CAR-T cell therapies have been recognized as one of the most advanced and efficient strategies to treat patients with hematologic malignancies. However, similar results have not been observed for the treatment of solid tumors. One of the explanations is the fact that tumors have extremely hostile microenvironments for the infiltration and effector activity of T-cells, mainly due to the presence of highly suppressive cytokines, hypoxia, and reactive oxygen species. Taking advantage of cytokines functionally, new fourth-generation CAR constructs have been developed to target tumor cells and additionally release cytokines that can contribute to the cytotoxicity of T-cells. The manufacturing process, including the use of cytokines in the expansion and differentiation of T cells, is also discussed. Finally, the clinical aspects and the influence of cytokines on the clinical condition of patients, such as cytokine release syndrome, who receive treatment with CAR-T cells are addressed. Therefore, this review aims to highlight how important cytokines are as one of the major players of cell therapy.

Background: Steroid-refractory acute graft-vs.-host disease (SR-aGVHD) is a complication of allogeneic hematopoietic stem cell transplantation with a dismal prognosis and for which there is no consensus-based second-line therapy. Ruxolitinib is not easily accessible in many countries. A possible therapy is the administration of mesenchymal stromal cells (MSCs). Methods: In this retrospective study, 52 patients with severe SR-aGVHD were treated with MSCs from umbilical cord (UC-MSCs) in nine institutions. Results: The median (range) age was 12.5 (0.3–65) years and the mean ± SD dose (×106/kg) was 4.73 ± 1.3 per infusion (median of four infusions). Overall (OR) and complete response (CR) rates on day 28 were 63.5% and 36.6%, respectively. Children (n = 35) had better OR (71.5% vs. 47.1%, p = 0.12), CR (48.6% vs. 11.8%, p = 0.03), overall survival (p = 0.0006), and relapse-free survival (p = 0.0014) than adults (n = 17). Acute adverse events (all of them mild or moderate) were detected in 32.7% of patients, with no significant difference in children and adult groups (p = 1.0). Conclusions: UC-MSCs are a feasible alternative therapy for SR-aGVHD, especially in children. The safety profile is favorable.

THE BRAZILIAN SOCIETY FOR BLOOD AND MARROW TRANSPLANTATION (SBTMO) PRESENTS THE BRAZILIAN GUIDELINES ON HEMATOPOIETIC STEM CELL TRANSPLANTATION

Objetivo: Esse trabalho descreveu um caso inédito em literatura de descompensação hepática pela doença falciforme em paciente já transplantado de medula óssea que levou a necessidade de transplante hepático Detalhamento do caso: Paciente de 51 anos, transplantado com células tronco progenitoras em razão de doença falciforme aos 38 anos de idade, sabidamente portador de hepatopatia crônica por hemossiderose com altos níveis de ferritina e saturação de transferrina, inicia descompensação do quadro hepático após procedimento dentário com queda do hematócrito em exames sucessivos. Após introdução de terapêutica adequada para prevenção de peritonite bacteriana espontânea apresenta nova descompensação com suspeita de hepatite aguda medicamentosa, necessitando de internação em UTI e transplante de fígado. Após transplante hepático paciente evoluiu com melhora dos níveis de saturação de transferrina e ferritina, sem necessidade de uso de quelantes de ferro. Considerações finais: O transplante de células progenitoras para tratamento da DF é uma opção de tratamento curativa disponível, porém não é capaz de prevenir complicações inerentes às comorbidades apresentadas previamente ao procedimento, como a progressão de hepatopatia crônica culminando em falência hepática.