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.
Keywords: GVHD; MMF; bone marrow transplantation; relapse; umbilical cord blood.
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