FMOD expression in whole blood aids in distinguishing between chronic lymphocytic leukemia and other leukemic lymphoproliferative disorders. A pilot study

2020 ◽  
Vol 98 (5) ◽  
pp. 421-428 ◽  
Author(s):  
Marc Sorigue ◽  
Jordi Junca ◽  
Christelle Ferra ◽  
Silvia Marce ◽  
Neus Ruiz‐Xivillé ◽  
...  
Keyword(s):  
Pilot Study ◽  
Chronic Lymphocytic Leukemia ◽  
Whole Blood ◽  
Lymphoproliferative Disorders ◽  
Lymphocytic Leukemia

scholarly journals Pseudohyperkalemia in Patients with Chronic Lymphocytic Leukemia

2011 ◽  
Vol 2011 ◽  
pp. 1-3 ◽  
Author(s):  
Stephen I. Rifkin
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Blood Cell ◽  
Mechanical Stress ◽  
White Blood Cell ◽  
Whole Blood ◽  
Correct Diagnosis ◽  
Plasma Potassium ◽  
Lymphocytic Leukemia ◽  
Blood Potassium

Pseudohyperkalemia occurs occasionally in patients with extreme leukocytosis. Increased white blood cell fragility coupled with mechanical stress is felt to be causal. Serum and plasma potassium levels have been both associated with pseudohyperkalemia. Whole blood potassium determination will usually verify the correct diagnosis. It is important to diagnose this condition early so that patients are not inappropriately treated. Two patients with chronic lymphocytic leukemia and extreme leukocytosis are presented, one with pseudohyperkalemia and one with probable pseudohyperkalemia, and diagnostic considerations are discussed

scholarly journals A pilot study of lower doses of ibrutinib in patients with chronic lymphocytic leukemia

Blood ◽  
2018 ◽  
Vol 132 (21) ◽  
pp. 2249-2259 ◽  
Author(s):  
Lisa S. Chen ◽  
Prithviraj Bose ◽  
Nichole D. Cruz ◽  
Yongying Jiang ◽  
Qi Wu ◽  
...  
Keyword(s):  
Pilot Study ◽  
Chronic Lymphocytic Leukemia ◽  
Lymphocytic Leukemia ◽  
Downstream Signaling ◽  
Protein Levels ◽  
Lower Drug ◽  
Dose Dependent ◽  
Initial Cycle ◽  
Different Doses ◽  
Dose Reductions

Abstract Ibrutinib is highly efficacious and used at 420 mg/d for treatment of chronic lymphocytic leukemia (CLL). We previously demonstrated a decline in Bruton’s tyrosine kinase (BTK) protein levels in CLL cells after 1 cycle of ibrutinib, suggesting ibrutinib dose could be lowered after the first cycle without loss of biological effect. To test this postulate, a pilot study (NCT02801578) was designed to systematically reduce ibrutinib dosing within the same patient with CLL over the course of three 28-day cycles. After an initial cycle of 420 mg/d, the dose was reduced to 280 mg/d in cycle 2, and then to 140 mg/d in cycle 3. Eleven patients began study treatment, and 9 completed the 3 cycles. Plasma and intracellular pharmacokinetics (PK), BTK occupancy, and pharmacodynamic (PD) response at different doses of ibrutinib were compared. Plasma and intracellular levels of ibrutinib were dose-dependent, and even the lowest dose was sufficient to occupy, on average, more than 95% of BTK protein. In concert, BTK downstream signaling inhibition was maintained with 140 mg/d ibrutinib in cycle 3, and there were comparable reductions in total and phospho-BTK (Tyr223) protein levels across 3 cycles. Reductions of plasma chemokine CCL3 and CCL4 levels, considered to be biomarkers of ibrutinib response, were similar during the 3 cycles. These PK/PD data demonstrate that after 1 cycle of ibrutinib at the standard 420 mg/d dose, the dose can be reduced without losing biological activity. Clinical efficacy of lower doses needs to be systematically evaluated. Such dose reductions would lower drug cost, lessen untoward toxicity, and facilitate rationale-based combinations. This trial was registered at www.clinicaltrials.gov as #NCT02801578.

scholarly journals Production of tumor necrosis factor-alpha by B-cell chronic lymphocytic leukemia cells: a possible regulatory role of TNF in the progression of the disease

Blood ◽  
1990 ◽  
Vol 76 (2) ◽  
pp. 393-400 ◽  
Author(s):  
R Foa ◽  
M Massaia ◽  
S Cardona ◽  
AG Tos ◽  
A Bianchi ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Tumor Necrosis Factor ◽  
B Cell ◽  
Tumor Necrosis ◽  
Lymphoproliferative Disorders ◽  
Lymphocytic Leukemia ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Necrosis Factor ◽  
Cell Chronic Lymphocytic Leukemia

