To aid in improving the understanding of chronic graft vs host disease (cGVHD) among pediatric patients with acute lymphoblastic leukemia (ALL) after allogeneic hematopoietic stem cell transplant (allo-HSCT), a consensus document published in the journal Frontiers in Pediatrics provides a checklist to evaluate individual risk and a treatment algorithm.

The researchers reviewed the current knowledge of pediatric cGVHD, including pathogenesis, risk factors, diagnosis, and grading. Current treatment options were also reviewed, with a focus on the counterbalance with immunosuppression and risk of relapse and infectious complications.

“We aim to present a new perspective on how management strategies can be tailored to the specific needs of individual patients and provide a framework for the personalized treatment of pediatric patients with cGVHD after HSCT for ALL to support clinicians in daily practice,” the authors wrote.

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Although the pathogenesis of cGVHD is still not fully understood, there have been advances in proposed models, such as the triphasic model that involves acute inflammation with tissue and vascular damage and dysregulated immunity and dysfunction, which are followed by dysfunctional tissue repair and the development of fibrosis. In addition, novel, potentially contributing factors such as the gut microbiome are being explored.

The researchers described validated plasma and cell biomarkers, but also highlighted that children are not small adults. “It is known that children have lower rate and perhaps different presentation of [cGVHD] compared to that seen in adults,” the authors wrote.

Known risk factors among adults developing cGVHD may also not be the same as for children. The authors conducted a retrospective study of 358 pediatric patients who underwent all-HSCT and survived relapse-free for at least 100 days. A multivariate analysis demonstrated that older donor age, female doner for a male recipient, and prior grade 2-4 acute GvHD, were identified as risk factors for cGVHD among pediatric patients. Previously defined risk factors for adults also included unrelated or mismatched donor, peripheral blood stem cells as the donor source, parity of a female donor, malignant primary disease, and the use of total body irradiation.

Diagnosis remains challenging; however, the authors indicated that it is feasible to apply the 2014 National Institutes of Health criteria to the pediatric population, and the criteria have also been adjusted for the diagnosis and staging of pulmonary GVHD for this population.

The review of the current treatment options for cGVHD in the report culminated in a section about personalized treatment. A comprehensive checklist for patient evaluation, including risk assessment and prognostic indicators, was provided.

“This walk-through checklist will provide the clinician with a summary of the patient’s status and should be used at baseline and each timepoint of clinical evaluation, helping the clinicians to identify various coexisting aspects at one glance,” the authors stated in their report.

A treatment algorithm was developed from published literature and clinical experience that translates the current treatment options into aq personalized plan for high-risk patients. The algorithm used a step-wise approach to suggest treatment according to severity of cGVHD and treatment response.

The authors concluded that “in lieu of the evidence-based data needed to inform individualized cGVHD management in pediatric patients, we hope our proposed approach that focuses on patients’ individual needs will help clinicians improve their clinical management of [cGVHD].”


Sobkowiak-Sobierajska A, Lindemans C, Sykora T, et al. Management of chronic graft-vs.-host disease in children and adolescents with ALL: present status and model for a personalised management plan. Front Pediatr. 2022;10:808103. doi: 10.3389/fped.2022.808103