, Rheumatologie und Pulmologie, Otfried Mueller Str. 10, 72076, Tuebingen, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Faul
authors.affiliation: Medizinische Universitaetsklinik, Abteilung II fuer Onkologie, Haematologie, Immunologie, Rheumatologie und Pulmologie, Otfried Mueller Str. 10, 72076, Tuebingen, Germany.
authors.forename: Wichard
authors.initials: W
authors.lastname: Vogel
authors.affiliation: Medizinische Universitaetsklinik, Abteilung II fuer Onkologie, Haematologie, Immunologie, Rheumatologie und Pulmologie, Otfried Mueller Str. 10, 72076, Tuebingen, Germany.
authors.forename: Wolfgang A
authors.initials: WA
authors.lastname: Bethge
authors.affiliation: Interfakultaeres Institut fuer Zellbiologie, Abteilung Immunologie, Auf der Morgenstelle 15, 72076, Tuebingen, Germany.
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Rammensee
authors.affiliation: Medizinische Universitaetsklinik, Abteilung II fuer Onkologie, Haematologie, Immunologie, Rheumatologie und Pulmologie, Otfried Mueller Str. 10, 72076, Tuebingen, Germany.
authors.forename: Lothar
authors.initials: L
authors.lastname: Kanz
authors.affiliation: Medizinische Universitaetsklinik, Abteilung IV fuer Endokrinologie, Diabetologie, Angiologie, Nephrologie und Klinische Chemie, Otfried Mueller Str. 10, 72076, Tuebingen, Germany.|Institute of Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Center Munich at the University of Tuebingen, Tuebingen, Germany.|German Center for Diabetes Research (DZD), Muenchen-Neuherberg, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Heni
mesh_terms: D000328:Adult; D000368:Aged; D000740:Anemia / Q000097:blood* / Q000209:etiology / Q000276:immunology / Q000473:pathology; D014408:Biomarkers, Tumor / Q000097:blood*; D001772:Blood Cell Count; D001853:Bone Marrow / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D005260:Female; D006085:Graft Survival / Q000276:immunology / Q000502:physiology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000097:blood* / Q000188:drug therapy / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood* / Q000188:drug therapy / Q000628:therapy*; D014527:Uric Acid / Q000097:blood*; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D014527:Uric Acid
keywords: Allogeneic hematopoietic cell transplantation; Autologous stem cell transplantation; Danger signal; Leukemia; Uric acid