Abstract Tumor necrosis factor-alpha (TNF) is a cytokine that displays a pleomorphic array of effects on different cell populations. Evidence is presented that TNF may be constitutively produced by B-cell chronic lymphocytic leukemia (B-CLL) and hairy cell leukemia (HCL) cells and that it may play a relevant role in these diseases. These conclusions are based on the presence of circulating levels of TNF in the serum of 20 of the 24 patients tested (83.3%), while undetectable values were found in normal sera. The suggestion that the increased serum levels were due to the leukemic cell population is strengthened by the evidence that purified B-CLL and HCL cells may constitutively release variable degrees of TNF. These levels markedly increase after incubation with interferon gamma or phytohemagglutinin (PHA) plus phorbol myristate acetate (PMA). The cellular release of TNF by primary B-CLL cells was significantly (P less than .001) higher in B-CLL stage O-I patients compared with stage II-III patients. The demonstration that, in B-cell chronic lymphoproliferative disorders, the pathologic cells may release TNF was further confirmed by the presence of the mRNA for this cytokine in primary and/or in pre-activated cells. Recombinant TNF was capable of inducing a proliferative signal only in a minority of cases (4/24); in most cases it was ineffective, and, in a few, it reduced the degree of proliferation. Furthermore, in costimulatory experiments with interleukin-2 and PHA plus PMA, TNF was ineffective. On the other hand, when primary B-CLL cells were incubated in the presence of an anti-TNF antibody, in 8 of 12 independent experiments a 2- to 15-fold increase in thymidine uptake was documented. Taken together, these results suggest that TNF may play a regulatory role in the progression of the neoplastic clone in B-cell chronic lymphoproliferative disorders and may be implicated in some of the side effects associated with these diseases.

CD5+ B-cell lymphoproliferative disorders: Beyond chronic lymphocytic leukemia and mantle cell lymphoma

2010 ◽  
Vol 34 (9) ◽  
pp. 1235-1238 ◽  
Author(s):  
Dragan Jevremovic ◽  
Roxana S. Dronca ◽  
William G. Morice ◽  
Ellen D. McPhail ◽  
Paul J. Kurtin ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
Lymphoproliferative Disorders ◽  
Lymphocytic Leukemia ◽  
Mantle Cell

A pilot study of epirubicin and chlorambucil in the treatment of chronic lymphocytic leukemia (CLL)

2006 ◽  
Vol 9 (6) ◽  
pp. 315-321 ◽  
Author(s):  
G. M. Smith ◽  
J. A. Child ◽  
D. W. Milligan ◽  
M. A. McEvoy ◽  
J. A. Murray
Keyword(s):  
Pilot Study ◽  
Chronic Lymphocytic Leukemia ◽  
Lymphocytic Leukemia

Inhibition of Bortezomib-Induced Apoptosis in Chronic Lymphocytic Leukemia by Red Blood Cell Uptake.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5027-5027
Author(s):  
Luise M.C. Wheat ◽  
Susan L. Kohlhaas ◽  
Johan Monbaliu ◽  
Roland De Coster ◽  
Aneela Majid ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Whole Blood ◽  
Mononuclear Cells ◽  
Lymphocytic Leukemia ◽  
Cell Uptake ◽  
Reversible Inhibitor ◽  
Apoptotic Pathway ◽  
Mutational Status ◽  
Induced Apoptosis

Abstract Bortezomib (PS-341/Velcade™) is a reversible inhibitor of the proteasome that has shown promising activity in clinical trials in several malignancies including multiple myeloma, mantle cell lymphoma and follicular lymphoma, including those with refractory disease. However, results have been less encouraging in chronic lymphocytic leukemia (CLL) and we have, therefore, sought to determine the barriers to effective therapy with bortezomib in this disease. Patients with CLL were eligible but were required to have received no therapy in the six months prior to the study. In a panel of 26 patients with CLL, both purified mononuclear cells and whole blood were tested for their apoptotic response to bortezomib (1–100 nM) up to 24 h by flow cytometry and western blotting. In all cases, purified CLL cells were sensitive to bortezomib-induced apoptosis in a concentration and time-dependent fashion, irrespective of stage of disease, resistance to prior therapy, IGHV mutational status or the presence of TP53 mutations. Apoptosis was induced at low (>10 nM) nanomolar concentrations of bortezomib by activation of the intrinsic apoptotic pathway. Bortezomib-induced apoptosis correlated with levels of ubiquitination, Bax activation, and caspase cleavage. Apoptosis of CLL cells was obtained at drug levels readily obtained in vivo using currently-used dosing protocols. However, in vitro, it was necessary to maintain these concentrations for 16–24 hours to obtain maximal apoptosis. Apoptosis measured in a whole blood apoptosis assay was markedly less than in isolated lymphocytes at comparable time points and concentrations. Activity of bortezomib in purified cells was not diminished by addition of exogenous plasma but was abrogated by addition of autologous red blood cells (RBC), suggesting preferential active uptake of the drug by these cells. These data were confirmed in animal models showing preferential distribution of bortezomib to the RBC fraction. RBC uptake may therefore account for the low serum levels of bortezomib attained in vivo during terminal half-life and thus the lack of activity against cells in the peripheral blood. Together with pharmacokinetic and in vivo data, these studies suggest that different dosing schedules of bortezomib other than bolus injections may be more effective in patients with CLL.

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