TY - JOUR
T1 - Weight-based mycophenolate mofetil dosing predicts acute GVHD and relapse after allogeneic hematopoietic cell transplantation
AU - Bejanyan, Nelli
AU - Rogosheske, John
AU - Cao, Qing
AU - Lazaryan, Aleksandr
AU - Holtan, Shernan
AU - Ustun, Celalettin
AU - Jacobson, Pamala
AU - MacMillan, Margaret
AU - Weisdorf, Daniel J.
AU - Wagner, John
AU - Arora, Mukta
AU - Brunstein, Claudio G.
N1 - 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)
PY - 2021/2
Y1 - 2021/2
N2 - 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.
AB - 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.
KW - GVHD
KW - MMF
KW - bone marrow transplantation
KW - relapse
KW - umbilical cord blood
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U2 - 10.1111/ejh.13537
DO - 10.1111/ejh.13537
M3 - Article
C2 - 33084139
AN - SCOPUS:85097287903
VL - 106
SP - 205
EP - 212
JO - European Journal of Haematology
JF - European Journal of Haematology
SN - 0902-4441
IS - 2
ER -