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Recipient pretransplant inosine monophosphate dehydrogenase activity in nonmyeloablative hematopoietic cell transplantation.
- Source :
-
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation [Biol Blood Marrow Transplant] 2014 Oct; Vol. 20 (10), pp. 1544-52. Date of Electronic Publication: 2014 Jun 09. - Publication Year :
- 2014
-
Abstract
- Mycophenolic acid, the active metabolite of mycophenolate mofetil (MMF), inhibits inosine monophosphate dehydrogenase (IMPDH) activity. IMPDH is the rate-limiting enzyme involved in de novo synthesis of guanosine nucleotides and catalyzes the oxidation of inosine 5'-monophosphate to xanthosine 5'-monophosphate (XMP). We developed a highly sensitive liquid chromatography-mass spectrometry method to quantitate XMP concentrations in peripheral blood mononuclear cells (PMNCs) isolated from the recipient pretransplant and used this method to determine IMPDH activity in 86 nonmyeloablative allogeneic hematopoietic cell transplantation (HCT) patients. The incubation procedure and analytical method yielded acceptable within-sample and within-individual variability. Considerable between-individual variability was observed (12.2-fold). Low recipient pretransplant IMPDH activity was associated with increased day +28 donor T cell chimerism, more acute graft-versus-host disease (GVHD), lower neutrophil nadirs, and more cytomegalovirus reactivation but not with chronic GVHD, relapse, nonrelapse mortality, or overall mortality. We conclude that quantitation of the recipient's pretransplant IMPDH activity in PMNC lysate could provide a useful biomarker to evaluate a recipient's sensitivity to MMF. Further trials should be conducted to confirm our findings and to optimize postgrafting immunosuppression in nonmyeloablative HCT recipients.<br /> (Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Acute Disease
Adult
Aged
Biomarkers metabolism
Female
Graft Survival
Hematologic Neoplasms diagnosis
Hematologic Neoplasms immunology
Hematologic Neoplasms mortality
Humans
IMP Dehydrogenase antagonists & inhibitors
Inosine Monophosphate metabolism
Leukocytes, Mononuclear immunology
Leukocytes, Mononuclear pathology
Male
Middle Aged
Mycophenolic Acid therapeutic use
Prognosis
Prospective Studies
Recurrence
Ribonucleotides antagonists & inhibitors
Ribonucleotides biosynthesis
Survival Analysis
Transplantation Chimera genetics
Transplantation Chimera immunology
Transplantation, Homologous
Xanthine
Graft vs Host Disease prevention & control
Hematologic Neoplasms therapy
Hematopoietic Stem Cell Transplantation
IMP Dehydrogenase metabolism
Immunosuppressive Agents therapeutic use
Leukocytes, Mononuclear enzymology
Mycophenolic Acid analogs & derivatives
Subjects
Details
- Language :
- English
- ISSN :
- 1523-6536
- Volume :
- 20
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation
- Publication Type :
- Academic Journal
- Accession number :
- 24923537
- Full Text :
- https://doi.org/10.1016/j.bbmt.2014.05.032