Addition of mycophenolate mofetil to a calcineurin inhibitor and post-transplant cyclophosphamide results in lower incidence of extensive chronic graft-versus-host disease in HLA-matched allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia in complete remission: a matched-pair analysis on behalf of the Acute Leukemia Working Party of the EBMT.

Whether one or two agents added to post-transplant cyclophosphamide (PTCy) are needed in HLA-matched allogeneic hematopoietic stem cell transplantation (allo-HSCT) with peripheral blood stem cells (PBSC) is debated. We retrospectively compared PTCy in association with a calcineurin inhibitor (PTCy+CNI) or with a CNI plus mycophenolate mofetil (PTCy+CNI+MMF) in adult patients transplanted for acute myeloid leukemia in first complete remission and receiving PBSC in the period from 2010 to 2020. Propensity score matching was performed using exact matching for donor type (related or unrelated) and the nearest neighbor for other variables (i.e. age, adverse cytogenetics, Karnofsky performance status, patient and donor cytomegalovirus serology, conditioning intensity). Each group comprised 146 patients, with 63% in total undergoing matched unrelated-allo-HSCT. Median follow up was longer for PTCy+CNI (36 [IQR 31-39] months versus 25 [IQR 19-30] months for PTCy+CNI+MMF, p < 0.01). At 2 years, PTCy+CNI was associated with a higher incidence of extensive chronic GVHD (16% [95% CI 10-22] versus 6% [95% CI 3-12] for PTCy+CNI+MMF, p < 0.03) while no differences were observed for all the other transplant outcomes. Addition of MMF to PTCy and CNI may help to prevent extensive chronic GVHD in HLA-matched allo-HSCT with PBSC.