Chronic graft-versus-host-disease

Chronic GvHD is a major cause of non-relapse morbidity and mortality after hematopoietic cell transplantation. Its incidence has increased due to more frequent use of unrelated and/or mismatched donors, reduced intensity conditioning regimens or intensified regimens and PBSC grafts. The first-line therapy for chronic GvHD is systemic corticosteroids associated with either CNI or sirolimus, as a steroid sparing agent. Since children are more susceptible to the long-term steroid side effects, development of steroid-free strategies for front-line therapy is crucial. Sirolimus seems to be an interesting choice due to its capacity of inhibiting T-cells preserving the Tregs cells and antifibrotic, antineoplastic and antiviral activities. FAM regimen (Fluticasone, Azitromycin and Montelucaste) is recommended in combination with systemic steroids for initial treatment of bronchiolitis obliterans. For steroid-refractory chronic GvHD, ruxolitinib is the standard of care, while extracorporeal photopheresis can be combined for better results, however treatment costs are limitations. Extracorporeal photopheresis, treatment that preserves graft-versus-leukemia effect due to its steroid sparing and immunomodulatory actions, and mesenchymal stem cells, another non-pharmacological strategy that can be combined with the options mentioned above in severe chronic GvHD. Since access to novel drugs and extracorporeal photopheresis or mesenchymal stem cells is tough, other options approved for the third line and beyond are ibrutinib, belumosudil and axatilimab. Conventional agents could be used such as imatinib, low dose-MTX, rituximab, however the expected response rates are lower. We reviewed clinical studies and published recommendations on pediatric chronic GVHD that were presented in debate rounds with GvHD experts of the Pediatric group of the Sociedade Brasileira de Terapia Celular e Transplante de Medula Óssea (SBTMO). The goal of this consensus is to standardize the prophylaxis, diagnosis, grading and treatment of chronic GvHD among Brazilian pediatric HCT centers, to improve post-transplant outcomes.