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Objectives: This review aims to evaluate the impact of obesity on Bone Marrow Transplant (BMT) recipients diagnosed with Graft-Versus-Host Disease (GVHD), in different age groups. Material and methods: A search was carried out on the PubMed and Virtual Health Library platforms, using the descriptors “Graft-versus-Host Disease”and “Obesity”. Articles in English published between 2011 and 2021 were selected. Rayyan® and Microsoft Excel® software were used to select manuscripts and interpret results. Results: 47 articles were found. 7 duplicates and 32 articles that did not focus on the relationship between obesity and GvHD were removed. 8 articles were included in this study, of which 2 are meta-analyses and 6 are retrospective cohorts. 24.9% of BMT recipients are obese (Pereira et al., 2015). Fuji et al. (2015) points out that the three main prognostic nutritional factors in BMT are obesity, diabetes mellitus and liver dysfunction. In children, the meta-analysis by Yaseri et al. (2021) showed a higher prevalence of acute GvHD when compared to non-obese children (OR = 2.13, 95% CI: 1.5‒3.02, p < 0.001); while the work by Barker et al. (2011) showed a 1.55 times higher risk (95% CI: 1.00‒2.41; p = 0.05). The meta-analysis by Nakao et al. (2014), without age group restriction, obtained a relative risk of 1,186 (95% CI: 1,072–1,312) of acute GvHD in overweight individuals, compared to non-overweight patients. Another important criterion for discussion is acute post-BMT hyperglycemia, which is associated with a higher risk of acute GvHD, infection and mortality post-BMT (Fuji et al., 2015). In obese individuals, however, the study by Gebremedhin et al. (2013) concluded that, in these individuals, unlike non-obese individuals, severe hyperglycemia, developed in 30.5% of patients, did not significantly affect the risk of acute GvHD (none of the 34 obese subjects developed GvHD). The only study addressing geriatric obesity regarding the risk of GvHD states that there is no difference in the incidence of acute and chronic GvHD between obese and non-obese elderly people, one year after BMT (Voshtina et al., 2019). Discussion: Obesity is a global problem, and 12.5% of individuals are obese (PAHO, 2024). The studies retrieved indicate that there is a higher prevalence of this comorbidity in BMT recipients than in the general population. There are important variances in the values obtained for the relationship between obesity in BMT recipients and the development of GvHD, with one of the main factors involved in this difference being the age group of the patients. Acute hyperglycemia is harmful to newly transplanted patients, increasing the risk of GVHD, infections and BMT complications, and is intrinsically related to oxidative stress proposed by the release of chemokines. The study of a possible protective factor in obesity against the damage caused by acute hyperglycemia, especially regarding the risk of developing acute GvHD, deserves special attention from Onco-hematology. Conclusion: Obesity is a very likely and well-founded risk factor for the development of GvHD, and its prevalence is increased in BMT recipients. The care of obese patients, in specialized BMT services, involves increased attention to the risk of GvHD, which reduces quality of life, increasing the risk of infections and general mortality.

Objectives: This review aims to analyze the benefits of bone marrow transplantation (BMT) in patients positive for the Human Immunodeficiency Virus (HIV) with hematological malignancies and to understand the limitations of BMT in this scenario, as well as to obtain perspectives on the long-term therapeutic potential of the procedure. Materials and methods: This is a literature review conducted by analyzing articles published between 2008 and 2024, written in English, obtained through the PubMed and BVS databases. The descriptors used are in accordance with the Health Sciences Descriptors System (DeCS), being: “Stem cell transplantation”, “Bone marrow transplantation”, “AIDS-related lymphoma” and “HIV-related lymphoma”. Results: The reality of patients with HIV infection was revolutionized with the advent of Highly Active Antiretroviral Therapy (HAART), which increased their survival and reduced the prevalence of opportunistic diseases. However, the incidence of Hodgkin's lymphoma (HL) and non-Hodgkin's lymphoma (NHL) remains increased in HIV+ patients. In this sense, before the advent of HAART, stem cell transplantation was not feasible for HIV+ patients, due to the post-transplant course being characterized by multiple opportunistic infections and high rates of neoplastic relapse. After the emergence of HAART, mortality due to infections was reduced, but lymphoma control remains a challenge, due to drug interactions. Selected articles showed that HAART patients with HL and NHL undergoing chemotherapy followed by BMT had similar complete remission and survival rates to HIV-negative patients, with progression-free survival ranging from 49.5-85% and overall survival from 63.5-81%. This variation is due to different chemotherapy regimens, patient selection criteria, and viral load. Allogeneic hematopoietic stem cell transplantation in HIV+, despite the not so vast experimental basis in the literature, can be performed safely and lead to long-lasting remissions, as well as having a remote potential to eradicate HIV infection, with 6 cases already reported in the literature. Furthermore, transplantation-related toxicity, event-free survival, relapse rate, and overall survival of HIV+ patients were similar to those of HIV-negative patients, but there is a higher risk of infection. Discussion: The review pointed out clear benefits of allogeneic hematopoietic stem cell transplantation in HIV-positive patients, significantly increasing the overall survival of this group, with results similar to those of HIV-negative patients (despite having shown greater susceptibility to infections). In addition, it is noteworthy that this procedure was only possible after the development of HAART, which allowed for greater control of the infection. However, to achieve these benefits, the use of prophylactic and supportive measures is necessary, in addition to performing the procedure in specialized centers. Conclusion: Allogeneic BMT in HIV-positive patients has proven beneficial for both the treatment of lymphoma. Thus, this procedure is a therapeutic possibility for advanced lymphomas in this group of patients in tertiary care centers, with due care directed to the HIV+ patient and with hematological neoplasia.

