cytarabine

Treatment with various agents including decitabine, cytarabine, daunorubicin, etoposide, and venetoclax, and two experimental bromodomain and extraterminal (BET) inhibitors did not produce sustained remissions, and the patient eventually succumbed to her disease. T-cell phenotype is an exceedingly rare feature of AML ex CMML, and whether this unique differentiation pathway contributed to the aggressive disease course remains unclear. Trial Registration: ClinicalTrials.gov identifier: NCT02543879, NCT03360006.

Traditional AML treatments employ cytarabine and anthracyclines drugs...For example, the introduction of midostaurin, the first FLT3 inhibitor, improved patient outcomes...Future directions, including personalized therapies and novel drug designs, are examined to provide updated insights into FLT3-targeted treatments. This comprehensive review aims to guide clinicians and researchers in the development of innovative therapies to improve AML patient outcomes.

This case highlights the complexity of MDS and the importance of genetic abnormalities in treatment planning. Persistent MECOM rearrangement and the TNIP1::PDGFRB chimera emphasize the need for further research into resistance mechanisms.

P3, N=92, Active, not recruiting, National Cancer Institute (NCI) | N=302 --> 92 | Trial completion date: May 2025 --> Dec 2025 | Trial primary completion date: May 2025 --> Jun 2024

P2, N=78, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Sep 2024 --> Nov 2025

P1, N=61, Active, not recruiting, Nkarta, Inc. | Trial primary completion date: Jul 2024 --> Oct 2024

P3, N=359, Completed, Kite, A Gilead Company | Active, not recruiting --> Completed

Cytarabine, daunorubicin, and etoposide (ADE) have been the standard backbone of induction chemotherapy regimens for acute myeloid leukemia (AML) patients for over five decades. We identified seveal mediators that would represent clinically and biologically significant genes for ADE treatment, such as BCL2, CLIP2, and VAV3, which are resistant genes with high expression associated with poor outcomes in pAML treated with ADE, and GRPEL1, HCFC1, and TAF10, which are sensitive genes with high expression showing beneficial outcomes. Notably, knockdowns of the BCL2, CLIP2, and VAV3 genes sensitize the ADE component in AML cell lines, suggesting that these genes should be further studied as potential therapeutic targets to overcome chemoresistance.

P1/2, N=38, Terminated, Hoffmann-La Roche | Completed --> Terminated; Study was terminated by the sponsor based on insufficient tolerability and efficacy to proceed beyond Part 1b.

P2, N=60, Not yet recruiting, Institute of Hematology & Blood Diseases Hospital, China

P1, N=18, Active, not recruiting, Uma Borate | Recruiting --> Active, not recruiting | Trial completion date: Jan 2025 --> Dec 2025 | Trial primary completion date: Jan 2025 --> Jun 2025

P3, N=300, Not yet recruiting, Institute of Hematology & Blood Diseases Hospital, China

P=N/A, N=230, Not yet recruiting, Peking University People's Hospital

P1/2, N=122, Completed, BerGenBio ASA | Active, not recruiting --> Completed

P2, N=50, Recruiting, First Affiliated Hospital of Zhejiang University

P2, N=52, Recruiting, H. Lee Moffitt Cancer Center and Research Institute | Not yet recruiting --> Recruiting

189 AML patients receiving standard cytarabine and anthracycline-based induction treatment were included...Heightened inflammation and suboptimal nutritional status correlate with unfavourable prognoses in AML patients. Such insights hold the potential for guiding clinical decision-making, offering easily accessible prognostic information for the induction treatment of eligible AML patients.

P1, N=42, Recruiting, St. Jude Children's Research Hospital | Trial completion date: Jul 2025 --> Jun 2027

P3, N=727, Completed, ECOG-ACRIN Cancer Research Group | Active, not recruiting --> Completed

P3, N=123, Recruiting, BeiGene | Trial completion date: Mar 2025 --> Feb 2026 | Trial primary completion date: Sep 2024 --> Feb 2026

P2, N=20, Recruiting, Eastern Cooperative Oncology Group | Trial completion date: Oct 2024 --> Jun 2027 | Trial primary completion date: Oct 2024 --> Jun 2027

P1, N=19, Terminated, M.D. Anderson Cancer Center | Active, not recruiting --> Terminated; Administratively Complete

Patients who achieved CR or CRi received 3 courses of high-dose ARA-C (Cytarabine) 3000 mg/m2 every 12 h on days 1, 3, and 5, along with midostaurin at the dose of 50 mg b.i.d from Day 8 to Day 21 as part of consolidation therapy. The RI was 38.8% in the CBFB::MYH11 and 66.6% in the RUNX1::RUNX1T1 group. MRD (Measurable Residual Disease) was assessed by RQ-PCR at 10 time points throughout the study, as indicated by arrows.

