Hematopoietic cell transplantation in pediatric patients with acute leukemias or myelodysplastic syndrome using unrelated adult or umbilical cord blood donors in Brazil

The best way to manage acute leukemia relapse after HCT is to prevent it, buying time for GVL with immunomodulation and, if no GVHD between days +60 and + 90, prophylactic DLI can be indicate for very high or high risk patients. Short-term low dose of cyclosporine or methotrexate can add safety to pro-DLI, particularly after mismatched or unrelated transplantation. Maintenance with imatinib or dastinib, recommended for Ph-positive ALL, with sorafenib, for FLT3-ITD AML, or azacitidine, for myelodysplastic syndrome patients, can be effective in reducing relapse rates. However, target agent maintenance can add toxicity, depends on patient adherence and demands physician experience to know when is safe to start, how adjust the dose according individual tolerance after transplant and to detect undesirable drug interactions. The second step to avoid hematological relapse is preemptive approach guided by measurable residual disease or mixed chimerism. In patients off immunosuppression, chemotherapy followed by DLI is a useful strategy, and if no response, interferon alpha can be associated to enhance GVL. Target-specific agents can be start at this point either. After relapse, antigen-directed therapy with blinatumumab for CD19 ALL, inotuzumab for CD22 ALL are excellent options to induce MRD negativity and facilitate HCT. Disadvantages of new immunotherapies are: high incidence of VOD with inotuzumab and gemtuzumab; lower response in patients with high leukemia burden or concurrent extramedullary relapse; necessity of consolidation with HCT after a bridging therapy with BiTE and probably with CAR-T cell therapy also. It is important to realize that if remission after chemotherapy is associated with the development of GVHD, then there may be limited benefit (and possibly harm) in consolidating with any kind of cellular therapy. However, for patients who achieved remission without GVHD, either DLI or second transplant can be recommend. Further studies are necessary to determine at which point each strategy might yield the best results.

Section: Introductionmentioning

confidence: 89%

Prevention and Management of Relapse of Acute Leukemia and Myelodysplastic Syndrome After Allogeneic Hematopoietic Cell Transplantation in Pediatric Patients

Tavares

Pelegrina²

2021

“…GVHD prophylaxis comprised CsA and MTX in 97% plus in-vivo T-depletion in 100% of cases. Tavares and cols 41 , in turn, showed incidences of grade III-IV aGVHD of 18%, 13% and 17% and of moderate/severe cGVHD of 8%, 22% and 4% after MUD (n = 95), MMUD (n = 47) and umbilical cord blood (UCB) (n= 70) transplants, respectively, in patients undergoing HSCT for acute leukemia and myelodysplastic syndrome. In this study, GVHD prophylaxis consisted of a calcineurin inhibitor (CNI) + MMF or steroids in 90% of UCB transplants and of a CNI + MTX in 80% and 89% of MUD and MMUD transplants, respectively.…”

Section: Prophylaxis and Biomarkers Of Gvhd In Pediatric Patientsmentioning

confidence: 99%

Acute and Chronic Graft-Versus-Host-Disease – A Focus on Pediatric Patients

Macedo¹,

Garcia

Gouveia

et al. 2021

Graft-versus-host disease (GVHD), either in its acute or chronic form, is the main contributory factor for morbidity and non-relapse mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Recent advancements in the classification of this disease, with better applicability and reproducibility of standardized criteria, coupled with improvements in the management of steroid-refractory or resistant cases, have led to promising results. In 2020, the Brazilian Group for Pediatric Bone Marrow Transplantation of the Brazilian Society for Blood and Marrow Transplantation and Cellular Therapy (SBTMO) convened a task force to provide updated, evidence-based guidance for the diagnosis, classification, staging, prophylaxis, and treatment of GVHD, with a focus on the pediatric population, the results of which are presented here.

“…In children, bone marrow is preferable in comparison to peripheral blood (PB) as stem-cell source, given the higher extensive chronic GVHD and transplant-related mortality (TRM) with the use of PB stem cells (8,18) . The use of Umbilical Cord Blood (UCB) is associated with higher TRM in Brazil and should only be used by centers experienced with this stem cell source (19) .…”

Section: Which Is the Best Donor And Stem-cell Source?mentioning

confidence: 99%

Hematopoietic Stem Cell Transplantation for Pediatric Acute Lymphoblastic Leukemia - SBTMO/SOPOBE 2020 Consensus Guidelines

Daudt

Macedo

Guimarães

et al. 2021

Self Cite

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative approach to children and adolescents with high-risk acute lymphoblastic leukemia (ALL) at diagnosis or relapsed disease. Nonetheless, despite the graft versus leukemia (GVL) effect, treatment-related morbidity and mortality remains a major challenge. Moreover, the significant heterogeneity of the available data on the selection of patients, type of conditioning regimen, and type of donor hampers any definitive conclusions in the pediatric population. In 2020, the Brazilian Group for Pediatric Bone Marrow Transplantation of the Brazilian Society of Bone Marrow Transplantation and Cellular Therapy (SBTMO) and the Brazilian Society for Pediatric Oncology (SOBOPE) convened a task force to provide general guidance on HSCT for childhood ALL to providing evidence-based guidance for the appropriate management of this disease.