Weight-based mycophenolate mofetil dosing predicts acute GVHD and relapse after allogeneic hematopoietic cell transplantation

Nelli Bejanyan, John Rogosheske, Qing Cao, Aleksandr Lazaryan, Shernan Holtan, Celalettin Ustun, Pamala Jacobson, Margaret MacMillan, Daniel J. Weisdorf, John Wagner, Mukta Arora, Claudio G. Brunstein

Research output: Contribution to journalArticlepeer-review

Abstract

Objectives: Higher MMF dose can reduce acute GVHD risk after allogeneic hematopoietic cell transplantation (HCT). We examined the effect of MMF dose, relative to patient actual body weight (mg/kg/day), on outcomes of 680 adults after HCT. Methods: MMF was combined with cyclosporine (n = 599) or sirolimus (n = 81). We divided MMF dose/kg/day in quartiles. Results: The median time to grade II-IV acute GVHD was 32 days. The incidence of grade II-IV acute GVHD at day 30 was 30% in 1st (<29), 20% in 2nd (29-34), 16% in 3rd (35-41), and 19% in 4th (≥42) quartile (P <.01). Corresponding relapse incidence at 1 year was 16%, 25%, 27%, and 31%, respectively (P =.01). In multivariate analysis, as compared to 1st quartile, higher dose of weight-based MMF reduced grade II-IV acute GVHD (HR = 0.64 for 2nd, HR = 0.48 for 3rd, and HR = 0.55 for 4th quartile), but increased the risk of relapse (HR = 1.63 for 2nd, HR = 1.75 for 3rd, and HR = 2.31 for 4th quartile). Conclusions: Weight-based MMF dose had no significant impact on engraftment, chronic GVHD, or survival. These data suggest that higher weight-based MMF dose reduces the risk of acute GVHD at the expense of increased relapse and supports conducting prospective studies to optimize MMF dosing after HCT.

Original languageEnglish (US)
Pages (from-to)205-212
Number of pages8
JournalEuropean Journal of Haematology
Volume106
Issue number2
DOIs
StatePublished - Feb 2021

Bibliographical note

Funding Information:
This work was funded in part by National Institutes of Health, National Cancer Institute grant P01 CA65493 (CGB and JEW), and P30 CA77598 utilizing the Biostatistics and Bioinformatics Core shared resource of the Masonic Cancer Center, University of Minnesota (QC)

Publisher Copyright:
© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

Keywords

  • GVHD
  • MMF
  • bone marrow transplantation
  • relapse
  • umbilical cord blood

PubMed: MeSH publication types

  • Journal Article

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