In vitro chemosensitivity testing of leukemic cells: Prediction of response to chemotherapy in patients with acute non-lymphocytic leukemia

1989 ◽  
Vol 7 (4) ◽  
pp. 287-293 ◽  
Author(s):  
Valeria Santini ◽  
Pietro Antonio Bernabei ◽  
Luigi Silvestro ◽  
Orietta Dal Pozzo ◽  
Roberto Bezzini ◽  
...  
Keyword(s):  
Lymphocytic Leukemia ◽  
Leukemic Cells ◽  
Prediction Of Response ◽  
Chemosensitivity Testing ◽  
In Vitro Chemosensitivity ◽  
Response To Chemotherapy

Precise Prediction of Response to Therapy by Using the Chemosensitivity Index Ci in Patients with Chronic Lymphocytic Leukemia.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2791-2791
Author(s):  
Peter Staib ◽  
Rabea Lube ◽  
Timo Schinkothe
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Response To Therapy ◽  
Lymphocytic Leukemia ◽  
Differential Staining ◽  
Chemosensitivity Test ◽  
Prediction Of Response ◽  
Chemosensitivity Testing ◽  
In Vitro Chemosensitivity ◽  
Disc Assay

Abstract There are quite a few number of prognostic factors known to determine the prognosis of patients with chronic lymphocytic leukemia (CLL). However, the individual response to therapy may still not be predicted by these factors. Therefore, we investigated prospectively the prediction of response to therapy and the prognostic relevance of the in-vitro chemosensitivity profile in patients with CLL within a randomized trial. For the evaluation of the chemosensitivity profile we applied the methodology of the chemosensitivity index Ci, which we described before in AML (Staib et al., Br J Haematol 2005). Peripheral blood samples from patients with the established diagnosis of B-CLL were taken with written informed consent before treatment was started. For in vitro chemosensitivity testing the Differential Staining Cytotoxicity (DiSC) Assay was used. The fresh leukemic cells were incubated with fludarabine, bendamustine and six other cytotoxic drugs. DiSC assay results were expressed as percent tumor cell survival (%TCS). The chemosensitivity index Ci was calculated according to dose-response curves for each clinically used drug and the area under the curve (AUC). The cut off point between resistance and sensitivity was adjusted at 0,5 for each drug by the AUC data of a subgroup of clinically resistant patients: Ci ≤0.5 indicates resistance, Ci >0.5 sensitivity to the drug. Results: 53 patients were recruited to a two-arm randomized second line treatment trial from 2001 to 2005. The patients were treated with either fludarabine or bendamustine as a monotherapy. For all patients a chemosensitivity test was performed to predict the clinical outcome for the used treatment. 25 (47%) patients received fludarabine and 28 (53%) bendamustine. 41 pts. (77%) achieved a complete or a partial remission whereas 12 pts. had a stable or progressive disease (23%). All of the responding patients were predicted as sensitive (100%), and all 12 non-responding patients were predicted as resistant (100%). The over all accuracy was 100% (Pearson Chi-square p<0.001). The progression free survival time in patients who were tested to be resistant was 4 months compared to 22 months in patients who were tested to be sensitive (p<0.001). Conclusion: The presented study demonstrates that the in-vitro chemosensitvity profile is able to predict the clinical treatment outcome in patients with CLL precisely. Therefore, the in-vitro chemosensitivity testing evaluated by the Ci may serve as a powerful tool for assay directed and individualized therapy strategies in B-CLL.

In vitro chemosensitivity testing of leukemic cells: Development of a semiautomated colorimetric assay

1989 ◽  
Vol 7 (3) ◽  
pp. 243-253 ◽  
Author(s):  
Pietro Antonio Bernabei ◽  
Valeria Santini ◽  
Luigi Silvestro ◽  
Orietta Dal Pozzo ◽  
Roberto Bezzini ◽  
...  
Keyword(s):  
Colorimetric Assay ◽  
Leukemic Cells ◽  
Chemosensitivity Testing ◽  
In Vitro Chemosensitivity

In vitro chemosensitivity testing in acute non lymphocytic leukemia using the bioluminescence ATP assay

2000 ◽  
Vol 24 (5) ◽  
pp. 445-452 ◽  
Author(s):  
Lars Möllgård ◽  
Ulf Tidefelt ◽  
Britt Sundman-Engberg ◽  
Christina Löfgren ◽  
Christer Paul
Keyword(s):  
Lymphocytic Leukemia ◽  
Chemosensitivity Testing ◽  
Atp Assay ◽  
In Vitro Chemosensitivity

The MTS vs. the ATP assay for in vitro chemosensitivity testing of primary glioma tumour culture

