Allogeneic hematopoietic stem cell transplantation (alloHSCT) is a potentially curative treatment for acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). However, these transplants are complicated by a high rate of relapse in very high cytogenetic risk or refractory diseases. The benefit of this therapeutic strategy for these serious malignant hemopathies could therefore be reassessed.
View Article and Find Full Text PDFBackground: Failure of gastrointestinal acute graft--host disease (GI-aGvHD) to respond to steroid therapy is associated with limited further therapeutic options. We aimed to assess the safety and efficacy of the first-in-human use of the pooled allogeneic faecal microbiota, MaaT013, for the treatment of steroid-refractory GI-aGvHD.
Methods: This prospective, international, single-arm, phase 2a study reports clinical outcomes from a 24-patient cohort with grade III-IV, steroid refractory GI-aGvHD treated with the pooled allogeneic faecal microbiota MaaT013.
Limosilactobacillus fermentum CECT5716, a probiotic strain isolated from human milk, has reported beneficial effects on different gastrointestinal disorders. Moreover, it has shown its ability to restore altered immune responses, in association with microbiome modulation in different pathological conditions. Therefore, our aim was to assess the effects of a Limosilacbacillus fermentum CECT5716 in a rat experimental model of irritable bowel syndrome (IBS) that resembles human IBS.
View Article and Find Full Text PDFBackground: Post-transplant cyclophosphamide (PT-Cy) has become a standard of care in haploidentical hematopoietic stem cell transplantation (HSCT) to reduce the risk of graft-versus-host disease. However, data on cardiac events associated with PT-Cy are scarce.
Objectives: This study sought to assess the incidence and clinical features of cardiac events associated with PT-Cy.
Patients receiving allogeneic hematopoietic cell transplantation (alloHCT) were previously shown to display a bacterial gut dysbiosis; however, limited data are available regarding the role of fungal microbiota in these patients. We evaluated the bacterial and fungal composition of the fecal microbiota at day 0 of alloHCT. Higher bacterial diversity was associated with an improved overall survival (OS) and disease-free survival (DFS).
View Article and Find Full Text PDFIntroduction: The orexinergic system is one of the chemical mediators that modulate the gut-brain axis, given the involvement of hypothalamic orexin A (OXA) in gastrointestinal motility and secretion, and the presence of OXA in enteroendocrine cells of the intestinal mucosa and in primary afferent neurons of the mesenteric plexus, permitting its participation in gut-brain signaling.
Aim: The source of OXA and the signal(s) triggering its peripheral release are not fully understood, and it is not known whether it acts on orexigenic receptors in peripheral tissues to meet physiological or pathological demands. The aim of this review is to address these questions in the light of new data indicating that OXA may have functions in the gut-brain axis that go beyond its participation in energy homeostasis.
It is increasingly evident that bidirectional gut-brain signaling provides a communication pathway that uses neural, hormonal, and immunological routes to regulate homeostatic mechanisms such as hunger/satiety as well as emotions and inflammation. Hence, disruption of the gut-brain axis can cause numerous pathophysiologies, including obesity and intestinal inflammatory diseases. One chemical mediator in the gut-brain axis is orexin-A, given that hypothalamic orexin-A affects gastrointestinal motility and secretion, and peripheral orexin in the intestinal mucosa can modulate brain functions, making possible an orexinergic gut-brain network.
View Article and Find Full Text PDFWe assessed the outcomes associated with thiotepa, busulfan and fludarabine (TBF) conditioning regimen in a cohort of 29 consecutive patients allografted for myelofibrosis (MF). The median age was 56 (range 42-70) years. According to the refined Dynamic International Prognostic Scoring System (DIPSS-plus), 15 (52%) patients were classified as high risk.
View Article and Find Full Text PDFBackground Aims: Corticosteroids are the standard first-line treatment for acute graft-versus-host disease (aGVHD), but they are associated with many complications, and less than half of patients have a sustained response.
Methods: To improve outcomes, we performed a retrospective study to analyze the efficacy of the addition of extracorporeal photopheresis (ECP) to low-dose corticosteroids in 37 adult patients (median age, 57 years) with skin-predominant aGVHD (grade I, n = 17; grade II, n = 18; and grade III, n = 2). All patients received ECP in combination with 1 mg/kg prednisone (n = 26) or topical steroids (n = 11).
