title: Intensified Mycophenolate Mofetil Dosing and Higher Mycophenolic Acid Trough Levels Reduce Severe Acute Graft-versus-Host Disease after Double-Unit Cord Blood Transplantation.
abstract: Although mycophenolate mofetil (MMF) has replaced corticosteroids as immunosuppression in cord blood transplantation (CBT), optimal MMF dosing has yet to be established. We intensified MMF dosing from every 12 to every 8 hours to augment graft-versus-host disease (GVHD) prophylaxis in double-unit cord blood transplantation (dCBT) and evaluated outcomes according to the total daily MMF dose/kg in 174 dCBT recipients (median age, 39 years; range, 1 to 71) who underwent transplantation for hematologic malignancies. Recipients of an MMF dose ≤ the median (36 mg/kg/day) had an increased day 100 grade III and IV acute GVHD (aGVHD) incidence compared with patients who received >36 mg/kg/day (24% versus 8%, P = .008). Recipients of ≤ the median dose who had highly HLA allele (1 to 3 of 6) mismatched dominant units had the highest day 100 grade III and IV aGVHD incidence of 37% (P = .009). This finding was confirmed in multivariate analysis (P = .053). In 83 patients evaluated for mycophenolic acid (MPA) troughs, those with a mean week 1 and 2 trough < .5 μg/mL had an increased day 100 grade III and IV aGVHD of 26% versus 9% (P = .063), and those who received a low total daily MMF dose and had a low mean week 1 and 2 MPA trough had a 40% incidence (P = .008). Higher MMF dosing or MPA troughs had no impact on engraftment after myeloablation. This analysis supports intensified MMF dosing in milligram per kilogram per day and MPA trough level monitoring early after transplantation in dCBT recipients.
authors: Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York; Department of Pharmacy, Memorial Sloan Kettering Cancer Center, New York, New York. Electronic address: harnicas@mskcc.org.
authors: Stephen
authors: S
authors: Harnicar
authors: Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York; Department of Medicine, Weill Cornell Medical College, New York, New York.
authors: Doris M
authors: DM
authors: Ponce
authors: Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York.
authors: Patrick
authors: P
authors: Hilden
authors: Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York.
authors: Junting
authors: J
authors: Zheng
authors: Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York.
authors: Sean M
authors: SM
authors: Devlin
authors: Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
authors: Marissa
authors: M
authors: Lubin
authors: Department of Pharmacy, Memorial Sloan Kettering Cancer Center, New York, New York; Bone Marrow Transplantation Service, Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York.
authors: Melissa
authors: M
authors: Pozotrigo
authors: Department of Pharmacy, Memorial Sloan Kettering Cancer Center, New York, New York.
authors: Sherry
authors: S
authors: Mathew
authors: Department of Pharmacy, Memorial Sloan Kettering Cancer Center, New York, New York.
authors: Nelly
authors: N
authors: Adel
authors: Bone Marrow Transplantation Service, Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York.
authors: Nancy A
authors: NA
authors: Kernan
authors: Bone Marrow Transplantation Service, Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York.
authors: Richard
authors: R
authors: O'Reilly
authors: Bone Marrow Transplantation Service, Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York.
authors: Susan
authors: S
authors: Prockop
authors: Bone Marrow Transplantation Service, Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York.
authors: Andromachi
authors: A
authors: Scaradavou
authors: Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York; Department of Medicine, Weill Cornell Medical College, New York, New York.
authors: Alan
authors: A
authors: Hanash
authors: Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York; Department of Medicine, Weill Cornell Medical College, New York, New York.
authors: Robert
authors: R
authors: Jenq
authors: Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York; Department of Medicine, Weill Cornell Medical College, New York, New York.
authors: Marcel
authors: M
authors: van den Brink
authors: Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York; Department of Medicine, Weill Cornell Medical College, New York, New York.
authors: Sergio
authors: S
authors: Giralt
authors: Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York; Department of Medicine, Weill Cornell Medical College, New York, New York.
authors: Miguel A
authors: MA
authors: Perales
authors: Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York; Department of Medicine, Weill Cornell Medical College, New York, New York.
authors: James W
authors: JW
authors: Young
authors: Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York; Department of Medicine, Weill Cornell Medical College, New York, New York.
authors: Juliet N
authors: JN
authors: Barker
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D036101:Cord Blood Stem Cell Transplantation; D005260:Female; D006086:Graft vs Host Disease / Q000097:blood / Q000517:prevention & control; D019337:Hematologic Neoplasms / Q000097:blood / Q000628:therapy; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*
chemical_list: D009173:Mycophenolic Acid
keywords: Cord blood transplantation; Graft-versus-host disease; Mycophenolate mofetil; Pharmacokinetics