Comparative Study of Mizoribine and Mycophenolate Mofetil Combined with a Calcineurin Inhibitor-Based Immunosuppressive Regimen in Patients with Alternative Donor Hematopoietic Cell Transplantation

Biol Blood Marrow Transplant. 2020 Sep;26(9):1663-1669. doi: 10.1016/j.bbmt.2020.05.022. Epub 2020 Jun 3.


Cytomegalovirus (CMV) infection and graft-versus-host disease (GVHD) remain the major causes of nonrelapse mortality (NRM) in patients following alternative donor hematopoietic stem cell transplantation (HCT). Mizoribine (MZR) showed an anti-CMV effect in addition to its immunosuppressive effect in patients with renal transplantation. In this study, we aimed to evaluate the efficacy and safety of MZR combined with a calcineurin inhibitor (CNI) as a method of prophylactic immunosuppression in recipients following alternative donor HCT. Eighty patients were enrolled in the study and randomized to the MZR (n = 40) or MMF (n = 40) cohort before transplantation conditioning. Analyses involved a comparison of the outcomes between the 2 cohorts, as well as risk analyses of early nonrelapse mortality (NRM) and severe CMV infection. In contrast to MMF, MZR was associated with a lower but statistically nonsignificant median CMV DNA peak load (P = .075), significantly fewer episodes of persistent/refractory infection (odds ratio [OR], .12), and a lower failure rate of CMV treatment (OR, .82), but a significantly higher rate of hyperuricemia (OR, 2.75). Transplantation efficacy was comparable in the 2 cohorts regarding engraftment, the development of secondary poor graft function and GVHD, and the estimated OS and PFS. The 1-year NRM of the MZR cohort did not differ from that of the MMF cohort, whereas the rate of 1-year NRM caused by viral infections was reduced in the MZR cohort and was of borderline statistical significance (P = .05). In the multivariate analysis, lower doses of CD34+ cells in grafts (hazard ratio [HR], 3.65) and persistent/refractory CMV infections (versus no CMV infection: HR, 7.31; versus CMV infection that was not persistent/refractory: HR, 4.46) were predictors of increased 1-year NRM. The use of MMF (versus MZR cohort: OR, 11.54) and grade II-IV acute GVHD (OR, 15.32) were independent risk factors for developing persistent/refractory CMV infection. When combined with CNIs, MZR functioned well in terms of both immunosuppression and reduced severity of CMV infection; however, further studies are warranted to verify its use as a potential immunosuppressant for alternative donor HCT.

Keywords: CMV infection; Hematopoietic cell transplantation; Mizoribine; Mycophenolate mofetil.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Calcineurin Inhibitors / therapeutic use
  • Graft vs Host Disease* / prevention & control
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Mycophenolic Acid / therapeutic use
  • Ribonucleosides
  • Transplantation Conditioning


  • Calcineurin Inhibitors
  • Immunosuppressive Agents
  • Ribonucleosides
  • mizoribine
  • Mycophenolic Acid