Leukemia & Lymphoma

Low-density lipoprotein receptor-related protein-6 (LRP6) is overexpressed in various cancers. The small molecule salinomycin sodium inhibits LRP6. We observed a higher proportion of subjects with non-germinal center B (non-GCB) subtypes having high LRP6 expression than those with GCB subtypes by immunohistochemistry. The PCR and Western blot assays demonstrated increased LRP6 expression in non-GCB subtype cells. In addition, CCK-8 assays and transwell cell migration assays revealed that salinomycin sodium exhibited dose- and time-dependent inhibition of proliferation and migration in non-GCB subtype cells...

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Ibrutinib has dramatically changed the treatment landscape for chronic lymphocytic leukemia (CLL) since its availability in British Columbia (BC), Canada in 2014. We analyzed patterns of use and real-world survival outcomes in 370 patients who received ibrutinib for first-line (1 L, n  = 35) and relapsed/refractory (R/R, n  = 335) CLL between 2014-2018 in BC. Dose reductions and interruptions were frequent in 32% and 27%, respectively. With a median follow-up of 27.6 months, 35% of patients discontinued ibrutinib, primarily for adverse events (AEs) rather than progressive disease...

Fluoroquinolones (FQ) has been used after allogeneic hematopoietic stem cell transplantation (allo-HCT) for decades. This study on 284 allo-HCT recipients aimed to analyze the impact of FQ on pre-engraftment BSI. A total of 154 patients were colonized with resistant gram-negative bacteria, and 130 patients were not. Colonized patients did not receive FQ ( n  = 147) except 7 who received FQ as sequential therapy; 98 non-colonized patients received FQ, whereas 32 did not. Gram-negative ( p  < 0...

Currently there are no guidelines on a safe neutrophil count(ANC) for intravenous antibiotic(IVAB) cessation and hospital discharge in patients recovering after febrile neutropenia(FN). We assessed the safety in selected patients after recent FN of prompt IVAB cessation and hospital discharge. Safety was defined as no fever recurrence after IVAB cessation and readmission in the 10-days post-discharge for infections.A retrospective, single center audit conducted on 92 adult hematology patients admitted with de novo acute myeloid leukemia (AML) for intensive chemotherapy or for an autograft...

Myelofibrosis (MF) is a chronic myeloproliferative neoplasm characterized by splenomegaly, abnormal cytokine expression, cytopenias, and progressive bone marrow fibrosis. The disease often manifests with burdensome symptoms and is associated with reduced survival. Ruxolitinib, an oral Janus kinase (JAK) 1 and JAK2 inhibitor, was the first agent approved for MF. As a first-in-class targeted treatment, ruxolitinib approval transformed the MF treatment approach and remains standard of care. In addition, targeted inhibition of JAK1/JAK2 signaling, a key molecular pathway underlying MF pathogenesis, and the large volume of literature evaluating ruxolitinib, have led to a better understanding of the disease and improved management in general...

The highly utilized KC model has a reported lethality rate of about 30%, which has been attributed to pancreas cancer. However, a competing cause of lethality in KC mice is due to the activation of mutant- Kras gene ( KrasG12D/+ ) in the multipotent progenitor cells (MPP), and subsequent development of Kras -mutant T-cell acute lymphoblastic leukemia (T-ALL). Overall, 20% (5/25) of KC mice developed T-ALL by 9 months of age. Transplantation of pooled bone marrow from KC mice into CD45 congenic mice caused T-ALL in 100% of recipient mice, confirming that mutant- Kras expression in the hematologic compartment is driving the development of T-ALL in the KC mouse model...

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Taurine upregulated gene 1 (TUG1) has been implicated in the onset and progression of various malignancies. The current study aimed to evaluate the biological function and potential mechanisms of TUG1 in multiple myeloma (MM) progression. TUG1 knockdown in MM cells was investigated in vitro and in vivo to evaluate the role of TUG1. We also predicted the transcription factor (TF) that bound to TUG1 together with the downstream target genes of the TUG1-TF interaction, and evaluated the regulatory mechanism of TUG1 in cell assays...

The six-year ECHELON-1 update showed a survival advantage for frontline (1 L) A + AVD (brentuximab vedotin, doxorubicin, vinblastine, dacarbazine) vs ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) for stage III/IV classic Hodgkin lymphoma (cHL). As clinical trials have limited ability to track patients for extended periods, we developed an oncology simulation model using ECHELON-1 data to estimate population-based cHL outcomes in the US over 10 years (through 2031). The model included a scenario without (64...

Upregulation of the anti-apoptotic protein MCL-1 has been implicated in chemotherapy resistance and poor clinical outcomes in B-cell lymphoma (BCL). We report the activity of AMG176, a direct, selective MCL-1 inhibitor, in preclinical models of BCL. A panel of cell lines representing diffuse large B-cell lymphoma (DLBCL), double-hit lymphoma (DHL) and Burkitt's lymphoma (BL) was selected. AMG176 induced apoptotic cell death in a dose- and time-dependent manner in all BCL cell lines. Baseline MCL-1 expression was not predictive of response...

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In this retrospective cohort study, we evaluated the level of biomarkers of inflammation like phagocyte-related S100 proteins and a panel of cytokines in 128 children with pre-B ALL and 22 with T-ALL. The biomarkers were evaluated at diagnosis and during antileukemic therapy (day 29 and after six months) and we evaluated their correlation with basic laboratory values. Further, for the children with pre-B ALL, we evaluated whether the biomarkers could predict the outcome of ALL expressed as minimal residual disease (MRD), relapse, and death...

Venetoclax (VEN) in combination with hypomethylating agents (HMA) or low-dose cytarabine has become the standard of care for patients with acute myeloid leukemia (AML) who are ineligible to receive intensive induction chemotherapy. Clinical trials are performed in a controlled setting that can be difficult to emulate in the real world. We sought to investigate outcomes of patients treated with VEN-based therapy in the real world. Patients with an age of ≥65 years who received frontline VEN-based therapy were identified using the COTA database ( n  = 112)...

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The prognostic significance of RAS mutations in AML is poorly understood. In this ambispective cohort study of 239 newly-diagnosed AML patients at the University of Maryland, we assessed the median overall survival (mOS) and median event-free survival (mEFS) in RAS wild-type (WT) AML ( n  = 196), KRAS -mutated AML ( n  = 11), NRAS -mutated AML ( n  = 25), and KRAS / NRAS -mutated AML ( n  = 7). We used propensity score to adjust outcomes. NRAS- mutated AML had a similar response rate to first-line treatment and mOS compared to RAS -WT AML (57 vs...