The role of hematopoietic stem cell transplantation in the elderly patient with acute myeloid leukaemia

Older adults with Acute Myeloid Leukaemia (AML), when compared to younger patients with the same disease, have a poor prognosis and represent a discrete population in terms of disease biology, treatment-related complications, and overall outcome. As a result, older patients require distinctive management approaches. For 85%-95% of older AML patients, any therapy ultimately will be purely palliative. No randomized trial has ever demonstrated that any amount of post-remission therapy in older AML patients provides better outcomes than no post-remission therapy. The only studies demonstrating that long-term Disease Free Survival (DFS) is possible in older AML patients have included remission induction and post-remission therapy. For these reasons alternative post-remission strategies, including autologous or allogeneic transplantation have been explored also in people over sixty considered fit for aggressive therapy. Up to now the data available from clinical trials suggest that the stem cell transplant procedure is promising, and can lead to long-term survival, but it is feasible only in a minority of fit elderly patients. The main limits of Autologous Stem Cell Transplantation (ASCT) are represented by the low percentage of patients able to mobilize a sufficient amount of stem cells and by the still high relapse incidence after ASCT, especially in those with poor prognostic factors; for these patients the allogeneic transplant procedure, by using non myeloablative conditioning regimens, could offer a better chance of cure, thanks to the Graft versus Leukemia (GVL) effect, but there are no prospective trials showing the superiority of any transplant approach over conventional treatment in this subset of patients. Pacientes idosos com leucemia mielóide aguda (LMA), quando comparados com pacientes jovens com a mesma doença, apresentam prognóstico pobre e representam uma população particular em termos biológicos, complicações relacionadas ao tratamento e evolução clínica. Como resultado de tudo isto, o paciente idoso requer manuseio distinto. Para 85%-95% dos pacientes idosos a abordagem terapêutica será finalmente apenas paliativa. Nenhum estudo randomizado demonstrou qualquer vantagem de qualquer terapêutica na fase pós-remissão. Os únicos estudos que mostraram alguma vantagem em termos de sobrevida livre de doença em pacientes idosos portadores de LMA incluíram juntas as fases de indução e consolidação da remissão. Por estas razões, estratégias terapêuticas alternativas pós-remissão, incluindo transplante autólogo ou alogênico, têm sido exploradoras também em pacientes acima de 60 anos com boa performance status para as terapias de alta dose. Até agora, os dados disponíveis dos estudos clínicos sugerem que o procedimento usando célula-tronco é promissor e pode levar a sobrevida de longo prazo, porém factível apenas em uma minoria de pacientes idosos. Os principais limites para o transplante autólogo são representados pela baixa porcentagem de pacientes capazes de mobilizar suficiente quantidade de células-tronco e pela, ainda, alta incidência de recidiva após o transplante, principalmente em pacientes de fatores de mau prognóstico. Para o transplante alogênico, o uso de regimes de intensidade reduzida pode oferecer uma melhor oportunidade de cura graças ao efeito enxerto versus leucemia. Porém, não existem estudos clínicos comprovando a superioridade de qualquer modalidade de transplante em relação à terapia convencional

Bone Marrow Adipose Tissue

Bone marrow (BM) acts as a dynamic organ within the bone cavity, responsible for hematopoiesis, skeletal remodeling, and immune system control. Bone marrow adipose tissue (BMAT) was long simply considered a filler of space, but now it is known that it instead constitutes an essential element of the BM microenvironment that participates in homeostasis, influences bone health and bone remodeling, alters hematopoietic stem cell functions, contributes to the commitment of mesenchymal stem cells, provides effects to immune homeostasis and defense against infections, and participates in energy metabolism and inflammation. BMAT has emerged as a significant contributor to the development and progression of various diseases, shedding light on its complex relationship with health. Notably, BMAT has been implicated in metabolic disorders, hematological malignancies, and skeletal conditions. BMAT has been shown to support the proliferation of tumor cells in acute myeloid leukemia and niche adipocytes have been found to protect cancer cells against chemotherapy, contributing to treatment resistance. Moreover, BMAT's impact on bone density and remodeling can lead to conditions like osteoporosis, where high levels of BMAT are inversely correlated with bone mineral density, increasing the risk of fractures. BMAT has also been associated with diabetes, obesity, and anorexia nervosa, with varying effects on individuals depending on their weight and health status. Understanding the interaction between adipocytes and different diseases may lead to new therapeutic strategies

Valproic acid for the treatment of low-risk myelodisplastic syndromes: a case report and a review of literature

none4openAntonella poloni; Benedetta Costantini; Marianna Mariani; Pietro LeoniPoloni, Antonella; Benedetta, Costantini; Marianna, Mariani; Leoni, Pietr

Human mesenchymal stem cells from chorionic villi and amniotic fluid are not susceptible to transformation after extensive in vitro expansion.

