Clinical and laboratory changes induced by alpha interferon in chronic lymphocytic leukemia-a pilot study

1987 ◽  
Vol 24 (4) ◽  
pp. 341-350 ◽  
Author(s):  
M. Talpaz ◽  
M. Rosenblum ◽  
R. Kurzrock ◽  
J. Reuben ◽  
H. Kantarjian ◽  
...  
Keyword(s):  
Pilot Study ◽  
Chronic Lymphocytic Leukemia ◽  
Lymphocytic Leukemia ◽  
Alpha Interferon ◽  
Laboratory Changes

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.

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

Validation of CLL FISH Panel Scoring by Members of the Chronic Lymphocytic Leukemia Research Consortium.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1067-1067
Author(s):  
Stephanie A. Smoley ◽  
Daniel L. Van Dyke ◽  
Neil E. Kay ◽  
Nyla A. Heerema ◽  
Marie L. dell’ Aquila ◽  
...  
Keyword(s):  
Pilot Study ◽  
Chronic Lymphocytic Leukemia ◽  
Proficiency Test ◽  
Collaborative Study ◽  
Lymphocytic Leukemia ◽  
International Standards ◽  
Pilot Studies ◽  
Trisomy 12 ◽  
Research Consortium ◽  
Local Protocol

Abstract Fluorescence in situ hybridization (FISH) probes and analysis methods for B-cell Chronic Lymphocytic Leukemia (CLL) vary extensively among cytogenetic laboratories. This is not unexpected, as neither national nor international standards have been established for most FISH studies. Lack of standardization is problematic when data collected at multiple institutions are used for clinical correlative studies. To circumvent such problems, the five participating laboratories in the CLL Research Consortium (CRC) designed and executed a joint CLL FISH validation study. Methods: Initially a survey was sent to assess equipment, methods and experience with FISH for CLL. In a pilot study to compare laboratory performance in scoring patient samples, slides from ten patients were prepared and sent to each participating lab to be hybridized with five probe sets (= 50 hybridizations) and analyzed according to their local protocol. In a second pilot study, slides from two patient samples and identical probe sets were sent to the participating labs where hybridization and analysis were carried out according to their local protocol. Next, technologists and directors from all participating labs attended a workshop where technologists working in pairs scored nuclei together, techniques and scoring criteria were established, and consensus reached on other concerns. In a proficiency test nine months after the workshop, slides from two patient samples (10 hybridizations) were hybridized and scored according to each lab’s protocol and results shared using a common reporting form. Results: Survey results indicated that four labs used the same commercially available CLL FISH panel, and one used a combination of probes from the same vendor plus several home-brew probes. Each lab scored between 100 and 200 nuclei per hybridization site, and each independently set normal cutoff values. The FISH panel included probes to detect 11q, 13q, and 17p deletions, trisomy 12, and IGH gene rearrangement. One lab included probes to detect 6q deletion. In the first pilot study each lab used their hybridization methods, probe sets, and scoring criteria. Differences among labs were observed due to variations in probe strategy, reporting of anomalies, and perhaps most important, scoring criteria. Probe strategy differences resulted in variable reporting of 11q- vs monosomy 11 and 12q duplication vs trisomy 12. Some participants reported 13q-x1 and 13q-x2 as subclones and some reported only 13q-. One lab reported an IGH rearrangement whereas the others scored IGH as normal. In the second pilot study each lab used the same methods and probe sets to facilitate comparison of scoring by the technologists. All labs correctly identified the abnormalities, and there were no false positive results. Minor scoring differences were attributed to variation in scoring criteria or inexperience with an unfamiliar FISH probe strategy. The proficiency test that followed the workshop demonstrated 100% concordance in identification of abnormalities. Inter-lab scoring was much improved compared to the first pilot study. The only exceptions were a 13q- range of 72–90% in one case, and a 17p- range of 38–67% in another case. Conclusion: The pilot studies identified a need to develop common scoring criteria. The subsequent workshop and proficiency test demonstrated that the collaborative effort resulted in more standardized scoring among the CRC laboratories. Our collaborative study emphasizes the need to establish rigorous standards and guidelines for FISH procedures and scoring criteria. Standardization of FISH methods among participating laboratories will enhance the confidence in FISH studies for both clinical applications and cooperative intergroup clinical research.

Alemtuzumab Depletes Dendritic Cells More Effectively in Blood Than in Skin: A Pilot Study in Patients With Chronic Lymphocytic Leukemia

2007 ◽  
Vol 83 (9) ◽  
pp. 1268-1272 ◽  
Author(s):  
Susanne Auffermann-Gretzinger ◽  
Lars Eger ◽  
Johannes Schetelig ◽  
Martin Bornh??user ◽  
Falk Heidenreich ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Pilot Study ◽  
Chronic Lymphocytic Leukemia ◽  
Lymphocytic Leukemia

**107 Monitoring of Innate Cellular Immune Responses in Chronic Lymphocytic Leukemia (CLL)-A Pilot Study

2011 ◽  
Vol 11 ◽  
pp. S121-S122
Author(s):  
Russell E. Lewis ◽  
William G. Wierda ◽  
Alessandra Ferrajoli ◽  
Ronen Ben-Ami ◽  
Stacie Wright ◽  
...  
Keyword(s):  
Pilot Study ◽  
Chronic Lymphocytic Leukemia ◽  
Immune Responses ◽  
Lymphocytic Leukemia ◽  
Cellular Immune Responses ◽  
Cellular Immune

scholarly journals Next-Generation Sequencing Targeted Chronic Lymphocytic Leukemia Panel: A Pilot Study

