Everolimus with or without Mycophenolate Mofetil for Graft-versus-Host Disease Prophylaxis after Hematopoietic Stem Cell Transplantation in Children with Acute Kidney Injury: A Single-Center Retrospective Analysis.

Hematopoietic stem cell transplantation (HSCT) serves as a therapeutic intervention for various pediatric diseases. Acute and chronic graft-versus-host disease (GVHD) are decisive determinants of successful allogeneic HSCT. The immunosuppressive agent cyclosporin A (CsA) is most often used to prevent GVHD in pediatric patients, but it is known to be nephrotoxic. Acute kidney injury (AKI) affects 17% to 47% of pediatric HSCT recipients, compromising clinical outcomes. This retrospective single-institution analysis scrutinized the practice of substituting nephrotoxic CsA with an everolimus/mycophenolate mofetil (MMF) combination as GVHD prophylaxis in 57 patients with AKI (n = 53) or central nervous system side effects due to calcineurin inhibitor (CNI) treatment (n = 4) following first allogeneic HSCT. This retrospective cohort study analyzed the clinical courses of 57 children who were switched from CNI-based GVHD prophylaxis (CsA or tacrolimus in single cases) to the everolimus/MMF combination (n = 48) or everolimus alone (n = 9) after undergoing their first allogeneic HSCT at the Charité University Medicine Berlin. Serving as a control group were 74 patients undergoing their first allogeneic HSCT during the same period who did not receive everolimus at any time post-transplantation. Patients undergoing mismatched family donor transplantation without subsequent CNI treatment for GVHD prophylaxis were excluded. Study endpoints encompassed the retention parameter course subsequent to the GVHD prophylaxis switch, overall survival (OS), and incidences of underlying disease relapse and acute and chronic GVHD in both treatment groups. Renal function improved significantly after switching from CsA to the everolimus/MMF combination. Crucially, the transition to everolimus did not adversely affect OS following HSCT (hazard ratio [HR], 1.6; 95% confidence interval [CI], 0.74 to 3.5; P = .23), especially for patients with nonmalignant diseases (HR, 1.4; 95% CI, 0.34 to 5.9; P = .64). The incidences of grade III-IV acute GVHD (HR, 1.82; 95% CI, 0.45 to 7.4; P = .40) and severe chronic GVHD (HR, 2.76; 95% CI, 0.69 to 11.0; P = .15) were comparable in patients treated with the everolimus/MMF combination and those receiving standard CsA treatment in the control group. OS in patients with malignant underlying diseases was lower in the everolimus group (HR, 2.7; 95% CI, 1.1 to 6.9; P = .03), however, event-free survival was similar in patients with an underlying malignant disease treated with either the everolimus/MMF combination or CsA (HR, 0.87; 95% CI, 0.39 to 1.9; P = .73). Renal function improved significantly in patients who switched their immunosuppression regimen from CsA to everolimus with or without MMF cotreatment after diagnosis of AKI. Patient outcomes in the everolimus group were comparable to those in the control group. This study provides compelling real-world clinical evidence to support replacing CsA with the everolimus/MMF combination in the management of AKI following HSCT in children.