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

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Item Type:	Preprint
Title:	Everolimus and mycophenolate mofetil effectively prevent GvHD in children with severe acute kidney injury undergoing allogeneic HSCT
Creators Name:	Zirngibl, F., Gebert, P., Materne, B., Launspach, M., Künkele, A., Hundsdoerfer, P., Cyrull, S., Deubzer, H.E., Kühl, J.S., Eggert, A., Lang, P., Oevermann, L., von Stackelberg, A. and Schulte, J.H.
Abstract:	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.
Source:	medRxiv
Publisher:	Cold Spring Harbor Laboratory Press
Article Number:	2024.03.14.24304155
Date:	16 March 2024
Official Publication:	https://doi.org/10.1101/2024.03.14.24304155

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