title: Higher Dose of Mycophenolate Mofetil Reduces Acute Graft-versus-Host Disease in Reduced-Intensity Conditioning Double Umbilical Cord Blood Transplantation.
abstract: Mycophenolate mofetil (MMF) is frequently used in hematopoietic cell transplantation (HCT) for graft-versus-host disease (GVHD) prophylaxis and to facilitate engraftment. We previously reported that a higher level of mycophenolic acid can be achieved with an MMF dose of 3 g/day than with 2 g/day. Here, we retrospectively compared clinical outcomes of reduced-intensity conditioning (RIC) double umbilical cord blood (dUCB) HCT recipients receiving cyclosporine A with MMF 2 g (n = 93) versus 3 g (n = 175) daily. Multiple regression analysis adjusted for antithymocyte globulin in the conditioning revealed that MMF 3 g/day led to a 49% relative risk (RR) reduction in grade II to IV acute GVHD rate (RR, .51; 95% confidence interval, .36 to .72; P < .01). However, the higher MMF dose was not protective for chronic GVHD. Additionally, MMF dose was not an independent predictor of neutrophil engraftment or treatment-related mortality at 6 months or 2-year post-transplantation disease relapse, disease-free survival, or overall survival. Higher MMF dose did not increase risk of infectious complications, and infection-related mortality was similar for both MMF doses. Our data indicate that MMF 3 g/day reduces the risk of acute GVHD without affecting other clinical outcomes and should be used for GVHD prophylaxis after RIC dUCB transplantation.
authors: Division of Hematology, Oncology and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, Minnesota. Electronic address: nbejanya@umn.edu.
authors: Nelli
authors: N
authors: Bejanyan
authors: Departments of Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis, Minnesota.
authors: John
authors: J
authors: Rogosheske
authors: Biostatistics and Bioinformatics Core, Masonic Cancer Center, Minneapolis, Minnesota.
authors: Todd
authors: T
authors: DeFor
authors: Division of Hematology, Oncology and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, Minnesota.
authors: Aleksandr
authors: A
authors: Lazaryan
authors: Departments of Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis, Minnesota.
authors: Kelli
authors: K
authors: Esbaum
authors: Division of Hematology, Oncology and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, Minnesota.
authors: Shernan
authors: S
authors: Holtan
authors: Division of Hematology, Oncology and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, Minnesota.
authors: Mukta
authors: M
authors: Arora
authors: Division of Blood and Marrow Transplantation, Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota.
authors: Margaret L
authors: ML
authors: MacMillan
authors: Division of Hematology, Oncology and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, Minnesota.
authors: Daniel
authors: D
authors: Weisdorf
authors: Departments of Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis, Minnesota.
authors: Pamala
authors: P
authors: Jacobson
authors: Division of Blood and Marrow Transplantation, Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota.
authors: John
authors: J
authors: Wagner
authors: Division of Hematology, Oncology and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, Minnesota.
authors: Claudio G
authors: CG
authors: Brunstein
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000961:Antilymphocyte Serum / Q000008:administration & dosage*; D036101:Cord Blood Stem Cell Transplantation; D018572:Disease-Free Survival; D006086:Graft vs Host Disease / Q000401:mortality / Q000517:prevention & control; D019337:Hematologic Neoplasms / Q000401:mortality / Q000628:therapy; D006801:Humans; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives*; D015996:Survival Rate; D019172:Transplantation Conditioning
chemical_list: D000961:Antilymphocyte Serum; D009173:Mycophenolic Acid
keywords: Graft-versus-host disease; Mycophenolate mofetil; Reduced-intensity conditioning; Transplantation; Umbilical cord blood
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