Objetivo: Esta revisão busca correlacionar a importância do microambiente tumoral (TME) na ocorrência de leucemias crônicas, com enfoque na leucemia linfocítica crônica (LLC), objetivando compreender de que forma tais condições impactam na patogênese dessa doença e na sua resposta aos tratamentos. Materiais e métodos: Trata-se de uma revisão de literatura realizada pela análise de artigos publicados entre 2021 e 2024, escritos na língua inglesa, obtidos através da base de dados PubMed e EMBASE. Os descritores utilizados na pesquisa estão de acordo com o Sistema de Descritores em Ciências da Saúde (DeCS) e são, respectivamente, “tumor microenvironment”e “Chronic Lymphocytic Leukemia”. Resultados: A LLC depende fortemente da interação dinâmica entre as células leucêmicas e o TME, pois este fornece suporte para as células leucêmicas por meio de sinais de proliferação e sobrevivência, criando um nicho que protege as células tumorais, contribuindo para a resistência ao tratamento, progressão da doença e recidivas. As células estromais mesenquimais são elementos-chave no TME, associadas à progressão do tumor e mau prognóstico, pois ajudam a prevenir a apoptose espontânea das células tumorais. As células endoteliais e as dendríticas contribuem para a ativação, resistência ao tratamento e sobrevivência das células malignas. Já os macrófagos podem, a partir do TME, induzir a tolerância imunológica ou iniciar uma resposta imune potente contra as células tumorais, influenciando na resistência ao tratamento. Os neutrófilos na LCC têm migração prejudicada e deficiência na fagocitose e na atividade bactericida. Além disso, podem se polarizar em fenótipos antitumorais ou pró-tumorais, dependendo do TME, contribuindo para angiogênese e metástases. A evasão imune na LLC também é influenciada pela baixa atividade de células T CD8+ e células Natural Killer (NK) contra as células leucêmicas, enquanto a alta frequência de células T reguladoras está associada à supressão das respostas imunes antitumorais, maior crescimento tumoral e à um prognóstico ruim. Ademais, a quinase LYN, moduladora importante da homeostase das células B, está aberrantemente ativada na LLC, promovendo maior agressividade e resistência à apoptose das células leucêmicas. Discussão: O TME da LLC organiza um complexo sistema celular e molecular que contribui para a evasão da imunidade antitumoral e a sobrevivência das células leucêmicas. Pacientes com LLC frequentemente apresentam respostas imunes ineficazes devido à disfunção induzida pelas células malignas, com função prejudicada de células dendríticas, células NK, células T citotóxicas e macrófagos. Além disso, há modificações significativas na resposta imune humoral, contribuindo para a evasão do tumor. Conclusão: A compreensão dessas interações tem implicações terapêuticas importantes, por isso, há maior interesse em direcionar o tratamento para o TME, a fim de torná-lo mais eficaz, combinando diferentes aspectos do TME na mesma terapia. Embora os inibidores de sinalização do receptor de células B, como o ibrutinibe e o venetoclax tenham melhorado os resultados do tratamento ao interferir nessas interações entre células tumorais e TME, a resistência crescente aos medicamentos e as limitações das imunoterapias atuais destacam a necessidade de um entendimento mais profundo das interações entre LLC e TME para superar tais empecilhos e melhorar os resultados terapêuticos para os pacientes.

