Everolimus and mycophenolate mofetil effectively prevent GvHD in children with severe acute kidney injury undergoing allogeneic HSCT

Allogeneic hematopoietic stem cell transplantation (HSCT) serves as a therapeutic intervention for various pediatric diseases. Acute kidney injury afflicts 21-84% of pediatric HSCT cases, significantly compromising clinical outcomes. This retrospective single-institution analysis scrutinized the practice of substituting nephrotoxic ciclosporin A with the everolimus/mycophenolate mofetil combination as graft-versus-host disease (GVHD) prophylaxis in 57 patients following first allogeneic matched donor HSCT. The control cohort comprised 74 patients not receiving everolimus during the same timeframe. Study endpoints encompassed the emergence of retention parameters subsequent to the switch to everolimus, overall survival, relapse incidence of the underlying disease and acute and chronic GVHD in both treatment groups. Our findings reveal a significant improvement in renal function, evidenced by reduced creatinine and cystatin C levels 14 days after ceasing ciclosporin A and initiating everolimus treatment. Crucially, the transition to everolimus did not adversely affect overall survival post-HSCT (HR 1.4; 95% CI: 0.64 – 3.1; p=0.39). Comparable incidences of grade 2-4 and grade 3-4 acute GVHD as well as severe chronic GVHD were observed in both groups. Patients with an underlying malignant disease exhibited similar event-free survival in both treatment arms (HR 0.87, 95% CI: 0.39 – 1.9, p=0.73). This study provides compelling real-world clinical evidence supporting the feasibility of replacing CsA with everolimus and for the use of the everolimus/mycophenolate mofetil combination to manage acute kidney injury following HSCT in children. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study did not receive any funding. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study was ethically approved by the institutional review board, Charite's Ethics Committee, under the reference EA2/144/15. This study adheres to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) principles. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors.