Management of Chronic Graft-vs.-Host Disease in Children and Adolescents With ALL: Present Status and Model for a
Agnieszka Sobkowiak-Sobierajska1, Caroline Lindemans2,3, Tomas Sykora4
1Department of Pediatric Oncology, Hematology and Transplantology, Poznan University of Medical Sciences, Poznan, Poland.
Insights
This review details managing chronic graft-vs-host disease (cGvHD) in children post-hematopoietic stem cell transplant (HSCT) for acute lymphoblastic leukemia (ALL). It covers epidemiology, pathogenesis, risk factors, diagnosis, and treatment options, emphasizing personalized care.
Area of Science:
- Pediatric Hematology/Oncology
- Immunology
- Transplantation Medicine
Background:
- Chronic graft-vs-host disease (cGvHD) is a significant complication following allogeneic hematopoietic stem cell transplantation (HSCT).
- Management of cGvHD in pediatric patients undergoing HSCT for acute lymphoblastic leukemia (ALL) presents unique challenges.
- Current treatment strategies require optimization to balance efficacy with risks of infection and relapse.
Purpose of the Study:
- To provide a comprehensive review of current practices for managing pediatric cGvHD after HSCT for ALL.
- To discuss advances in understanding cGvHD pathogenesis, risk factors, and prevention.
- To outline diagnostic criteria, treatment options, and personalized management approaches.
Main Methods:
- Review of current literature and clinical practice guidelines.
- Analysis of epidemiological data and risk factors for cGvHD.
- Evaluation of diagnostic criteria (NIH 2014) and therapeutic interventions, including novel agents and immunomodulatory approaches.
- Examination of response assessment, treatment tapering, and anti-infectious prophylaxis strategies.
Main Results:
- cGvHD affects pediatric patients post-HSCT for ALL, with evolving understanding of its pathogenesis and risk factors.
- Current management involves topical therapies, tyrosine kinase inhibitors, and immunomodulatory strategies, requiring careful balancing of immunosuppression and immune reconstitution.
- Personalized risk evaluation and treatment algorithms are crucial for optimizing outcomes and minimizing complications.
Conclusions:
- A holistic approach and individualized risk assessment are essential for managing pediatric cGvHD.
- Personalized management plans, informed by risk evaluation and treatment algorithms, can improve outcomes for high-risk patients.
- Further research is needed to refine prevention, diagnosis, and treatment strategies for pediatric cGvHD.
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.
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