Chidamide shows synergistic cytotoxicity with cytarabine via inducing G0/G1 arrest and apoptosis in myelodysplastic syndromes.

In this study, the combination of chidamide (50 nM) with cytarabine (50 nM) showed synergistic inhibition on cell growth.The mean combination index values were 0.068, 0.158, and 0.226 in SKM-1, MUTZ-1, and KG-1 MDS cell lines, respectively. The combination increased the acetylation levels of histone H3 and decreased HDAC activity in MDS cells.A low concentration (25 and 50 nM) of chidamide combined with low-dose cytarabine (50 nM) inhibited cell proliferation and arrested the cell cycle in the G0/G1 phasevia down-regulating CDK2 and up-regulating p21. Furthermore, the combined treatment induced cell apoptosis via down-regulating Bcl-2 and up-regulating cleaved caspase-3 protein. These results demonstrate the potential utility of combining chidamide and cytarabine in the treatment of MDS. PMID: 29312515 [PubMed]
Source: American Journal of Translational Research - Category: Research Tags: Am J Transl Res Source Type: research

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Acute myeloid leukemia (AML) treatment options for older patients with AML either for first line or in relapsed/refractory cases are limited, with very poor outcomes (1 –3). Elderly patients are often ineligible for intensive anti-leukemic chemotherapy (CHT) or participation to clinical trial due to poor performance status and/or organ dysfunction. This population has an increased incidence of pre-existing myelodysplastic syndrome (MDS), unfavorable cytogenetics and multi-drug-resistant phenotype, any of which can impair the efficacy of intensive antileukemic CHT (1–3).
Source: Leukemia Research - Category: Hematology Authors: Tags: Research paper Source Type: research
Introduction: Real-world survival for pts with MDS treated with HMAs is substantially inferior than the landmark AZA-001 trial (median OS, 11-16 and 24.5 months, respectively). The reasons behind this gap remain unclear. Clinical use of HMAs differs from traditional chemotherapy in that multiple HMA cycles are generally required before responses are observed, therapy is continued even in the presence of significant cytopenias, and therapy must be continued to sustain response. We hypothesized that practice at academic hospital setting or prior experience of providers in treating MDS pts (more specifically the number of pts...
Source: Blood - Category: Hematology Authors: Tags: 904. Outcomes Research-Malignant Conditions: Outcomes in Myeloid Malignancies and Allogeneic Stem Cell Transplant Source Type: research
Conclusions:In population-based analyses, the survival of t-MDS remains dismal with outcomes particularly worse with advancing age and following primary cancer sites that are typically managed with combined modality regimens including chemotherapy and radiation. Findings from the real-world population level data such as this should be used as outcome benchmarks in clinical trials to assess therapeutic effectiveness of experimental treatments.DisclosuresGerds: Apexx Oncology: Consultancy; Celgene: Consultancy; Incyte: Consultancy; CTI Biopharma: Consultancy. Nazha: MEI: Consultancy. Carraway: Jazz: Speakers Bureau; FibroGen...
Source: Blood - Category: Hematology Authors: Tags: 904. Outcomes Research-Malignant Conditions: Outcomes in Myeloid Malignancies and Allogeneic Stem Cell Transplant 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
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
ConclusionAt UCDCCC, VEN in combination with an HMA is well tolerated and produces high rates of response in adult patients with AML. Response rates for TN AML, sAML and multiple molecular subgroups are consistent with prior reports, while higher than expected response rates and survival were seen in R/R AML. Responses were also seen in post-MDS/MPN and post-MF patients. In extended follow-up, survival has been durable in patients with cCR, but not MLFS. The use of VEN plus HMA combinations in adults with AML represents a viable treatment option for both TN and R/R AML.DisclosuresJonas: AbbVie: Consultancy, Research Fundin...
Source: Blood - Category: Hematology Authors: Tags: 615. Acute Myeloid Leukemia: Commercially Available Therapy, excluding Transplantation: Poster I Source Type: research
Conclusions: In this subgroup analysis, CPX-351 improved OS and remission rates compared with 7+3 in older adults with AML-MRC, while maintaining a similar safety profile. Importantly, CPX-351 is the first agent to be associated with prolonged OS compared with standard-of-care chemotherapy (7+3 regimen) in adults with newly diagnosed AML-MRC, which supported FDA approval in this population.DisclosuresRyan: AbbVie: Equity Ownership; University of Rochester: Patents &Royalties. Uy: Curis: Consultancy; GlycoMimetics: Consultancy. Cortes: Astellas Pharma: Consultancy, Research Funding; Novartis: Consultancy, Research Fundi...
Source: Blood - Category: Hematology Authors: Tags: 615. Acute Myeloid Leukemia: Commercially Available Therapy, excluding Transplantation: Poster I Source Type: research
ConclusionsThe long-term overall survival of the patients treated on S0816 remains high (94%) at 5 years. Despite historical data suggesting favorable clinical outcomes in patients with a negative PET2, nearly 25% of these patients experienced relapse events, demonstrating limitations of a PET-adapted approach and of standard frontline therapy with ABVD. In patients who were PET2+, PFS was favorable relative to historical series, but was associated with a high rate of secondary malignancies. Our results emphasize the importance of long-term follow-up in this disease, and the need for better biomarkers at diagnosis of HL an...
Source: Blood - Category: Hematology Authors: Tags: 624. Hodgkin Lymphoma and T/NK Cell Lymphoma-Clinical Studies: Hodgkin Lymphoma: Chemotherapy and Response Adapted Approaches Source Type: research
Our group developed a 161533 trispecific killer engager (TriKE) molecule to target acute myeloid leukemia (AML) cells using Natural Killer (NK) cells. This molecule contains an anti-CD16 camelid nanobody to activate NK cells, an anti-CD33 single chain variable fragment (scFv) to engage cancer targets, and an IL-15 molecule that drives NK cell priming, expansion and survival. Using an earlier version of this molecule, we have shown that the CD33 TriKE is effective at activating NK cells against AML targets in vitro and in vivo. This preclinical data has lead to the establishment of a clinical trial in refractory AML patient...
Source: Blood - Category: Hematology Authors: Tags: 616. Acute Myeloid Leukemia: Novel Therapy, excluding Transplantation: Poster I Source Type: research
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