Introduction/background: Azacytidine (AZA) has been used as a promising treatment for relapse after allogeneic transplantation. A clear benefit has been demonstrated when treating patients with a reduced disease burden, thus a prophylactic and preemptive approach to these patients has emerged.
Materials And Methods: We retrospectively analyzed patients with myeloid malignancies treated with azacytidine in the posttransplantation setting between September 2013 and April 2018 in a single tertiary care hospital.
We report results of a thiotepa-based conditioning in haploidentical stem cell transplantation (haplo-SCT) with posttransplant cyclophosphamide (PT-CY) and antithymocyte globulin (ATG), for unmanipulated peripheral blood stem cell (PBSC) transplants, in 80 patients with hematological malignancies. Patients in complete remission (CR) received a thiotepa-busulfan-fludarabine (TBF) regimen, while patients with relapsed/refractory (R/R) malignancies received a sequential regimen consisting of thiotepa-etoposide-cyclophosphamide (TEC) and reduced-intensity conditioning (RIC). The median age was 52 (range, 17-72) years, 44% patients had R/R disease at transplant, and the median follow-up was 417 (range, 180-1595) days.
View Article and Find Full Text PDFObjectives: This retrospective study analyzed the impact of early cyclosporine A (CsA) initiation (day -3) on the risk of acute graft-vs-host disease (aGvHD) after haploidentical hematopoietic cell transplantation (Haplo-HCT) using post-transplant cyclophosphamide.
Methods: Sixty-one consecutives patients who underwent Haplo-HCT were analyzed.
Results: At day +180, the cumulative incidences of grade II-IV and grade III-IV aGvHD were 39% and 18%, respectively.
We report the outcomes of 51 patients who underwent unmanipulated haploidentical hematopoietic stem cell transplantation (haplo-HSCT) with post-transplantation cyclophosphamide (PT-Cy) and antithymocyte globulin (ATG), from peripheral blood stem cells (PBSCs) or bone marrow, after receipt of a TBF (thiotepa, busulfan, and fludarabine) conditioning regimen. Their median age was 55 years (range, 16 to 72 years). Hematologic diagnoses included acute leukemias (n = 31), lymphoid neoplasm (n = 12), myeloproliferative neoplasm (n = 5), and myelodysplastic syndromes (n = 3).
View Article and Find Full Text PDFMultiple myeloma (MM) results from expansion of abnormal plasma cells in the bone marrow (BM). Previous studies have shown that monocytes play a crucial role in MM pathophysiology. A 6-sulfo LacNAc-expressing population of dendritic cells (Slan-DCs) that overlaps with intermediate and non-classical monocytes in terms of phenotype has been described.
View Article and Find Full Text PDFIn industrialized societies, food intake is largely determined by its hedonic characteristics, which can be modified by our experience via taste learning. In this learning, the hedonic value of a neutral flavor changes after its association with a motivationally significant stimulus. Experiment 1 analyzes the effect of orexin administration (53 and 107 ng) in the ventral tegmental area (VTA) on hedonic intake through acquisition of a flavor-taste preference and a flavor-taste aversion.
View Article and Find Full Text PDFCytomegalovirus is one of the main contributing factors to high mortality rates in patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT). The main factors of treatment failure are both drug resistance and intolerance. In some cases, Cytotect®CP CMV-hyperimmune globulin is used as salvage therapy.
View Article and Find Full Text PDFSinusoidal obstruction syndrome (SOS), also known as hepatic veno-occlusive disease (VOD), is a serious complication after hematopoietic stem cell transplantation (HSCT). SOS/VOD usually occurs within 3 weeks of HSCT, but the 2016 European Society for Blood and Marrow Transplantation diagnosis criteria have been revised to include late forms. Prophylactic use of defibrotide is recommended in the pediatric setting, but its value remains uncertain in the adult population.
View Article and Find Full Text PDFThe treatment of older patients with acute myeloid leukemia that is secondary to previous myelodysplastic syndrome, myeloproliferative neoplasm, or prior cytotoxic exposure remains unsatisfactory. We compared 92 and 107 patients treated, respectively, with intensive chemotherapy or azacitidine within two centres. Diagnoses were 37.
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