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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Conclusions: The low to medium doses of ATG may be associated with improving survival outcomes and reducing incidence of ecGVHD without enhancing the chances of relapse in patients with acute leukemia or myelodysplastic syndrome undergoing non-TBI-based HLA-mismatched allogeneic HSCT. PMID: 30616303 [PubMed - as supplied by publisher]
Source: The Korean Journal of Internal Medicine - Category: Internal Medicine Authors: Tags: Korean J Intern Med Source Type: research
The search for the optimal conditioning regimen prior to allogeneic hematopoietic stem cell transplant (HCT) for acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) has been ongoing for decades.[1, 2] Early conditioning regimens consisted of high-dose chemotherapy and radiation, now characterized as myeloablative conditioning (MAC), to achieve the aspired outcome of eliminating malignant disease with concomitant restoration of normal hematopoiesis. With experience and improved understanding of the graft-versus-leukemia effect, investigators began to lower the intensity of conditioning regimens.
Source: Biology of Blood and Marrow Transplantation - Category: Hematology Authors: Source Type: research
Immunotherapy has revolutionized therapy in both solid and liquid malignancies. The ability to cure acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) with an allogeneic hematopoietic stem cell transplant (HSCT) is proof of concept for the application of immunotherapy in AML and MDS. However, outside of HSCT, only the anti-CD33 antibody drug conjugate gemtuzumab ozogamicin is currently approved as an antibody-targeted therapy for AML. Several avenues of immunotherapeutic drugs are currently in different stages of clinical development.
Source: Blood Reviews - Category: Hematology Authors: Tags: Review Source Type: research
This study may open up new potential therapeutic avenues for the treatment of patients with chronic infection, inflammatory diseases, and cancer.DisclosuresNo relevant conflicts of interest to declare.
Source: Blood - Category: Hematology Authors: Tags: 506. Hematopoiesis and Stem Cells: Microenvironment, Cell Adhesion, and Stromal Stem Cells Source Type: research
BACKGROUND: Recipients of allogeneic HSCT experience significant short- and long-term healthcare burdens with differing general patterns of late effects between graft sources. For example, recipients of peripheral blood stem cell (PBSC) grafts benefit from more rapid engraftment after transplant as compared to bone marrow (BM) or umbilical cord blood (UCB), but experience a greater risk of chronic graft-versus-host disease (cGVHD) at later time points after HSCT. Little data exist regarding healthcare burden beyond first year of allogeneic HSCT, limiting our understanding of the long-term impact for each graft source.METHO...
Source: Blood - Category: Hematology Authors: Tags: 904. Outcomes Research-Malignant Conditions: Outcomes in Myeloid Malignancies and Allogeneic Stem Cell Transplant Source Type: research
Conclusion: OS was nearly threefold higher in the pooled cohort than in patients not receiving ATIR101 after haplo-HSCT in the historic control group. These outcomes were achieved without the need for concomitant high-dose immunosuppressive therapy. Disease relapse was limited and NRM in the pooled cohort was half that of the historic control group. Administration of a single dose of ATIR101 after a T-cell-depleted haplo-HSCT was well tolerated. The rate of GVHD is lower in the pooled cohort than the historic control group, suggesting that ATIR101 does not increase GVHD beyond the levels reported with a T-cell-depleted CD3...
Source: Blood - Category: Hematology Authors: Tags: 711. Cell Collection and Processing I Source Type: research
ConclusionOur first-in-human clinical trial demonstrates promising efficacy of cCAR therapy in treating patients with relapsed/ refractory AML. cCAR is able to eradicate leukemia blasts and leukemia stem cells, exerting a profound tumor killing effect that is superior to single target CAR T cell therapies. cCAR is also shown to induce total myeloid ablation in bone marrow, suggesting that it may act as a safer alternative to avoid the severe toxicities caused by standard bone marrow ablation regimens without sacrificing the anti-tumor efficacy. This strategy will likely benefit patients who are unable to tolerate total bod...
Source: Blood - Category: Hematology Authors: Tags: 616. Acute Myeloid Leukemia: Novel Therapy, excluding Transplantation: Immunotherapy Source Type: research
Conclusions:We have demonstrated the feasibility and safety of multiple injections of CYAD-01 without preconditioning chemotherapy. We evidenced promising anti-leukemic activity with 42% ORR in r/r AML with 5/7 pts having clinical benefit. Rates of G3/4 CRS were low and manageable. Updated safety, activity and correlative science data of the complete dose-escalation segment will be presented.DisclosuresSallman: Celgene: Research Funding, Speakers Bureau. Kerre: Celyad: Consultancy; BMS: Consultancy; Celgene: Consultancy, Research Funding. Davila: Celyad: Consultancy, Membership on an entity's Board of Directors or advisory...
Source: Blood - Category: Hematology Authors: Tags: 616. Acute Myeloid Leukemia: Novel Therapy, excluding Transplantation: Immunotherapy Source Type: research
Dyskeratosis congenita (DC) belongs to the group of inherited bone marrow failure syndromes (IBMFS) and is characterized by premature telomere shortening caused by mutations in components of the telomerase or the shelterin complexes. The main cause of death in affected patients is hematopoietic failure, but there is also a 10-15% risk of malignant transformation into secondary myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Critically short telomeres activate a DNA damage response with p53-mediated cell cycle inhibition, senescence and/or apoptosis, the latter mediated primarily by PUMA, a BCL-2 family mem...
Source: Blood - Category: Hematology Authors: Tags: 508. Bone Marrow Failure: Inherited Bone Marrow Failure: Germline Genetic Disorders Source Type: research
We report on updated feasibility and efficacy data.Methods: Pts aged 18-65 yrs with newly diagnosed AML (≥20% blasts by WHO criteria) and high risk MDS (≥10% blasts) were eligible if they had adequate performance status (ECOG ≤2) and organ function. Treatment included 1-2 induction cycles of (A) 1.5 g/m2 over 24 hours (days 1-4) and (I) 12 mg/m2 (days 1-3). Nivo 3 mg/kg was started on day 24±2 and continued every 2 weeks for up to a yr. For pts achieving complete response (CR) or CR with incomplete count recovery (CRi), up to 5 consolidation cycles of attenuated dose I+A was given. Eligible pts received all...
Source: Blood - Category: Hematology Authors: Tags: 616. Acute Myeloid Leukemia: Novel Therapy, excluding Transplantation: Immunotherapy Source Type: research
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