Venetoclax added to CLAG regimen might improve the outcome of patients with relapsed/refractory acute myeloid leukemia.

Background: We aim to analyze the efficacy and safety of Venetoclax (Ven) added to cladribine + cytarabine + granulocyte colony-stimulating factor (G-CSF) ± idarubicin or mitoxantrone (CLAG ± Ida/Mito) regimen as a salvage treatment of relapsed/refractory acute myeloid leukemia (RR-AML).

Methods: A single-center, retrospective, cohort study was performed. Patients with RR-AML, being treated with CLAG ± Ida/Mito with versus without Ven, were retrospectively studied.

Targeting ceramide transfer protein sensitizes AML to FLT3 inhibitors via a GRP78-ATF6-CHOP axis.

Sphingolipid, ceramide for example, plays an essential role in regulating cancer cell death. Defects in the generation and metabolism of ceramide in cancer cells contribute to tumor cell survival and resistance to chemotherapy. Ceramide Transfer Protein (CERT) determines the ratio of ceramide and sphingomyelin in cells.

Homoharringtonine Added to Venetoclax and Azacitidine Improves Outcome and Mitigates Genetic Impact in Relapsed/Refractory AML: A Multicenter Cohort Study.

Purpose: We investigated whether homoharringtonine (HHT) added to venetoclax plus azacitidine (VA) could improve outcomes and counteract the negative effects of genetic patterns in patients with relapsed/refractory acute myeloid leukemia (RR-AML).

Experimental Design: A multicenter retrospective cohort study of the response and genetic patterns of response to the VA plus HHT (VAH) versus the VA regimens as salvage treatment in patients with RR-AML was performed. The endpoints were the rates of composite complete remission, measurable residual disease, event-free survival, overall survival, and relapse between VAH and VA groups.

Homoharringtonine sensitized resistant acute myeloid leukemia cells to venetoclax-induced apoptosis.

Venetoclax (VEN), a B-cell lymphoma 2 (BCL-2) selective inhibitor, is widely used for treating acute myeloid leukemia (AML) with promising results. However, the anti-leukemic effect of VEN in relapsed/refractory (R/R)- AML requires improvement. In this study, we observed that combining homoharringtonine (HHT) with VEN plus azacitidine resulted in a significantly higher response and better survival than VA alone in patients with R/R-AML.

Trafficking circuit of CD8 T cells between the intestine and bone marrow governs antitumour immunity.

Immunotherapy elicits a systemic antitumour immune response in peripheral circulating T cells. However, the T cell trafficking circuit between organs and their contributions to antitumour immunity remain largely unknown. Here we show in multiple mouse leukaemia models that high infiltration of leukaemic cells in bone marrow (BM) stimulates the transition of CD8CD44CD62L central memory T cells into CD8CD44CD62L T cells, designated as inter-organ migratory T cells (T cells).

Impact of different CEBPA mutations on therapeutic outcome in acute myeloid leukemia.

Biallelic mutations of the CEBPA gene (CEBPA) are generally associated with favorable prognosis in patients with acute myeloid leukemia (AML). Monoallelic mutations of the CEBPA gene in carboxy-terminal DNA-binding region (CEBPA) and amino-terminal transactivation domains (CEBPA) indicate distinct clinical characteristics and therapeutic outcomes. However, further investigation is required to fully understand these differences.

Homoharringtonine may help improve the outcomes of venetoclax and azacitidine in AML1-ETO positive acute myeloid leukemia.

Purpose: T(8;21)(q22;q22.1)/AML1-ETO positive acute myeloid leukemia (AE-AML) is sensitive to conventional chemotherapy with a favorable prognosis. However, recent small case reports suggest the limited effectiveness of venetoclax (VEN) and hypomethylating agents (HMA) in treating AE-AML.

Decreasing circ_0014614 promotes the differentiation of bone marrow flineage cells into megakaryocytes in essential thrombocythemia via activiation of miR-138-5p/caspase3 axis.

Background: Circular RNAs (circRNA) are pivotal in hematological diseases. Previous study showed that circ_0014614 (circDAP3) was significantly underexpressed in bone marrow-derived exosomes from essential thrombocythemia (ET) patients, affecting the differentiation of bone marrow lineage cells into megakaryocytes.

