A Japanese Multicenter Study of High-Dose Mizoribine Combined With Cyclosporine, Basiliximab, and Corticosteroid in Renal Transplantation (The Fourth Report)

Oshiro, Yoshinori; Nakagawa, Kanako; Hoshinaga, Kiyotaka; Aikawa, Atushi; Shishido, Seiichirou; Yoshida, Kôji; Asano, Takeru; Murai, Minoru; Hasegawa, Akira

doi:10.1016/j.transproceed.2013.03.016

Cited by 8 publications

(6 citation statements)

References 8 publications

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“…Nevertheless, the present study suggests that MZR showed good immunosuppressive as well as antiviral effects in the setting of HCT, which is similar to the results in a series of reports on renal transplantation [11,[16][17][18][19]. GVHD is the most important immune event that must be overcome in HCT, similar to graft rejection in solid organ transplantation.…”

Section: Discussionsupporting

confidence: 90%

“…First, we did not monitor the serum concentrations of MZR or MMF and thus could not further accurately determine their effects. Second, we did not include a high-dose group in the trial, because previous studies have illustrated that, unlike a daily dose of 1 to 3 mg/kg, high-dose MZR or MZR at a high trough level is correlated with decreased risks of acute rejection and CMV infection in renal transplantation [16][17][18][19]. Furthermore, the scheme used in this study did not record episodes of diarrhea in the adverse event files because of concerns about not accurately determining the true causes of diarrhea in the HCT setting; another study found that treatment with MZR was associated with fewer episodes of diarrhea compared with treatment with MMF in renal transplantation [11].…”

Section: Discussionmentioning

confidence: 99%

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

Huang

Han

Yang

et al. 2020

Biology of Blood and Marrow Transplantation

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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.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

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

Huang

Han

Yang

et al. 2020

Biology of Blood and Marrow Transplantation

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“…In 2013, Oshiro et al concluded that four-drug combination therapy using high-dose MZR (8 mg/ kg/day), CyA, basiliximab and corticosteroids in renal transplant recipients was effective and safe. 10 They also reported MZR trough levels >2.5 mg/mL were effective to prevent acute rejection episodes.…”

Section: Discussionmentioning

confidence: 99%

High‐dose mizoribine combined with calcineurin inhibitor (cyclosporine or tacrolimus), basiliximab and corticosteroids for renal transplantation: A Japanese multicenter study

et al. 2017

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“…Mizoribine (MZR), an imidazole nucleoside analog isolated from the mold Eupenicillium brefeldianum, is an immunosuppressive agent that has been used extensively in the management of post-transplant immunosuppression and autoimmune diseases [5]. Similar to mycophenolate mofetil (MMF), MZR inhibits cellular and humoral immune responses by blocking inosine 5-monophosphate dehydrogenase, which is a rate-limiting enzyme for de novo purine synthesis and critical for the proliferation of T and B lymphocytes [6].…”

mentioning

confidence: 99%

Conversion from mycophenolate mofetil to mizoribine in the early stages of BK polyomavirus infection could improve kidney allograft prognosis: a single-center study from China

Cheng

Wen

et al. 2021

BMC Nephrol

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Background Some studies have suggested mizoribine (MZR) could inhibit the replication of BK polyomavirus (BKPyV). The purpose of this study was to explore whether conversion from mycophenolate mofetil (MMF) to MZR in the early stages of BKPyV infection can improve kidney allograft prognosis. Methods Twenty-one kidney transplant recipients with BKPyV viruria/viremia and ten with BK polyomavirus-associated allograft nephropathy (BKPyVAN) received MZR conversion therapy were retrospectively identified. The clearance rate of urine and blood BKPyV DNA, change of serum creatinine (SCr), uric acid (UA), hemoglobin (HB), white blood cell (WBC), lymphocyte ratio, platelet (PLT), routine urinalysis, panel reactive antibody (PRA), and gastrointestinal disorders during follow-up of the 2 groups were evaluated and compared. Results After MZR conversion therapy, the clearance rate of urine and blood viral load in BKPyV viruria/viremia group were 85.7 and 100 %, while that in BKPyVAN were 40 and 87.5 %, respectively. Stable SCr were observed in all cases of BKPyV viruria/viremia group, while that of BKPyVAN was only 40 % (P < 0.001) and one even progressed to end-stage renal disease. The results of routine urinalysis in the two groups showed no significant changes before and after MZR conversion therapy. However, in BKPyV viruria/viremia group, four cases developed acute rejection and one had positive PRA-II but no donor specific antibody, requiring conversion back to MMF. Hyperuricemia was the common adverse effect of MZR. Conclusions Conversion from MMF to MZR could help clear BKPyV infection. As compared to BKPyVAN, patients who underwent initiation of MZR conversion therapy in the early stages of BKPyV infection maintained stable allograft function. Prospective studies with larger sample size are needed to ascertain this preliminary finding.

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A Japanese Multicenter Study of High-Dose Mizoribine Combined With Cyclosporine, Basiliximab, and Corticosteroid in Renal Transplantation (The Fourth Report)

Cited by 8 publications

References 8 publications

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

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

High‐dose mizoribine combined with calcineurin inhibitor (cyclosporine or tacrolimus), basiliximab and corticosteroids for renal transplantation: A Japanese multicenter study

Conversion from mycophenolate mofetil to mizoribine in the early stages of BK polyomavirus infection could improve kidney allograft prognosis: a single-center study from China

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