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 19-19
Author(s):  
Mariia Mikhaleva ◽  
Irina Martynkevich ◽  
Sergey Petrov ◽  
Ilya Buldakov ◽  
Alexey Kuvshinov ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Pilot Study ◽  
Chronic Lymphocytic Leukemia ◽  
Clinical Significance ◽  
Lymphocytic Leukemia ◽  
Next Generation ◽  
Mutational Status ◽  
Prognostic Groups ◽  
Treatment Naïve ◽  
Generation Sequencing

Background: Rapid progress in next-generation sequencing (NGS) technologies make it possible to spell out the mutational status, the genetic and epigenetic variability of chronic lymphocytic leukemia (CLL). The identification of driver mutations allows us to expand understanding of the pathogenesis of CLL, to identify prognostic groups and to select potential targets for therapy, contributing to the development and implementation of new targeted drugs and its combinations. Nevertheless, the course of CLL does not always correspond to the existing prognostic risk groups, assessed by "standard" cytogenetic and molecular genetic methods. The NGS technology admits establishing markers of an unfavorable course of the disease. Aim: To assess the mutational status of patients (pts) with CLL using the developed Lymphoid Targeted NGS Panel and to study the possible correlation of the mutational status with the clinical characteristics of the disease. Method: In this prospective study were included 24 pts with CLL: treatment-naïve (n=8) and relapsed/refractory (n=16). The diagnosis of CLL was established according to iwCLL criteria (iwCLL, Hallek et al., 2018) and show only typical immunophenotype. The pts were divided into three prognostic groups according to cytogenetic assay: favorable (n=14), neutral (n=2), and unfavorable (n=8). Although, 20/24 pts were divided into two prognostic groups taking into account the data on the mutational status of the immunoglobulin heavy-chain variable (IGHV) region: favorable (n=8) and unfavorable (n=12). Four patients have no available data on IGHV mutational status. All patients had indications for starting treatment: FCR (n=7), RB (n=6), ibrutinib (n=3), venetoclax (n=1), acalabrutinib (n=5), combination of venetoclax and acalabrutinib (n=2). DNA samples were extracted from peripheral B-cell lymphocytes via the standard phenol-chloroform method. Average reading depth of 1000x is produced on a MiSeq platform (Illumina, USA). The 2% threshold of allele frequency (VAF) was used. The clinical significance of mutations was established using the following databases: COSMIC, ClinVar, gnomAD with application in silico analysis (Cscape, Cancer Genome Interpreter, SNPs&Go). The Lymphoid Panel includes 117 genes, part of which is involved in the main 8 cellular signaling pathways underlying the pathogenesis of CLL. We have completed a pilot NGS study using the developed Lymphoid Targeted Gene Panel on DNA samples of six treatment-naïve pts. Results: Genetic aberrations were identified in all DNA samples using NGS. Somatic mutations were detected in 82.9% of cases, in an amount from 15 to 37. In four pts (4/6) with an unfavorable prognosis (cytogenetics and unmutated IGHV), known pathogenic variants of mutations were identified: JAK3 V722L, NOTCH1 P2514fs*4, IDH2 T352P, TP53 Lys120Glu, BRAF D594G. The existing approach to the interpretation of the results does not allow making an unambiguous conclusion about the clinical significance of variants in the IDH2 and JAK3 genes, despite the known pathogenic effect of the variants. The detected variant of the mutation (Lys120Glu) in the TP53 gene is often associated with the presence of a 17p13 deletion, which was confirmed by the FISH assay and correlated with the unfavorable clinical course of the disease in patient CLL-024. Twenty-two mutations were identified, the pathogenicity of which has not yet been determined, in the amount of 2 to 5 (median=3.5) mutations per patient. It should be noted that two patients (CLL-023, CLL-024) with unfavorable prognosis had mutations both in BCR gene and in NOTCH2 gene of unknown significance. Conclusion: The data obtained from a pilot study demonstrate the possibility of using NGS technology in clinical practice. The assessment of the mutational status of pts with CLL using NGS correlates with the clinical parameters of pts. Considering that there is currently no information about prognostic significances of identified mutations, additional research is required. Disclosures Martynkevich: Pfizer: Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau; BMS: Honoraria, Speakers Bureau. Shuvaev:Pfizer: Honoraria, Speakers Bureau; BMS: Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau. Voloshin:Novartis: Honoraria, Speakers Bureau.

Estrogen and Progesterone Receptor Guideline for Tamoxifen Therapy in Chronic Lymphocytic Leukemia: A Pilot Study

1986 ◽  
Vol 75 (2) ◽  
pp. 92-95 ◽  
Author(s):  
A. Zaniboni ◽  
Di Lorenzo ◽  
E. Simoncini ◽  
P. Marpicati ◽  
F. Gorni ◽  
...  
Keyword(s):  
Pilot Study ◽  
Chronic Lymphocytic Leukemia ◽  
Progesterone Receptor ◽  
Tamoxifen Therapy ◽  
Lymphocytic Leukemia ◽  
Estrogen And Progesterone Receptor
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