Methods: Fluorescence in situ hybridization (FISH) was used to display circ_0014614's primary cytoplasmic location in K562 cells.

Impact of measurable residual disease in combination with CD19 on postremission therapy choices for adult t(8;21) acute myeloid leukemia in first complete remission.

Background: The post-remission therapy (PRT) choices for adult t(8;21) acute myeloid leukemia (AML) in first complete remission (CR1) need to be further explored.

Aims: We aimed to investigate the impact of measurable residual disease (MRD) combined with CD19 on PRT choices for adult t(8;21) AML in CR1.

Methods: A total of 150 t(8;21) AML patients were enrolled, including 67 underwent chemotherapy (CMT) and 83 allogeneic hematopoietic stem cell transplantation (allo-SCT) as PRT in CR1.

Clinical and genetic characteristics predict outcomes of acute myeloid leukemia patients with FLT3 mutations receiving venetoclax-based therapy.

Background: Acute myeloid leukemia (AML) is a heterogeneous disease, and its heterogeneity is associated with treatment response. Despite the demonstrated success of venetoclax (VEN)-based therapy for AML, the effect of FLT3 mutations on the efficacy of the therapy is poorly understood. We aimed to compare the efficacy of VEN-based therapy between FLT3-mutated (FLT3 ) and FLT3 wild-type (FLT3 ) patients and identify the predictors of efficacy in FLT3 patients.

Changing epidemiology, microbiology and mortality of bloodstream infections in patients with haematological malignancies before and during SARS-CoV-2 pandemic: a retrospective cohort study.

Objective: This study was to explore the changes in bacterial bloodstream infection (BSI) in patients with haematological malignancies (HMs) before and during SARS-CoV-2 pandemic.

Design: Retrospective cohort study between 2018 and 2021.

Setting: The largest haematological centre in southern China.

Sorafenib plus triplet therapy with venetoclax, azacitidine and homoharringtonine for refractory/relapsed acute myeloid leukemia with FLT3-ITD: A multicenter phase 2 study.

Background: Patients with relapsed or refractory acute myeloid leukemia (R/R AML) and FLT3-internal tandem duplication (FLT3-ITD) respond infrequently to salvage chemotherapy.

Objective: To investigate the efficacy of sorafenib plus triplet therapy with venetoclax, azacitidine, and homoharringtonine (VAH) as a salvage therapy in this population.

Methods: This multicenter, single-arm, phase 2 study was conducted at 12 hospitals across China.

Hypomethylating agents plus modified priming regimens compared with venetoclax-based regimens based on molecular characteristics for newly diagnosed patients with acute myeloid leukemia: a multi-center cohort study.

Venetoclax (VEN)-based regimens are the standard of care for elderly or unfit patients with newly diagnosed (ND) acute myeloid leukemia (AML). Some single-arm studies have implied that hypomethylating agents (HMAs) plus priming regimens may potentially provide an alternative therapeutic approach, owing to encouraging efficacy seen. However, no comparative data exists yet regarding these two treatment approaches.

Identifying prognostic biomarker related to immune infiltration in acute myeloid leukemia.

The immune cells of tumor microenvironment (TME) constitute a vital element of the tumor tissue. There is increasing evidence for their clinical significance in predicting prognosis and therapeutic outcomes. However, the TME immune cell infiltrating pattern of the bone marrow in acute myeloid leukemia (AML) patients remains unclear.

Venetoclax Combined with Azacitidine and Homoharringtonine in Relapsed/Refractory AML: A Multicenter, Phase 2 Trial.

Background: Relapsed or refractory acute myeloid leukemia (R/R AML) has a dismal prognosis. The aim of this study was to investigate the activity and tolerability of venetoclax combined with azacitidine plus homoharringtonine (VAH) regimen for R/R AML.

Methods: This phase 2 trial was done at ten hospitals in China.

The multi-kinase inhibitor CG-806 exerts anti-cancer activity against acute myeloid leukemia by co-targeting FLT3, BTK, and Aurora kinases.

