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 - Publisher Copyright:
© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
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
SN - 0902-4441
VL - 106
SP - 205
EP - 212
JO - European Journal of Haematology
JF - European Journal of Haematology
IS - 2
ER -