Mesenchymal stem cells (MSCs) are promising candidates for cell therapy and tissue engineering. Increasing evidence suggests that MSCs isolated from fetal tissues are more plastic and grow faster than adult MSCs. In this study, we characterized human mesenchymal progenitor cells from chorionic villi (CV) and amniotic fluid (AF) isolated during the first and second trimesters, respectively, and compared them with adult bone marrow-derived MSCs (BM). We evaluated 10 CV, 10 AF, and 6 BM samples expanded until the MSCs reached senescence. We used discarded cells from prenatal analyses for all the experiments. To evaluate the replicative stability of these cells, we studied the telomerase activity, hTERT gene transcription, and telomere length in these cells. Spontaneous chromosomal alterations were excluded by cytogenetic analysis. We studied the expression of c-myc and p53, tumor-associated genes, at different passage in culture and the capacity of these cells to grow in an anchorage-independent manner by using soft agar assay. We isolated homogeneous populations of spindle-shaped CV, AF, and BM cells expressing mesenchymal immunophenotypic markers throughout the period of expansion. CV cells achieved 14 ± 0.9 logs of expansion in 118 days and AF cells achieved 21 ± 0.9 logs in 118 days, while BM cells achieved 11 × 0.4 logs in 84 days. Despite their high proliferation capacity, fetal MSCs showed no telomerase activity, no hTERT and c-myc transcriptions, and maintained long, stable telomeres. A constant expression level of p53 and a normal karyotype were preserved throughout long-term expansion, suggesting the safety of fetal MSCs. In conclusion, our results indicate that fetal MSCs could be an alternative, more accessible resource for cell therapy and regenerative medicine

Molecular and functional characterization of human bone marrow adipocytes

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Post-transplant events Combined administration of alpha-erythropoietin and filgrastim can improve the outcome and cost balance of autologous stem cell transplantation in patients with lymphoproliferative disorders

autologous transplantation; erythropoietin; engraftment kinetic

Early lenalidomide treatment for low and intermediate-1 International Prognostic Scoring System risk myelodysplastic syndromes with del(5q) before transfusion dependence

Lenalidomide is approved for the treatment of transfusion-dependent (TD) del(5q) myelodysplastic syndromes (MDS). However, few data are available in patients with transfusion-independent (TI) del(5q) MDS. In the first, observational, part of this 2-part study, we assessed the impact of transfusion dependence on overall survival (OS) and non-leukemic death in untreated del(5q) MDS patients who were TD (n = 136),TI with hemoglobin (Hb) >= 10 mg/dL (n = 88),or TI with Hb = 10 g/dL],108 months;TI [Hb <10 g/dL],77 months;TD, 44 months). Transfusion dependence also negatively impacted non-leukemic death rates. In the interventional part of the study, baseline Hb levels were found to correlate significantly with physical (R = 0.666, P = 0.035) and fatigue (R = 0.604, P = 0.049) QoL scores. Median physical QoL scores improved significantly after 12 weeks' treatment with lenalidomide (+12.5;P = 0.020). Evaluable TI patients experienced early increases in Hb levels, and all attained an erythroid response. Our findings suggest that TI patients with moderate anemia may benefit from early treatment with lenalidomide

Evans syndrome: Disease awareness and clinical management in a nation‐wide ITP‐NET survey

Evans syndrome (ES) is rare and mostly treated on a "case-by-case" basis and no guidelines are available. With the aim of assessing disease awareness and current management of adult ES, a structured survey was administered to 64 clinicians from 50 Italian participating centers. Clinicians had to be involved in the management of autoimmune cytopenias and were enrolled into the ITP-NET initiative. The survey included domains on epidemiology, diagnosis, and therapy of ES and was designed to capture current practice and suggested work-up and management. Thirty clinicians who had followed a median of 5 patients (1-45)/15 years responded. The combination of AIHA plus ITP was more common than the ITP/AIHA with neutropenia (p &lt; .001) and 25% of patients had an associated condition, including lymphoproliferative syndromes, autoimmune diseases, or primary immunodeficiencies. The agreement of clinicians for each diagnostic test is depicted (i.e., 100% for blood count and DAT; only 40% for anti-platelets and anti-neutrophils; 77% for bone marrow evaluation). Most clinicians reported that ES requires a specific approach compared to isolated autoimmune cytopenias, due to either a more complex pathogenesis and a higher risk of relapse and thrombotic and infectious complications. The heterogeneity of treatment choices among different physicians suggests the need for broader harmonization