P1/2, N=543, Active, not recruiting, Genmab | Recruiting --> Active, not recruiting

P2/3, N=745, Completed, Universitätsklinikum Hamburg-Eppendorf | Active, not recruiting --> Completed

P2, N=360, Active, not recruiting, ECOG-ACRIN Cancer Research Group | Trial completion date: Mar 2025 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025

To target this pathway, we investigated the activity of the potent chloroquine-derived autophagy inhibitor, Lys05, on human AML cells, patient samples, and patient derived xenograft models...Moreover, Lys05 overcame hypoxia-induced chemoresistance and improved the efficacy of cytarabine, venetoclax, and azacytidine in vitro and in vivo in AML models. Our results demonstrate the importance of autophagy, specifically mitophagy, as a critical survival and chemoresistance mechanism of AML cells under hypoxic marrow conditions. Therapeutic targeting of this pathway in future clinical studies for AML is warranted.

P2, N=141, Active, not recruiting, Fondazione Italiana Linfomi - ETS | Trial completion date: Jul 2025 --> Nov 2025

An Ara-C-containing intensified induction therapy followed by autologous stem cell transplantation (ASCT) is considered a highly effective treatment strategy in younger mantle cell lymphoma (MCL) patients, inducing long-lasting remissions...With the recently published results of the TRIANGLE trial, showing superiority of an ibrutinib-containing immunochemotherapy induction followed by ASCT compared with the standard therapy and, more strikingly, a noninferiority of an ibrutinib-containing regimen without ASCT compared with the standard regimen with ASCT, we consider the addition of ibrutinib to first-line therapy in younger MCL patients as a new standard of care...For patients with TP53 aberrations, ASCT should not be recommended due to potential toxicity and limited efficacy in this high-risk subgroup. Large randomized clinical trials such as ECOG-ACRIN 4151 will help to ultimately clarify the role of ASCT.

The ongoing development of molecularly targeted therapies in addition to the new standard of care combination of azacitidine and venetoclax (AZA-VEN) has transformed the prognostic outlook for older, transplant-ineligible patients with acute myeloid leukemia (AML). While conventional treatments, such as standard anthracycline and cytarabine- based chemotherapy or hypomethylating agent (HMA) monotherapy, are associated with a generally poor prognosis in this patient population, the use of these novel regimens can result in long-lasting, durable remissions in select patient subgroups...Additional studies defining the prognostic role of measurable residual disease following VEN-based treatment have further advanced prognostication capabilities and increased the ability for close disease monitoring and early targeted intervention prior to morphologic relapse. This review summarizes these recent developments and their impact on the treatment and survival of transplant-ineligible patients living with AML.

This study presents the important role of FLT3-ITD mutation via its downstream signaling (PI3K/AKT) in the outcome of D3A7 induction therapy. The FLT3-ITD mutation plays an important role in the 12-month survival of AML patients after D3A7 therapy. However, the outcome of D3A7 therapy and FLT3-ITD mutation were not associated with leukemia stem cells.

Remarkably, 5-azacytidine and cytarabine upregulated the expression of OTUD7B and exhibited a synergistic anti-lymphoma effect in PTCL. In summary, our study confirmed the prognostic role of OTUD7B in PTCL and the promising therapeutic potential of combining 5-azacytidine or cytarabine and doxorubicin for PTCL treatment.

For the in vitro study, an MTT assay was performed, and then different combinations against the THP-1 cell line were used as follows: non-treated cells, THP-1/ATOR IC50, THP-1/cytarabine (CYT) IC50, THP-1/doxorubicin (DOX) IC50, THP-1/DOX/CYT, THP-1/ATOR/CYT, THP-1/ATOR/DOX, and THP-1/ATOR/CYT/DOX...G4 was treated with Bevacizumab (Bev) (5 mg/kg)...Furthermore, in vivo co-treatment with ATOR/Bev decreased tumor incidence and size with a significant reduction of the immunohistochemical PCNA (LI%) in lung parenchyma, targeting PI3K/Akt/mTOR, and VEGF-A signaling pathways. Co-treatment with ATOR and chemotherapies led to cell cycle arrest, modulation of the PI3K/Akt/mTOR, and VEGF-A signaling pathways in tumor cells.

P2, N=65, Active, not recruiting, University of Southampton | Recruiting --> Active, not recruiting | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Oct 2024 --> May 2026

P3, N=700, Recruiting, Daiichi Sankyo | Not yet recruiting --> Recruiting

P3, N=488, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2024 --> Mar 2025

P1/2, N=20, Not yet recruiting, Stanford University | Initiation date: Oct 2024 --> Jan 2025

In summary, high HIF-1α expression is potentially a baseline prognostic biomarker for poor RFS and cytarabine resistance in NPM1+FLT3-ITD- AML. Further studies with the large number of patients are warranted.

P3, N=339, Not yet recruiting, Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori

P2/3, N=76, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Oct 2024 --> Oct 2025

P2, N=146, Recruiting, Technische Universität Dresden | Not yet recruiting --> Recruiting

Furthermore, there was a notable increase in ROS and MDA levels. Overall, n-3 PUFA treatment improved cytarabine's efficacy in iron-overloaded NALM-6 cells by activating apoptotic processes and oxidative stress pathways.