A Single Dose of a Novel Anti-Human Short Half-Life Engineered CD45-Targeted Antibody-Drug Conjugate (ADC) Is Cytoreductive on Patient-Derived Tumors and Extends Survival Beyond Standards of Care in Multiple Pre-Clinical Models of Hematologic Malignancy

For patients with refractory or high-risk hematologic malignancies, like acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), and acute lymphoblastic leukemia (ALL), allogeneic hematopoietic stem cell transplant (Allo-HSCT) is a potentially curative approach. Morbidities and mortality associated with current conditioning regimens limit the use of this curative procedure. As a result, many eligible patients do not consider transplant and 2/3 of those transplanted are only able to tolerate a reduced intensity conditioning regimen, which is associated with increased relapse rates (Scott, J Clin Onc 2017).
Source: Biology of Blood and Marrow Transplantation - Category: Hematology Authors: Tags: 128 Source Type: research

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Conclusions The discovery of JAK2V617F mutation in BCR-ABL1-negative MPNs by four different international cooperative groups in 2005 (2–5) led to significant insights on the pathogenesis of these disorders. In fact, this mutation results in a gain-of-function with activation of cytokine and growth factor receptors, and thus of the downstream JAK-STAT pathway (79, 95–98). The JAK2 point mutation in exon 12, present in a small percentage of patients with PV, is able to induce the MPN phenotype through the same pathogenic mechanism (6, 7). In 2006 the MPLW515L/K was reported in ET and PMF patients (44, 45) and d...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
This study proposed a pilot study of a new tool for a reliable and accurate stratification of patients with acute leukemia based on an integrative model of leukemia behavior, cell characterization, and clinical features, in addition, to an evaluation of intra-tumor and inter-tumor heterogeneity. Together our approach allows us to introduce an integrative quantitative approach to use zebrafish and tumor characterization as a prediction tool for the behavior of acute leukemia in young adults. Materials and Methods Animal Care and Handling Zebrafish wild-type (A/B and TAB5) adults were raised and maintained according to st...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
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
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
CONCLUSIONSFLAG-IDA HCT is a feasible strategy for relapsed/refractory acute leukemia patients that would have otherwise an extremely dismal prognosis. Yet, this regimen is associated with high early non-relapse mortality. Modifications of this regimen are warranted in order to reduce non-relapse mortality, without compromising the anti-leukemic effect.DisclosuresNo relevant conflicts of interest to declare.
Source: Blood - Category: Hematology Authors: Tags: 732. Clinical Allogeneic Transplantation: Results Source Type: research
In this study, we looked at the presence of this CNVdup14 in a cohort of Caribbean islands patients (pts) with non-secondary aggressive hematological malignancies (HM). We also studied the expression of ATG2B and GSKIP genes in a cohort of acquired AML pts.This is a retrospective multicenter study of adults Caribbean islands pts treated at Gustave Roussy Cancer Center (Villejuif, France) and at the French West Indian hospitals (Martinique and Guadeloupe) between May 2000 and May 2018. We included pts with AML, acute undifferentiated leukemia (AUL), acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LL). Pts wit...
Source: Blood - Category: Hematology Authors: Tags: 617. Acute Myeloid Leukemia: Biology, Cytogenetics, and Molecular Markers in Diagnosis and Prognosis: Poster I Source Type: research
Post-transplant lymphoproliferative disorder (PTLD) following hematopoietic stem cell transplantation (HSCT) is a rare, but life-threatening complication. PTLD typically develops within 6-12 months of HSCT, which is before the reconstitution of EBV-specific cytotoxic T-cell immunity. Several risk factors for developing PTLD have been reported in the literature, including the use of antithymocyte globulin (ATG) and ex vivo T-cell depletion (TCD). However, only a few large-scale retrospective studies have been conducted and risk scores have not yet been well defined. Therefore, to further evaluate the probability of and risk...
Source: Blood - Category: Hematology Authors: Tags: 723. Clinical Allogeneic and Autologous Transplantation: Late Complications and Approaches to Disease Recurrence: HSCT Late Effects and Disease Monitoring Source Type: research
Introduction:Allogeneic hematopoietic cell transplantation (alloHCT) has historically been reserved for younger, fit patients with hematologic malignancies. With the introduction of non-myeloablative conditioning regimens and improved supportive care, alloHCT has been increasingly offered to older adults.Objectives:To determine the association between functional status as measured by a cancer-specific comprehensive geriatric assessment (CGA) and post-transplant outcomes in an older alloHCT patient population.Methods:We conducted a prospective cohort study of patients aged 50 or older who underwent alloHCT at the University...
Source: Blood - Category: Hematology Authors: Tags: 904. Outcomes Research-Malignant Conditions: Poster II Source Type: research
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