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Lower Weight-Based Mycophenolate Mofetil Dosing is Associated with Superior Outcomes after Haploidentical
Hany Elmariah1, Salman Otoukesh2, Ambuj Kumar3
1Department of Blood and Marrow Transplant and Cellular Immunotherapy, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
Abstract:
Mycophenolate mofetil (MMF) is commonly included in post-transplant cyclophosphamide (PTCy) based graft-versus-host disease (GVHD) prophylaxis after haploidentical (haplo) hematopoietic cell transplant (HCT). In the non-PTCy setting, higher MMF dose/kg has been shown to reduce rates of acute graft-versus-host disease (GVHD). When used in conjunction with PTCy, MMF is dosed at 15 mg/kg three times daily up to a maximum dose of 3 g/day. Thus, patients who weigh ≥67 kg receive 3 g/day and a variable dose/kg of MMF. We investigated the impact of MMF dose/kg on clinical outcomes following haploidentical PBSCT with PTCy-based GVHD prophylaxis. All consecutive adult patients with hematologic malignancies receiving haploidentical T cell replete peripheral blood stem cell transplant (PBSCT) with PTCy/MMF and either tacrolimus or sirolimus at the Moffitt Cancer Center or City of Hope between April 2014-August 2020 were included. For analyses, MMF dose relative to patient actual body weight (mg/kg/day), was stratified into categories of low (<29 mg/kg/day), low intermediate (29-34 mg/kg/day), high intermediate (35-41 mg/kg/day), and high (>41 mg/kg/day). Three hundred eighty-six patients were included. Of these, 54 patients received low dose, 73 low intermediate, 137 high intermediate and 122 high dose MMF by relative weight exposure. In multivariate analysis, low MMF dose exposure was associated with reduced rates of relapse in comparison to the high dose group (HR = 0.45, 95% CI: 0.21 to 0.94, P = .03). This led to superior PFS among patients with low compared to high MMF dose exposure (HR = 0.58, 95% CI: 0.34 to 0.99, P = .045). MMF relative dose exposure was not associated with engraftment, GVHD, nonrelapse mortality, or OS. In this study of patients receiving haploidentical PBSCT with PTCy based GVHD prophylaxis, low MMF dose/kg was associated with improved rates of relapse and PFS. Future prospective studies should investigate optimal dosing strategies of MMF when given with the PTCy regimen.
Insights
Lower doses of mycophenolate mofetil (MMF) correlate with reduced relapse and improved progression-free survival (PFS) after haploidentical stem cell transplants using post-transplant cyclophosphamide (PTCy) prophylaxis. Further research is needed for optimal MMF dosing strategies.
Area of Science:
- Hematology
- Immunology
- Oncology
Background:
- Mycophenolate mofetil (MMF) is a standard component of graft-versus-host disease (GVHD) prophylaxis following haploidentical (haplo) hematopoietic cell transplant (HCT) with post-transplant cyclophosphamide (PTCy).
- In non-PTCy regimens, higher MMF doses are linked to reduced acute GVHD rates.
- MMF dosing in PTCy-based regimens is weight-based, leading to variable mg/kg doses for patients weighing over 67 kg.
Purpose of the Study:
- To assess the impact of MMF dose per kilogram (mg/kg/day) on clinical outcomes in patients undergoing haploidentical peripheral blood stem cell transplantation (PBSCT) with PTCy-based GVHD prophylaxis.
- To investigate the relationship between MMF dose stratification and rates of relapse, GVHD, survival, and engraftment.
Main Methods:
- Retrospective analysis of 386 adult patients with hematologic malignancies who received haploidentical T cell replete PBSCT with PTCy/MMF and either tacrolimus or sirolimus.
- Patients were stratified into four MMF dose categories based on actual body weight: low (<29 mg/kg/day), low intermediate (29-34 mg/kg/day), high intermediate (35-41 mg/kg/day), and high (>41 mg/kg/day).
- Multivariate analysis was used to evaluate the association between MMF dose and clinical outcomes, including relapse, progression-free survival (PFS), GVHD, nonrelapse mortality (NRM), and overall survival (OS).
Main Results:
- Lower MMF dose exposure (<29 mg/kg/day) was significantly associated with reduced relapse rates compared to the high dose group (HR=0.45, P=.03).
- Patients receiving lower MMF doses demonstrated superior PFS compared to those receiving high doses (HR=0.58, P=.045).
- MMF dose relative to body weight was not found to be associated with engraftment, GVHD incidence, NRM, or OS.
Conclusions:
- In haploidentical PBSCT with PTCy-based GVHD prophylaxis, lower MMF doses per kilogram are associated with improved relapse rates and PFS.
- Current weight-based dosing may result in suboptimal MMF exposure for some patients.
- Prospective studies are warranted to determine optimal MMF dosing strategies within PTCy-based regimens.
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