Intensified mycophenolate mofetil dosing and higher mycophenolic acid trough levels reduce severe acute graft-versus-host disease after double-unit cord blood transplantation Journal Article


Authors: Harnicar, S.; Ponce, D. M.; Hilden, P.; Zheng, J.; Devlin, S. M.; Lubin, M.; Pozotrigo, M.; Mathew, S.; Adel, N.; Kernan, N. A.; O'reilly, R.; Prockop, S.; Scaradavou, A.; Hanash, A.; Jenq, R.; Van Den Brink, M.; Giralt, S.; Perales, M. A.; Young, J. W.; Barker, J. N.
Article 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. © 2015 American Society for Blood and Marrow Transplantation.
Keywords: pharmacokinetics; graft-versus-host disease; cord blood transplantation; mycophenolate mofetil
Journal Title: Biology of Blood and Marrow Transplantation
Volume: 21
Issue: 5
ISSN: 1083-8791
Publisher: Elsevier Inc.  
Date Published: 2015-05-01
Start Page: 920
End Page: 925
Language: English
DOI: 10.1016/j.bbmt.2015.01.024
PROVIDER: scopus
PMCID: PMC4408232
PUBMED: 25687796
DOI/URL:
Notes: Export Date: 4 May 2015 -- Source: Scopus
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MSK Authors
  1. Junting Zheng
    172 Zheng
  2. Nancy Kernan
    477 Kernan
  3. Susan E Prockop
    226 Prockop
  4. Sergio Andres Giralt
    756 Giralt
  5. Alan M Hanash
    100 Hanash
  6. Doris Ponce
    186 Ponce
  7. Miguel-Angel Perales
    588 Perales
  8. Juliet N Barker
    296 Barker
  9. Robert R Jenq
    107 Jenq
  10. James W Young
    298 Young
  11. Richard O'Reilly
    679 O'Reilly
  12. Marissa N Lubin
    79 Lubin
  13. Nelly G Adel
    44 Adel
  14. Sherry Mathew
    14 Mathew
  15. Sean McCarthy Devlin
    444 Devlin
  16. Patrick Dale Hilden
    107 Hilden