Anti-Human CD117 Antibodies Mediate Clearance of Myelodysplastic Syndrome Hematopoietic Stem Cells and Facilitate Establishment of Normal Hematopoiesis in Transplantation

Myelodysplastic syndrome (MDS) is an aging-associated group of clonal disorders characterized by ineffective hematopoiesis, leading to cytopenias and an increased risk of developing acute myeloid leukemia (AML). MDS arises from abnormal hematopoietic stem cells (HSCs). The only potentially curative therapy available for MDS patients is hematopoietic cell transplantation (HCT), but relapse is common, likely due to the inability of current therapies to effectively eliminate disease-initiating MDS HSCs.
Source: Biology of Blood and Marrow Transplantation - Category: Hematology Authors: Source Type: research

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Allogeneic stem cell transplantation (alloSCT) is a potentially curative therapeutic option for patients with myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML). Disease relapse occurs in 35-45% of patients following alloSCT, and is the most frequent cause of treatment failure and mortality [1-4]. Moreover, relapse after alloSCT is associated with poor prognosis despite salvage chemotherapy, donor lymphocyte infusions, and/or second transplants [4].
Source: Biology of Blood and Marrow Transplantation - Category: Hematology Authors: Source Type: research
Myelodysplastic syndromes (MDS) are clonal disorders of hematopoietic stem cells that mainly affect the elderly, characterized by ineffective hematopoiesis, leading to cytopenia, infections, and a significant reduction in the quality of life [1,2]. Intensive chemotherapy combined with hematopoietic stem cell transplantation (HSCT) is the only curative treatment for this disease. However, it's applicability in elderly patients is limited by comorbidities and poor performance status. Azacytidine (AZA) significantly reduces transfusion dependence, decreases the risk of transformation to acute myeloid leukemia (AML), and impro...
Source: Experimental Hematology - Category: Hematology Authors: Tags: Brief Communication Source Type: research
We report here indiscriminate killing of CD123+ normal and acute myeloid leukemia / myelodysplastic syndrome cells by SL-401, a diphtheria toxin interleukin-3 fusion protein. SL-401 induced cytotoxicity of CD123+ primary cells/blasts from acute myeloid leukemia and myelodysplastic syndrome patients but not CD123- lymphoid cells. Importantly, SL-401 was highly active even in cells expressing low levels of CD123, with minimal effect on modulation of the CD123 target in acute myeloid leukemia. SL-401 significantly prolonged survival of leukemic mice in acute myeloid leukemia patient-derived xenograft mouse models. In addition...
Source: Haematologica - Category: Hematology Authors: Tags: Haematologica Source Type: research
In patients with myeloid malignancies, such as acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS), relapse remains the main cause of treatment failure after allogeneic hematopoietic stem cell transplantation (allo-HSCT) [1-4]. Several studies addressing therapeutic strategies for relapse after allo-HSCT have shown that treatment is more effective when initiated at molecular relapse rather than at hematologic relapse [5]. Therefore, early detection of imminent relapse, ideally at a molecular level, is a prerequisite for successful therapeutic intervention and can be achieved by regular monitoring of minimal...
Source: Biology of Blood and Marrow Transplantation - Category: Hematology Authors: Source Type: research
This multicenter study evaluated a treosulfan-based regimen in children and young adults with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) undergoing allogeneic hematopoietic cell transplant (HCT). Forty patients with median age 11 years (1-19) underwent allogeneic HCT for AML in first (n=18), second (n=11), third or greater remission (n=3); or MDS (n=8) using bone marrow (n=25), peripheral blood stem cells (n=5) or cord blood (n=9). The regimen consisted of body surface area (BSA)-based treosulfan 10 g/m2/day (BSA ≤ 0.5 m2), 12 g/m2/day (BSA> 0.5 – 1.0 m2), or 14 g/m2/day (BSA> 1.0 m2) on ...
Source: Biology of Blood and Marrow Transplantation - Category: Hematology Authors: Source Type: research
Hematologic malignancies are more prevalent in older patients, and because of the increased rate of elderly in the population, the number of patients presenting with hematologic malignancy has increased [1]. The median ages of patients with acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS), which are the most common indication for allogeneic hematopoietic transplantation (alloHCT), in this population are 69 and 76 years, respectively [2-4]. Despite the advent of the novel agents, alloHCT remains the only curative option for most of the common hematologic malignancies.
Source: Biology of Blood and Marrow Transplantation - Category: Hematology Authors: Source Type: research
This multicenter study evaluated a treosulfan-based regimen in children and young adults with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) undergoing allogeneic hematopoietic cell transplant (HCT). Forty patients with median age 11 years (range, 1 to 19) underwent allogeneic HCT for AML in first (n  = 18), second (n = 11), and third or greater remission (n = 3) or MDS (n = 8) using bone marrow (n = 25), peripheral blood stem cells (n = 5), or cord blood (n = 9). The regimen consisted of body surface area (BSA...
Source: Biology of Blood and Marrow Transplantation - Category: Hematology Authors: Source Type: research
AbstractPrimary graft failure can be a cause of early morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT), as it leads to a high risk of severe infections and bleeding. Splenomegaly is associated with primary graft failure in patients of myelofibrosis, but the association between splenomegaly and outcomes after HSCT in patients with myeloid malignancies has not been previously evaluated. The aim of this study was to investigate the effect of spleen volume on engraftment kinetics in patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). We enrolled 85 patients. The...
Source: Annals of Hematology - Category: Hematology Source Type: research
A 62-year-old man with acute myeloid leukemia, evolved from myelodysplastic syndrome after allogeneic bone marrow transplant, was admitted to the hospital because of worsening fatigue and altered level of consciousness. On arrival at the hospital, the patient was markedly fatigued and had signs of encephalopathy. He reported no fevers, chills, or diaphoresis but noted new urinary incontinence and nausea. His medical history was notable for a matched unrelated donor allogeneic hematopoietic stem cell transplant (HCT), performed 35 days previously, as well as hypertension and peripheral vascular disease.
Source: Mayo Clinic Proceedings - Category: Internal Medicine Authors: Tags: Residents' Clinic Source Type: research
Pediatric myelodysplastic syndromes (MDSs) are a heterogeneous group of clonal disorders with an annual incidence of 1 to 4 cases per million, accounting for less than 5% of childhood hematologic malignancies. MDSs in children often occur in the context of inherited bone marrow failure syndromes, which represent a peculiarity of myelodysplasia diagnosed in pediatric patients. Moreover, germ line syndromes predisposing individuals to develop MDS or acute myeloid leukemia have recently been identified, such as those caused by mutations in GATA2, ETV6, SRP72, and SAMD9/SAMD9-L. Refractory cytopenia of childhood (RCC) is the m...
Source: Blood - Category: Hematology Authors: Tags: Pediatric Hematology, Transplantation, How I Treat, Free Research Articles, Myeloid Neoplasia Source Type: research
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