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Toll like receptor 2 (TLR2) signaling promotes apoptosis of premalignant hematopoietic stem and progenitor cells in a mouse model of myelodysplastic syndrome

The myelodysplastic syndromes (MDS) are hematopoietic stem cell (HSC) disorders characterized by ineffective hematopoiesis and a high risk of leukemic transformation. The only curative treatment is stem cell transplantation; thus new therapies are needed. Multiple studies have shown a correlation between MDS and enhanced toll like receptor 2 (TLR2) signaling, suggesting this might contribute to disease pathogenesis. In fact, an inhibitory TLR2 antibody is currently in clinical trial for use in MDS (OPN-305, Opsona Therapeutics).
Source: Experimental Hematology - Category: Hematology Authors: Source Type: research

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Allogeneic stem cell transplant (ASCT) with HLA matched donors is increasingly used for older patients with AML/MDS. It remains unclear if haploidentical transplantation (haploSCT) is a suitable option for older patients with this disease. We analyzed 43 patients with AML/MDS (median age 61 years) who underwent a haploSCT at our institution. All the patients received a fludarabine-melphalan-based reduced-intensity conditioning regimen and post-transplant cyclophosphamide-based GVHD prophylaxis. Except one patient who had early death, the remaining 42 patients (98%) engrafted donor cells.
Source: Biology of Blood and Marrow Transplantation - Category: Hematology Authors: Source Type: research
Bone Marrow Transplantation, Published online: 11 September 2017; doi:10.1038/bmt.2017.171
Source: Bone Marrow Transplantation - Category: Hematology Authors: Source Type: research
Validation of the revised IPSS at transplant in patients with myelodysplastic syndrome/transformed acute myelogenous leukemia receiving allogeneic stem cell transplantation: a retrospective analysis of the EBMT chronic malignancies working party Bone Marrow Transplantation advance online publication, September 11 2017. doi:10.1038/bmt.2017.171 Authors: C Scheid, L de Wreede, A van Biezen, C Koenecke, G Göhring, L Volin, J Maertens, J Finke, J Passweg, D Beelen, J J Cornelissen, M Itälä-Remes, P Chevallier, N Russell, E Petersen, N Milpied, C Richard Espiga, A Peniket, J Sierra, G Mufti, C Crawley, J H Ve...
Source: Bone Marrow Transplantation - Category: Hematology Authors: Source Type: research
Rationale: Myeloid sarcoma (MS) and leukemia cutis (LC) are extramedullary tumors comprising myeloid blasts. They can occur de novo or concurrently with hematological disorders, usually acute myeloid leukemia (AML). AML chemotherapy is generally the initial therapy for MS and LC, and hematopoietic stem cell transplantation (HSCT) can be considered as additional therapy. However, treatment for older patients who are unable to continue intensive chemotherapy is not currently standardized. Patient concerns: A 71-year-old Japanese woman was diagnosed with multiple MSs associated with myelodysplastic syndrome (MDS), using bone...
Source: Medicine - Category: Internal Medicine Tags: Research Article: Clinical Case Report Source Type: research
Allogeneic hematopoietic stem cell transplantation (AHSCT) is a successful treatment modality for AML and MDS. Information on transplant outcomes among older patients is limited because of concern of adverse transplant-related mortality (TRM) and poor overall survival (OS).
Source: Clinical Lymphoma, Myeloma and Leukemia - Category: Hematology Authors: Source Type: research
Allogeneic transplantation is the only curative therapy for the Myelodysplastic Syndromes (MDS). Older prognostic systems such as the IPSS and IPSS-R can help determine the appropriateness of allogeneic stem cell transplantation (SCT), however the incorporation of molecular genetic profiling in MDS can allow us to refine our decision making process – not only to help decide who should undergo SCT, but how they should undergo SCT.
Source: Clinical Lymphoma, Myeloma and Leukemia - Category: Hematology Authors: Source Type: research
Hematopoietic stem cell transplantation (HSCT) is considered the gold standard for treatment of hematologic malignancies, including Fanconi anemia (FA), a cancer-prone disease with extremely high incidence of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). However, eradication of residual leukemia stem cells (LSCs), which often contributes to relapse, remains the challenge for HSCT. Here we investigate the interaction between leukemic mesenchymal niche and donor hematopoietic stem progenitor cells (HSPCs) by modeling FA HSCT.
Source: Experimental Hematology - Category: Hematology Authors: Source Type: research
The number of allogeneic hematopoietic stem cell transplantations (allo-HCTs) performed each year with curative intent for older adults with acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS) has continued to rise over the past decade. Much of the progress in the use of allo-HCT in older adults is due to the use of reduced-intensity conditioning (RIC) regimens, which have allowed many older patients with AML or MDS to receive curative allo-HCT [1]. Without RIC, these older patients would otherwise be unfit for allo-HCT because of the toxicity associated with myeloablative conditioning regimens.
Source: Biology of Blood and Marrow Transplantation - Category: Hematology Authors: Source Type: research
AbstractAcute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) are clinically and molecularly heterogeneous clonal myeloid disorders with a poor prognosis especially in the relapsed refractory setting and in patients above the age of 60. While allogeneic hematopoietic stem cell transplantation (ASCT) is a potentially curative approach, high relapse, morbidity, and mortality rates necessitate the development of alternative therapies. Immune checkpoint inhibitors unmask tumoral immune tolerance and have demonstrated efficacy in the treatment of chemotherapy-resistant hematologic and solid malignancies. The rationale...
Source: Annals of Hematology - Category: Hematology Source Type: research
AbstractAllogeneic hematopoietic stem cell transplantation (allo-HSCT) is the ideal treatment for several diseases. However, the morbidity and mortality associated with the procedure might limit its widespread use; therefore, we implemented reduced BUCY2 as conditioning method along with the use of G-CSF-primed bone marrow (G-BM) in order to reduce complications, including graft-versus-host-disease (GVHD), and to improve survival in these patients. An analysis of transplant characteristics, complications, and survival of patients undergoing an allo-HSCT using this conditioning regimen (busulfan 12  mg/kg and cyclophos...
Source: Annals of Hematology - Category: Hematology Source Type: research
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