Navigating the nexus of MRD and novel agents in ALL.
Navigating the nexus of MRD and novel agents in ALL. Hematology Am Soc Hematol Educ Program. 2019 Dec 06;2019(1):9-16 Authors: Advani AS, Copelan EA Abstract The landscape of acute lymphoblastic leukemia (ALL) has evolved significantly over the last few years. Identification of specific recurrent genetic alterations and of minimal residual disease (MRD) guides prognostic classification and management. Novel agents (eg, blinatumomab) have demonstrated encouraging results in relapsed/refractory (R/R) and MRD+ patients and are currently incorporated into upfront treatment in specific settings. Other new strategies include the incorporation of tyrosine kinase inhibitor-based therapy for patients with Philadelphia chromosome-like ALL and the use of DOT inhibitors and bcl-2/bcl-xl inhibitors in R/R disease. These innovations promise to improve management and outcome in this disease. PMID: 31808877 [PubMed - in process]
Malavasi CD22 is a surface molecule expressed early during the ontogeny of B cells in the bone marrow and spleen, and can be found on B cells isolated from the different lymphoid compartments in humans. CD22 is expressed by most blasts from the majority (60–90%) of B-cell acute lymphoblastic leukemia (B-ALL). Current therapies in adults with newly diagnosed B-ALL are associated with complete remission (CR) rates of 50–90%. However, 30–60% of these patients relapse, and only 25–40% achieve disease-free survival of three years or more. Chemotherapy regimens for patients with re...
In conclusion, prospective, rigorous, adequately powered, and high-quality longitudinal studies are urgently needed to deliver effective lifestyle interventions to children with ALL to treat and prevent obesity. These interventions, if successful, may improves cardiometabolic health outcomes and enhance the quality of life and life expectancy in children with ALL.
ConclusionWe have demonstrated that PP is a novel therapeutic lead compound that counteracts the respiratory reprogramming found in refractory ALL cells and can be effectively formulated into a nanoparticle delivery system to target the BTME.
Leukemia, Published online: 27 January 2020; doi:10.1038/s41375-020-0715-2Disease escape with the selective loss of the Philadelphia chromosome after tyrosine kinase inhibitor exposure in Ph-positive acute lymphoblastic leukemia
Chidamide induces necroptosis via regulation of c‑FLIPL expression in Jurkat and HUT‑78 cells. Mol Med Rep. 2020 Feb;21(2):936-944 Authors: Chi Z, Gao H, Liu H, Wu B, Zhang B, Gu M, Yang W Abstract T‑cell acute lymphoblastic leukemia (T‑ALL) is a hematopoietic malignancy, which is associated with a poor prognosis. It is difficult to achieve complete remission or long‑term survival with conventional chemotherapy, partly due to decreased apoptosis. However, necroptosis can serve as an alternative pathway to induce cell death. The present study investigated whether the selective histone deacetyl...
This study demonstrates the important effects of glycosylation on L-ASNase properties and opens up new possibilities to use glycosylated L-ASNases for the treatment of ALL.
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).
Patients (pts) receiving CTL019 (tisagenlecleucel) for B-ALL with high tumor burden (HTB) are at high risk for developing severe CRS. Tocilizumab, an IL-6 receptor antibody, is a vital component of severe CRS management; however, its role in preventing severe CRS is not known. We sought to determine the effectiveness of preemptive tocilizumab (PT) administration in decreasing the rate of grade (gr) 4 CRS in HTB pts.
Chimeric antigen receptor T cell (CAR-T cell) therapy has become a promising treatment for children with acute lymphoblastic leukaemia (ALL) and Non-Hodgkin lymphoma (NHL). Cytokine release syndrome (CRS) and Immune effector cell associated neurotoxicity syndrome (ICANS) are well-documented serious side-effects of CAR-T cell therapy, and early recognition, intervention and aggressive supportive therapy is paramount.Tociluzimab is the mainstay of treatment for moderate to severe CRS, with early administration essential.