Objetivos: Avaliar os estudos mais recentes atinentes à utilização de nanomateriais no contexto de uma terapia dirigida contra a leucemia. Materiais e métodos: Trata-se de uma revisão de literatura, de natureza descritiva, frente à análise de artigos publicados, entre os anos de 2020 e 2024, nas bases de dados PubMed e Cell Press Journals. Para isso, utilizou-se os descritores em inglês “nanomaterials”, “target therapy”e “leukemia”. Após passar pelos critérios de inclusão e exclusão, o estudo resultou em uma amostra total de cinco artigos de revisão selecionados: três (3) do PubMed e dois (2) do Cell Press Journals. Resultados: As terapias atuais evidenciadas no tratamento da leucemia abrangem, principalmente, a quimioterapia, a radioterapia, o transplante de células-tronco, a imunoterapia e a terapia direcionada. Nesse aspecto, o surgimento de novas interfaces terapêuticas – como o uso de nanomateriais – representa um avanço proeminente para a melhoria dos resultados terapêuticos. Esses materiais são compostos por partículas que possuem tamanho inferior a 1000 nm e detêm propriedades físicas, químicas e biológicas singulares, as quais conferem reatividade aprimorada, maior absorção celular e alta relação área de superfície/volume. Os estudos pontuam, quanto ao mecanismo de ação dos nanomateriais, a sua reverência em possibilitar a administração direcionada de medicamentos. Essas nanopartículas podem atuar como ligantes ou anticorpos que se ligam, de forma seletiva, às células cancerígenas e administram, no local do tumor, medicamentos de forma direta. Ainda quanto à farmacodinâmica dessas partículas, os nanomateriais também podem liberar medicamentos de forma controlada, podendo prolongar a ação de quimioterápicos. Essas partículas conseguem, também, aumentar a absorção e o transporte de medicamentos através das membranas celulares, auxiliando no combate à resistência a múltiplos medicamentos. Discussão: O uso de nanomateriais em terapias dirigidas à leucemia é de suma importância, tendo em vista os seus benefícios para a maior eficácia terapêutica. Uma abordagem inovadora utiliza nanopartículas de ouro como carreadores de doxorrubicina, um medicamento quimioterápico. Ao serem ativadas por laser, essas nanopartículas liberam esse fármaco de forma controlada, direcionando-o para células cancerígenas, permitindo, assim, um tratamento mais personalizado. Fora isso, esses materiais também podem aumentar a sensibilidade e a especificidade de exames de imagem, como a RM e a TC. As propriedades fluorescentes, magnéticas e ópticas desses nanomateriais permitem a visualização direta e indireta de tumores. Por exemplo, nanopartículas de ouro funcionalizadas com peptídeos específicos permitem a visualização de células cancerígenas por TC. Contudo, empecilhos podem ser notados quanto à aplicabilidade do uso das nanopartículas no tratamento da leucemia, haja vista que a síntese de nanomateriais com características uniformes e reprodutíveis é complexa e pode ser difícil de escalar para produção em massa. Conclusão: Portanto, a nanotecnologia empregada na terapia direcionada à leucemia pode trazer oportunidades e aplicações específicas. Atrelada a isso, a administração de fármacos nanomédicos tem forte potencial terapêutico e desempenha funções farmacodinâmicas e farmacocinéticas importantes para a maximização de tecnologias terapêuticas emergentes no combate à leucemia.

Introduction/objectives: Sickle cell disease (SCD) is the most common monogenic blood disorder worldwide, causing reduced life expectancy to the patients. The innovative CRISPR-Cas9 gene-editing technology, pioneered by Jennifer Doudna and Emmanuelle Charpentier, has emerged as a potential curative treatments for SCD. This review aims to comprehensively explore the latest advancements in CRISPR-Cas9 for SCD treatment. Methods: This is a literature review carried out through the analysis of articles published between 2016 and 2024 obtained through a search in the PubMed database. The descriptors used were: (Sickle cell disease) AND (CRISPR). A total of 12 articles were selected based on these criteria. Results: The development and regulatory approvals of therapeutic CRISPR-Cas9 for patients with SCD has been crucial in improving curative treatment options. This gene therapy involves targeting the BCL11A erythroid-specific enhancer to induce the expression of fetal hemoglobin (HbF), which can alleviate the clinical manifestations of this hemoglobinopathy. This approach aims to correct the genetic defect at its source, offering a potential functional cure for SCD. Discussion: Sickle cell disease (SCD) is a group of inherited red blood cell disorders characterized by the production of abnormal hemoglobin, specifically hemoglobin S (HbS). This genetic defect is caused by a point mutation in the β-globin gene on chromosome 11, and leads the hemoglobin molecules to polymerize under low oxygen conditions, resulting in the deformation of red blood cells into a rigid, sickle shape. Besides hemoglobin polymerization, the pathophysiology of SCD involves: vaso-occlusive crisis, hemolytic anemia, splenic dysfunction and organ damage. This can result in ischemia, tissue damage, and severe pain. Chronic vaso-occlusion and microinfarctions can cause damage to various organs, including the liver, kidneys, lungs, and bones. SCD is managed through a combination of symptomatic treatments, disease-modifying therapies, but curative treatment options for SCD remain very limited. Symptomatic treatments include hydroxyurea, which increases fetal hemoglobin (HbF) levels, reducing vaso-occlusive crises; L-glutamine, Voxelotor and Crizanlizumab. The only established curative treatment was allogeneic hematopoietic stem cell transplantation (HSCT), but this option is limited by donor availability and risks of graft-versus-host disease. Therefore, CRISPR-Cas9 technology has a great potential as a curative treatment of SCD, once his approach has shown promising results in clinical trials, with patients achieving high levels of HbF and significant clinical improvements, including the elimination of vaso-occlusive episodes. These studies led to important regulatory agents approvals in Europe and the USA. Conclusion: CRISPR-Cas9 therapy has a great potential to provide a durable and potentially curative treatment for SCD. By reactivating HbF production, CRISPR-Cas9 can mitigate the pathophysiological effects of HbS polymerization, thereby reducing the frequency of vaso-occlusive crises and improving overall hematologic parameters. This represents a significant advancement over traditional treatments, which primarily focus on symptom management and reducing complications, leading to significant clinical benefits and offering a promising therapeutic avenue for this debilitating disease.