Background: Despite the development of several FLT3 inhibitors that have improved outcomes in patients with FLT3-mutant acute myeloid leukemias (AML), drug resistance is frequently observed, which may be associated with the activation of additional pro-survival pathways such as those regulated by BTK, aurora kinases, and potentially others in addition to acquired tyrosine kinase domains (TKD) mutations of gene. may not always be a driver mutation.

Objective: To evaluate the anti-leukemia efficacy of the novel multi-kinase inhibitor CG-806, which targets FLT3 and other kinases, in order to circumvent drug resistance and target wild-type (WT) cells.

Genetic characteristics predict response to venetoclax plus hypomethylating agents in relapsed or refractory acute myeloid leukemia.

Background: The heterogeneity of relapsed or refractory (R/R) acute myeloid leukemia (AML) leads to no response to venetoclax (VEN)-based therapy in more than half of the patients. Genetic characteristics are considered important predictors for response to treatment in adults with AML. However, the association of genetic characteristics with outcomes receiving VEN-based therapy is incompletely understood in R/R AML.

Concomitant targeting of FLT3 and BTK overcomes FLT3 inhibitor resistance in acute myeloid leukemia through the inhibition of autophagy.

Strategies to overcome resistance to FMS-like tyrosine kinase 3 (FLT3)-targeted therapy in acute myeloid leukemia (AML) are urgently needed. We identified autophagy as one of the resistance mechanisms, induced by hypoxia and the bone marrow microenvironment via activation of Bruton tyrosine kinase (BTK). Suppressing autophagy/BTK sensitized FLT3- mutated AML to FLT3 inhibitor-induced apoptosis.

Autophagy activation mediates resistance to FLT3 inhibitors in acute myeloid leukemia with FLT3-ITD mutation.

Background: Autophagy plays a critical role in drug resistance in acute myeloid leukemia (AML), including the subtype with FLT3-ITD mutation. Yet how autophagy is activated and mediates resistance to FLT3 inhibitors in FLT3-ITD-positive AML remains unsure.

Methods: We detected the expression of autophagy markers in FLT3-ITD-positive leukemic cells after vs.

Single-cell RNA sequencing to explore composition of peripheral blood NK cells in patients with chronic myeloid leukemia in treatment-free remission.

This study was to explore the role of NK cell subsets and gene expression in maintaining TFR status. We identified six types of NK cells in the PBMCs over both groups (healthy controls and patients with TFR). Gene Oncology analysis showed that up regulated genes were enriched in the categories of "immune response," "reaction to tumor cells," and "cytolysis.

A phase 2 study of sorafenib combined with conventional therapies in refractory central nervous system leukemia.

Background: Patients with refractory central nervous system leukemia (CNSL) have a dismal prognosis and lack effective therapy. Case reports have shown that sorafenib is effective against brain metastases, including leukemia.

Methods: To explore the efficacy of sorafenib combined with conventional therapies for refractory CNSL, a phase 2 study was conducted.

Cidofovir, a choice for salvage treatment of cytomegalovirus infection in patients with haploidentical hematopoietic stem cell transplantation.

Background: Cidofovir (CDV) is a nucleotide analogue with broad antiviral activities. It remains unclear about the CDV administration for anti-cytomegalovirus (CMV) treatment in patients with haploidentical hematopoietic stem cell transplantation (haplo-HSCT).

Patients And Methods: In this study, 31 out of 101 haplo-HSCT recipients who suffered CMV infection in the CT group (conventional treatment) were enrolled into the CDV-ST group (CDV second-line treatment).

Dynamic assessment of measurable residual disease in favorable-risk acute myeloid leukemia in first remission, treatment, and outcomes.

We aimed to investigate outcomes of different post-remission treatment (PRT) choices based on dynamic measurable residual disease (MRD) by multiparameter flow cytometry in favorable-risk AML (FR-AML). Four hundred and three younger patients with FR-AML in first complete remission (CR1) were enrolled in this registry-based cohort study, including 173 who received chemotherapy (CMT), 92 autologous stem cell transplantation (auto-SCT), and 138 allogeneic SCT (allo-SCT). The primary endpoint was the 5-year overall survival (OS).