Child protected by medical innovation after stem cell transplant

Beyond Calcineurin Inhibitors: New Strategies for Protecting Children After Stem Cell Transplants

Elliot Brynn in Health & Wellness December 2025 • 4 min read.

"Discover innovative, CNI-free methods that can help improve outcomes and reduce GVHD risk in children undergoing stem cell transplants."

Stem cell transplants offer hope for children battling serious diseases, but they're not without risks. Neurological complications, including posterior reversible encephalopathy syndrome (PRES), are a concern. PRES is a condition characterized by specific clinical and radiologic findings, often resolving with appropriate treatment. However, the drugs used to prevent graft-versus-host disease (GVHD), especially calcineurin inhibitors (CNIs), can sometimes contribute to these complications.

Researchers have been exploring alternative strategies that avoid CNIs to minimize the risk of PRES and other neurological issues. The goal is to find ways to manage GVHD effectively without relying on these potentially harmful drugs. This article dives into a study that examines the outcomes of children who underwent stem cell transplants and were managed with CNI-free approaches.

By understanding the results of this research, parents, caregivers, and healthcare professionals can gain valuable insights into the latest advancements in pediatric stem cell transplantation. This knowledge can help inform treatment decisions, improve patient outcomes, and enhance the overall quality of life for these young patients.

Understanding CNI-Free Strategies: How They Work

Child protected by medical innovation after stem cell transplant

The study, published in Pediatric Blood & Cancer, investigated the use of CNI-free strategies in 14 children who developed PRES after stem cell transplantation. The researchers aimed to describe the outcomes of these children, focusing on the effectiveness of alternative treatments for GVHD prevention and management. The study also reviewed the clinical and radiological presentation of PRES in these patients.

The core of the CNI-free approach involves:

Discontinuation of CNIs: Immediately stopping CNI treatment at the first signs of PRES.
Alternative Immunosuppression: Introducing other medications like methylprednisolone, mycophenolate mofetil, and sirolimus to prevent or treat GVHD.
Supportive Care: Managing blood pressure, preventing seizures with levetiracetam, and providing other necessary medical support.
Extracorporeal Photopheresis (ECP): Using ECP for patients with established GVHD.

The researchers closely monitored the children's neurological recovery, GVHD progression, and overall survival rates. The findings shed light on the potential benefits and challenges of CNI-free strategies in this vulnerable patient population.

The Future of Pediatric Stem Cell Transplants: Finding the Right Balance

While discontinuing CNIs often leads to neurological improvement, it's crucial to have effective alternative treatments to prevent GVHD progression. The study highlights the need for superior immune-modulating treatments that can offer the benefits of CNIs without the associated risks. Further research, especially multi-institutional prospective studies, is essential to identify the best strategies for managing GVHD and PRES in children undergoing stem cell transplantation. This collaborative effort will pave the way for safer and more effective treatments, ultimately improving the lives of these young patients and their families.

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This article is based on research published under:

DOI-LINK: 10.1002/pbc.26531, Alternate LINK

Title: Calcineurin Inhibitor-Free Strategies For Prophylaxis And Treatment Of Gvhd In Children With Posterior Reversible Encephalopathy Syndrome After Stem Cell Transplantation

Subject: Oncology

Journal: Pediatric Blood & Cancer

Publisher: Wiley

Authors: Vered Shkalim-Zemer, Osnat Konen, Yoel Levinsky, Orli Michaeli, Anat Yahel, Aviva Krauss, Isaac Yaniv, Jerry Stein

Published: 2017-04-18

Everything You Need To Know

What are Calcineurin Inhibitors (CNIs) and why are they a concern in pediatric stem cell transplants?

Calcineurin Inhibitors (CNIs) are drugs commonly used to prevent Graft-versus-Host Disease (GVHD) after stem cell transplants. However, they can cause neurological complications, such as posterior reversible encephalopathy syndrome (PRES). PRES is characterized by specific clinical and radiologic findings. Researchers are exploring CNI-free approaches to avoid these risks while still managing GVHD effectively. CNIs are used to suppress the immune system, which, while helpful in preventing GVHD, can also increase the risk of side effects like PRES.

What is Posterior Reversible Encephalopathy Syndrome (PRES) and how is it related to stem cell transplants?

PRES is a neurological condition that can occur after stem cell transplants, particularly in children. The drugs used to prevent GVHD, such as Calcineurin Inhibitors (CNIs), can contribute to its development. PRES is characterized by specific clinical and radiologic findings, meaning doctors can see signs of it on brain scans. It's often reversible with appropriate treatment, which includes discontinuing CNIs and providing supportive care. The study focuses on managing PRES in children undergoing stem cell transplants by examining the outcomes of CNI-free approaches.

Can you explain the CNI-free strategies used in managing children after stem cell transplants?

The CNI-free strategies involve a multi-pronged approach. First, Calcineurin Inhibitors (CNIs) are immediately discontinued at the first signs of Posterior Reversible Encephalopathy Syndrome (PRES). Second, alternative immunosuppressants like methylprednisolone, mycophenolate mofetil, and sirolimus are introduced to prevent or treat Graft-versus-Host Disease (GVHD). Third, supportive care, including blood pressure management and seizure prevention with levetiracetam, is provided. Finally, Extracorporeal Photopheresis (ECP) is used for patients with established GVHD. This strategy aims to minimize the risks associated with CNIs while effectively managing GVHD.

What were the key findings of the study on CNI-free approaches in pediatric stem cell transplants, and what do they mean for patient care?

The study, published in Pediatric Blood & Cancer, investigated the outcomes of children who developed PRES after stem cell transplantation using CNI-free strategies. The study described the outcomes of 14 children. The findings focused on the effectiveness of alternative treatments for Graft-versus-Host Disease (GVHD) prevention and management, including the clinical and radiological presentation of PRES in these patients. The study highlights the need for superior immune-modulating treatments that can offer the benefits of Calcineurin Inhibitors (CNIs) without the associated risks. The goal is to improve patient outcomes and the overall quality of life for these young patients.

What are the future directions for improving stem cell transplant outcomes in children?

Future research needs to focus on developing more effective and safer strategies for managing Graft-versus-Host Disease (GVHD) in children undergoing stem cell transplants. The study emphasizes the importance of finding alternative treatments that avoid the risks associated with Calcineurin Inhibitors (CNIs). Further studies, particularly multi-institutional prospective studies, are essential to identify the best approaches for managing both GVHD and Posterior Reversible Encephalopathy Syndrome (PRES). The goal is to balance effective GVHD prevention with the safety of the child, ultimately leading to improved outcomes and a better quality of life for these young patients and their families. Research should also explore the use of alternative drugs such as methylprednisolone, mycophenolate mofetil, sirolimus and Extracorporeal Photopheresis (ECP).