Correlação entre a expressão de Ikaro sem células mononucleares e o desfecho clínico em pacientes submetidos a transplante alogênico de células progenitoras hematopoéticas

• Ano de defesa: 2020
• Autor(a) principal: Pereira, Andre Domingues [UNIFESP]
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de São Paulo (UNIFESP)
• Palavras-chave em Português: Hematopoietic Progenitor Cell Transplantation; Ikaros; Graft-Versus-Host Disease; Transplante De Células Progenitoras Hematopoéticas; Doença Do Enxerto Contra O Hospedeiro
• Link de acesso: https://sucupira.capes.gov.br/sucupira/public/consultas/coleta/trabalhoConclusao/viewTrabalhoConclusao.jsf?popup=true&id_trabalho=10013806; https://hdl.handle.net/11600/64746

Introduction: Immune reconstitution after hematopoietic stem cell transplantation (HSCT) is a complex and extremely variable process. Ikaros transcription factor has an important role in hematopoiesis of several cell lines, especially in the lymphoid compartment. We hypothesized that Ikaros expression, both in the graft and in the recipient after transplant, might influence immune reconstitution and, consequently, the risk of opportunistic infections, relapse, and graft versus host disease (GVHD). Objectives: To correlate Ikaros expression both in the graft and in the recipient’s peripheral blood (PB) after engraftment with the transplant outcomes. Patients and methods: Samples were collected from the graft and from the PB of the recipient 3 weeks after neutrophil recovery. Real time polymerase chain reaction (RT-PCR) was performed for analysis of absolute and relative Ikaros expression. 66 patients were included. Median age was 52 years (18-80), 55% of patients were male, and most (58%) had acute leukemia. Donors were haploidentical in 48% of cases, matched related identical in 29% and matched unrelated in 23%. Most patients (82%) received reduced-intensity conditioning regimens. Median follow-up was 18 months (10-43 months). Results: There was no association between Ikaros expression and the risk of acute GVHD, relapse or mortality. However, a significant association was observed in the risk of chronic GVHD. Higher Ikaros expression in the graft was associated with a significantly higher cumulative incidence (CI) of moderate/severe of moderate to severe chronic GVHD (according to National Institute of Health - NIH classification) at two years chronic (71% vs. 38% for patients with lower expression, respectively, P=0.04). Higher Ikaros expression in the recipient’s PB 3 weeks after engraftment was also associated with a significantly higher risk of moderate/severe chronic GVHD (68% vs. 24%, respectively, P=0.006). Conclusions: Ikaros expression in the graft and in the PB of the recipient after transplant was associated with a higher risk of moderate/severe chronic GVHD. Ikaros expression could be evaluated in larger and prospective trials as a potential biomarker for chronic GVHD.