2010 ◽  
Vol 36 (6) ◽  
pp. 564-567 ◽  
Author(s):  
T. P. Dawson ◽  
R. V. Iyer ◽  
R. W. Lea ◽  
P. Roberts ◽  
F. Harris ◽  
...  
Keyword(s):  
Chemosensitivity Testing ◽  
Atp Assay ◽  
In Vitro Chemosensitivity ◽  
Primary Glioma

scholarly journals Interferon system in primary acute lymphocytic leukemia cells with or without deletions of the alpha-/beta-interferon genes

Blood ◽  
1992 ◽  
Vol 79 (8) ◽  
pp. 2076-2083 ◽  
Author(s):  
D Grander ◽  
M Heyman ◽  
K Brondum-Nielsen ◽  
Y Liu ◽  
E Lundgren ◽  
...  
Keyword(s):  
Acute Lymphocytic Leukemia ◽  
Lymphocytic Leukemia ◽  
Leukemic Cells ◽  
Malignant Cells ◽  
Oligoadenylate Synthetase ◽  
Gene Deletions ◽  
Functional Studies ◽  
Cell Clones ◽  
Alpha Beta

Abstract Various aspects of the interferon (IFN) system were studied in malignant cells from 37 unselected patients with acute lymphocytic leukemia (ALL). It was found that leukemic cells from two of 37 patients had a complete loss of alpha- and beta-IFN genes, whereas cells from four of 37 had lost one of the alpha-/beta-IFN alleles. In 25 cases, viable cells were also available for functional studies. Cell clones with loss of one of the alpha-/beta-IFN alleles produced low amounts of IFN after virus induction in vitro. Some clones with an apparently normal set of IFN genes were unable to produce detectable amounts of IFN. All clones studied were found to carry high-affinity alpha-IFN receptors. In clones carrying deletions of IFN genes, the cells were sensitive to IFN in vitro as measured by alpha-IFN-induced enhancement of 2′,5′-oligoadenylate synthetase (2′,5′-A synthetase). Cells from four patients with an apparently normal set of IFN genes were insensitive to this effect of IFN. We conclude that of the 17 patients in which IFN genes, IFN production, alpha-IFN receptors, and IFN-induced enhancement of 2′,5′-A synthetase were studied, nine (53%) showed some abnormality in their IFN system. This finding may add some support to the hypothesis that defects in the IFN system could be a step on the path to malignant transformation in ALL. Moreover, patients whose malignant cells carry IFN gene deletions or other defects in their IFN-producing capacity, but are still sensitive to exogenous IFN, could represent a subgroup of ALL with a greater likelihood of responding to IFN therapy.

Aberrant expression of B-lymphocyte stimulator by B chronic lymphocytic leukemia cells: a mechanism for survival

Blood ◽  
2002 ◽  
Vol 100 (8) ◽  
pp. 2973-2979 ◽  
Author(s):  
Anne J. Novak ◽  
Richard J. Bram ◽  
Neil E. Kay ◽  
Diane F. Jelinek
Keyword(s):  
B Cells ◽  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
B Lymphocyte ◽  
Leukemic Cell ◽  
Lymphocytic Leukemia ◽  
Leukemic Cells ◽  
Aberrant Expression ◽  
B Lymphocyte Stimulator

B-cell chronic lymphocytic leukemia (B-CLL) is defined by the accumulation of CD5+ B cells in the periphery and bone marrow. This disease is not characterized by highly proliferative cells but rather by the presence of leukemic cells with significant resistance to apoptosis and, therefore, prolonged survival. B-lymphocyte stimulator (BLyS) is a newly identified tumor necrosis factor (TNF) family member shown to be critical for maintenance of normal B-cell development and homeostasis and it shares significant homology with another TNF superfamily member, APRIL. The striking effects of BLyS on normal B-cell maintenance and survival raises the possibility that it may be involved in pathogenesis and maintenance of hematologic malignancies, including B-CLL. In this study, we investigated the status of APRIL and BLyS expression, as well as their receptors, in this disease. All B-CLL patient cells studied expressed one or more of 3 known receptors for BLyS; however, the pattern of expression was variable. In addition, we demonstrate for the first time that B-CLL cells from a subset of patients aberrantly express BLyS and APRIL mRNA, whereas these molecules were not detectable in normal B cells. Furthermore, we provide in vitro evidence that BLyS protects B-CLL cells from apoptosis and enhances cell survival. Because these molecules are key regulators of B-cell homeostasis and tumor progression, leukemic cell autocrine expression of BLyS and APRIL may be playing an important role in the pathogenesis of this disease.

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