Early integration of palliative care in hematology: an urgency for patients, a challenge for physicians

ABSTRACT Introduction: Early integration between palliative care and other medical specialties in the care of patients with serious illnesses is consolidating itself as good medical practice, based on scientific and ethical evidence. Despite this, palliative care is still not part of the routine care of patients with hematological diseases, even in specialized centers. Objective and method: In this article, we review the benefits and the main barriers described in the literature for early integration of hematology and palliative care. We also point out the challenges encountered in clinical practice, such as end-of-life prognosis assessment in patients with hematological diseases and management of the most common symptoms in hematology. Finally, we review models of integration between palliative care and oncology centers in outpatient and inpatient settings. Results and conclusion: Patients with hematological diseases can greatly benefit from early integration with palliative care, with improvement in symptom control, quality of life, reduction of emotional distress and the development of advanced care directives. It is necessary to make hematologists aware of the benefits of palliative care, provide adequate training for multidisciplinary teams and encourage specific studies of palliative care in patients with hematological diseases.

IL32 expression in peripheral blood CD3+ cells from myelodysplastic syndromes patients

Background: Myelodysplastic syndromes (MDS) are a heterogeneous group of disorders characterized by ineffective hematopoiesis and risk of leukemia transformation. There is evidence to suggest the participation of immune system deregulation in MDS pathogenesis. Interleukin-32 (IL-32) is a newly described multifunctional cytokine reported as an important mediator in autoimmune and inflammatory disorders. In the present study, we reported the expression of IL32 and IL32 transcript variants (α, ß, γ and δ) in peripheral blood CD3+ cells from healthy controls and MDS patients. Methods: CD3+ cells were isolated by immunomagnetic cell sorting from thirty-nine untreated MDS patients and twenty-nine healthy donors. Gene expression was evaluated by quantitative PCR. For statistical analysis, Mann­Whitney test, Kruskal-Wallis test with Dunns post test and Log-rank (Mantel-Cox) were used, as appropriate. A p value <0.05 was considered statistically significant. Results: IL32 expression and IL32 transcript variants IL32α, IL32ß, IL32γ, and IL32δ, were similar in peripheral blood CD3+ cells from healthy donors and MDS patients. Increased IL-32α expression was an independent predictor for MDS disease progression by univariate and multivariate analysis. Conclusions: We observed that IL32 expression is not differently expressed in CD3+ cells from MDS patients; nevertheless IL32α has a potential role in disease progression (AU)

SIVA, a target of p53, is downregulated in myelodysplastic syndromes

Background: SIVA is a transcriptional target of p53 that plays a potential role in the development and progression of cancer. In this study, we analyzed SIVA1 and SIVA2 expression, and its association with clinical features and TP53 and MDM2 expression in bone marrow cells from healthy donors and myelodysplastic syndrome (MDS) patients. Methods: Fifty-five untreated patients with MDS and 22 healthy donors were included. Gene expression was evaluated by quantitative PCR. For statistical analysis, Mann­Whitney test, Spearman correlation analysis and Log-rank (Mantel-Cox) were used, as appropriate. A p value <0.05 was considered statistically significant. Results: SIVA1 and SIVA2 transcripts were significantly decreased in bone marrow samples from MDS patients compared to healthy donors, and positively correlated with MDM2 and TP53 expression in MDS patients (all p < 0.05). MDM2 expression was also downregulated in bone marrow samples from MDS patients compared to healthy donors (p < 0.05). However, SIVA1, SIVA2, MDM2 and TP53 expressions did not impact on MDS outcomes. Conclusions: SIVA1 and SIVA2 transcripts are downregulated in bone marrow samples from MDS patients (AU)

Primary myelofibrosis: current therapeutic options

Primary myelofibrosis is a Philadelphia-negative myeloproliferative neoplasm characterized by clonal myeloid expansion, followed by progressive fibrous connective tissue deposition in the bone marrow, resulting in bone marrow failure. Clonal evolution can also occur, with an increased risk of transformation to acute myeloid leukemia. In addition, disabling constitutional symptoms secondary to the high circulating levels of proinflammatory cytokines and hepatosplenomegaly frequently impair quality of life. Herein the main current treatment options for primary myelofibrosis patients are discussed, contemplating disease-modifying therapeutics in addition to palliative measures, in an individualized patient-based approach

Myelodysplastic syndrome with synchronous gastric cancer: when the symptoms suggest something else

Although myelodysplastic syndromes have a clear definition in theory, the morphologic dysplasia associated with ineffective hematopoiesis may be subtle and difficult to recognize and can commonly be mimicked by systemic conditions, such as infections, autoimmune disorders, nutritional deficiencies, toxic factors and non-hematological malignancies. However, myelodysplastic syndromes may truly coexist with other systemic diseases, which can be masked when the patient's symptoms are attributed exclusively to myelodysplastic syndromes without further investigation. To better illustrate this, we herein describe two cases associated with synchronous gastric cancers...

Screening for hotspot mutations in PI3K, JAK2, FLT3 and NPM1 in patients with myelodysplastic syndromes

INTRODUCTION: Myelodysplastic syndromes encompass a heterogeneous group of clonal hematopoietic stem cell disorders characterized by ineffective hematopoiesis, refractory cytopenia and a tendency to progress toward acute myeloid leukemia. The accumulation of genetic alterations is closely associated with the progression of myelodysplastic syndromes toward acute myeloid leukemia. OBJECTIVE: To investigate the presence of mutations in the points most frequent for mutations (hotspot mutations) in phosphatidylinositol-3-kinase (PI3K), Janus kinase 2 (JAK2), FMS-like tyrosine kinase 3 (FLT3) and nucleophosmin (NPM1), which are involved in leukemia and other cancers, in a population of Brazilian MDS patients. METHODS: Fifty-one myelodysplastic syndromes patients were included in the study. According to French-American-British classification, the patients were distributed as follows: 31 with refractory anemia, 8 with refractory anemia with ringed sideroblasts, 7 with refractory anemia with excess blasts, 3 with refractory anemia with excess blasts in transformation and 2 with chronic myelomonocytic leukemia. Bone marrow samples were obtained and screened for the presence of hotspot mutations using analysis based on amplification with the polymerase chain reaction, sequencing, fragment size polymorphisms or restriction enzyme digestion. All patients were screened for mutations at the time of diagnosis, and 5 patients were also screened at the time of disease progression. RESULTS: These results show that hotspot mutations in the PI3K, JAK2, FLT3 and NPM1 genes are not common in MDS patients; nevertheless, JAK2 mutations may be present in myelodysplasia during disease progression. CONCLUSIONS: These results show that hotspot mutations in the PI3K, JAK2, FLT3 and NPM1 genes are not common in MDS patients; nevertheless, JAK2 mutations may be present in myelodysplasia during disease progression.