Management of Chronic Graft-vs.-Host Disease in Children and Adolescents With ALL: Present Status and Model for a Personalised Management Plan

Abstract

Herein we review current practice regarding the management of chronic graft-vs.-host disease (cGvHD) in paediatric patients after allogeneic haematopoietic stem cell transplantation (HSCT) for acute lymphoblastic leukaemia (ALL). Topics covered include: (i) the epidemiology of cGvHD; (ii) an overview of advances in our understanding cGvHD pathogenesis; (iii) current knowledge regarding risk factors for cGvHD and prevention strategies complemented by biomarkers; (iii) the paediatric aspects of the 2014 National Institutes for Health-defined diagnosis and grading of cGvHD; and (iv) current options for cGvHD treatment. We cover topical therapy and newly approved tyrosine kinase inhibitors, emphasising the use of immunomodulatory approaches in the context of the delicate counterbalance between immunosuppression and immune reconstitution as well as risks of relapse and infectious complications. We examine real-world approaches of response assessment and tapering schedules of treatment. Furthermore, we report on the optimal timepoints for therapeutic interventions and changes in relation to immune reconstitution and risk of relapse/infection. Additionally, we review the different options for anti-infectious prophylaxis. Finally, we put forth a theory of a holistic view of paediatric cGvHD and its associated manifestations and propose a checklist for individualised risk evaluation with aggregated considerations including site-specific cGvHD evaluation with attention to each individual's GvHD history, previous medical history, comorbidities, and personal tolerance and psychosocial circumstances. To complement this checklist, we present a treatment algorithm using representative patients to inform the personalised management plans for patients with cGvHD after HSCT for ALL who are at high risk of relapse.

Mesenchymal Stem Cell-Derived Secretome: A Potential Therapeutic Option for Autoimmune and Immune-Mediated Inflammatory Diseases

“…It is based on the fact that the host appears to non-self to the graft and so it can stimulate antigenically, employing a broad spectrum of immune mechanisms. GvHD is classified into acute and chronic types [ 143 ]. The chronic form frequently mimics autoimmune diseases.…”

Cardiovascular morbidity following conventional therapy versus allogeneic hematopoietic stem cell transplantation after childhood, adolescent, and young adult leukemia in Finland

“…It has been stated that cytomegalovirus (CMV) reactivation after aHSCT leads to elevated mortality. 40 Furthermore, the association of acute GVHD (aGVHD) with elevated mortality has been demonstrated especially concerning grades III and IV aGVHD in previous reports. 41 Unfortunately, we had no access to information on the patients' toxicity scores, nor to infections during primary treatment or at aHSCT.…”

“…Unfortunately, reliable data on antimicrobial preventive measures, such as the CMV prophylaxis and differences in prophylactic antimicrobial medications, were not available for this study. It has been stated that cytomegalovirus (CMV) reactivation after aHSCT leads to elevated mortality 40 . Furthermore, the association of acute GVHD (aGVHD) with elevated mortality has been demonstrated especially concerning grades III and IV aGVHD in previous reports 41 .…”

Translating Precision Health for Pediatrics: A Scoping Review

“…The challenges related to the health system and the provider were (1) gaps in provider comfort; (2) gaps in clinical evidence; and (3) gaps in the system capacity. A key barrier to adopting precision health interventions was clinicians' lack of comfort with precision health (e.g., interpretation of findings, treatment selection, and awareness of available resources) [20,22,24,38,59,61,65,66,77,[81][82][83]. The uncertain clinical significance of some findings and the limited guidelines related to the therapy selection [21,22,34,[49][50][51][52][53]57,66,69,76,79,81,84] pose additional challenges for providers seeking to integrate genomic information into their care plans.…”