ABSTRACT
Mycophenolate mofetil (MMF), in combination with a calcineurin inhibitor, is used as the prophylaxis for graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation (HCT). Compared to intravenous methotrexate (MTX), MMF is associated with a lower incidence of mucositis and shorter time for hematopoietic engraftment but comparable incidence of acute GVHD, resulting in the preferred use of MMF for GVHD prophylaxis in elderly patients or those undergoing cord blood transplantation (CBT). Although several studies have evaluated the clinical impact of MTX omission due to toxicity after allogeneic HCT, the impact of oral MMF interruption for GVHD prophylaxis on transplant outcomes remains unclear. Therefore, in this study, we retrospectively analyzed the consecutive data of adult patients who underwent single-unit unrelated CBT and received oral MMF in combination with cyclosporine for GVHD prophylaxis at our hospital. Among the 53 patients, the planned dose of MMF was interrupted in 14 with a median of 19.5 d (range, 3-27 d) of CBT. In multivariate analysis, MMF interruption, which was treated as a time-dependent covariate, was significantly associated with poorer overall survival (hazard ratio [HR], 5.41; 95% confidence interval [CI], 2.03-14.43; P < 0.001) and higher non-relapse mortality (HR, 7.56; 95% CI, 1.99-28.79; P = 0.002). Further studies with larger cohorts are necessary to confirm the clinical significance of oral MMF interruption in GVHD prophylaxis.
ABSTRACT
Although varicella zoster virus (VZV) disease is a common complication after allogeneic hematopoietic cell transplantation (HCT), research into the long-term incidence of VZV disease in adults receiving cord blood transplantation (CBT) has been limited. The objective of this study was to evaluate the incidence, risk factors, and clinical impact of VZV disease after CBT with long-term follow-up in our institution. We retrospectively analyzed the data for 156 adult patients who received single-unit CBT at our institution between 2007 and 2020 and who achieved neutrophil engraftment and survived at least 100 days without recurrence of the underlying disease. VZV disease occurred in 61 patients at a median of 608 days (range, 36 to 4090 days) after CBT. The cumulative incidence of VZV disease was 14% (95% confidence interval [CI], 9% to 20%) at 1 year post-CBT and 40% (95% CI, 31% to 48%) at 5 years post-CBT. Multivariate analysis identified the cessation of antiviral prophylaxis as an independent risk factor for an elevated risk of VZV disease (hazard ratio, 15.65; 95% CI, 6.59 to 37.21; P < .001). The cumulative incidence of VZV disease was significantly lower in the long-term antiviral prophylaxis group (who received prophylaxis for approximately 1 year after CBT or to the end of immunosuppressive therapy) compared with the short-term antiviral prophylaxis group (who received prophylaxis for 35 days after CBT) (P = .005). Among the patients who developed VZV disease, the median time to onset of VZV disease was significantly delayed in the long-term antiviral prophylaxis group compared with the short-term antiviral prophylaxis group (694 days versus 130 days; P < .001), but the median onset of VZV disease after the cessation of antiviral prophylaxis was not significantly different between the 2 groups (166 days versus 95 days; P = .087). These data demonstrate that the long-term incidence of VZV disease is relatively high in adult patients undergoing CBT. Given that the incidence of VZV disease remained high after the cessation of antiviral prophylaxis, additional interventions, such as recombinant zoster vaccine administration, could be required to prevent VZV disease in long-term adult survivors after CBT.
