RESUMO
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.
RESUMO
Graft-versus-host disease (GVHD) is a major factor contributing to mortality and morbidity after allogeneic stem-cell transplantation. Because of the small number of results from well designed, large-scale, clinical studies there is considerable variability in the prevention and treatment of GVHD worldwide. In 2014, to standardise treatment approaches the European Society of Blood and Marrow Transplantation published recommendations on the management of GVHD in the setting of HLA-identical sibling or unrelated donor transplantation in adult patients with haematological malignancies. Here we update these recommendations including the results of study published after 2014. Evidence was searched in three steps: first, a widespread scan of published trials, meta-analyses, and systematic reviews; second, expert opinion was added for specific issues following several rounds of debate; and third, a refined search to target debated or rapidly updating issues. On the basis of this evidence and the 2014 recommendations, five members of the EBMT Transplant Complications Working Party created 38 statements on GVHD prophylaxis, drug management, and treatment of acute and chronic GVHD. Subsequently, they created the EBMT GVHD management recommendation expert panel by recruiting 20 experts with expertise in GVHD management. An email-based, two-round Delphi panel approach was used to manage the consensus. Modified National Comprehensive Cancer Network categories for evidence and consensus were applied to the approved statements. We reached 100% consensus for 29 recommendations and 95% consensus for nine recommendations. Key updates to these recommendations include a broader use of rabbit anti-T-cell globulin; lower steroid doses for the management of grade 2 acute GVHD with isolated skin or upper gastrointestinal tract manifestations; fluticasone, azithromycin, and montelukast should be used for bronchiolitis obliterans syndrome; and the addition of newer treatment options for resteroid-refractory acute and chronic GVHD. In addition, we discuss specific aspects of GVHD prophylaxis and management in the setting of haploidentical transplantation and in paediatric patients, but no formal recommendations on those procedures have been provided in this Review. The European Society of Blood and Marrow Transplantation proposes to use these recommendations as a basis for the routine management of GVHD during stem-cell transplantation.