scholarly journals Fludarabine Treatment of Patient with Chronic Lymphocytic Leukemia Induces a Digital Ischemia

2016 ◽  
Vol 2016 ◽  
pp. 1-3
Author(s):  
Utku Erdem Soyaltin ◽  
Deniz Yuce Yildirim ◽  
Mustafa Yildirim ◽  
Mehmet Can Ugur ◽  
Ferhat Ekinci ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Raynaud’S Phenomenon ◽  
Raynaud's Phenomenon ◽  
Sudden Onset ◽  
Lymphocytic Leukemia ◽  
Right Hand ◽  
Digital Ischemia ◽  
Fourth Cycle ◽  
History Of

We report a 63-year-old man with a history of chronic lymphocytic leukemia (CLL) who presented with asymmetrical Raynaud’s phenomenon of sudden onset which progressed to acral gangrene rapidly in a week. These symptoms began approximately one week after the fourth cycle of fludarabine and cyclophosphamide chemotherapy and were accompanied by pain, numbness, and cyanosis in the fingers of his right hand except the first finger. Fludarabine may play a role in acral vascular syndrome. The treatment with fludarabine in patients with evolving digital ischemia should be carried out with caution.

scholarly journals The Role of Bruton’s Kinase Inhibitors in Chronic Lymphocytic Leukemia: Current Status and Future Directions

2021 ◽  
Author(s):  
Tadeusz Robak ◽  
Magda Witkowska ◽  
Piotr Smolewski
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Adverse Effects ◽  
Kinase Inhibitors ◽  
Clinical History ◽  
Lymphocytic Leukemia ◽  
Current Status ◽  
Covalent Inhibitors ◽  
History Of ◽  
Reduced Toxicity ◽  
Btk Inhibitors

The use of the Bruton’s tyrosine kinase (BTK) inhibitors has changed the management and clinical history of patients with chronic lymphocytic leukemia (CLL). BTK is a critical molecule that interconnects B-cell antigen receptor (BCR) signaling. BTKIs are classified into two categories: irreversible (covalent) inhibitors and reversible (non-covalent) inhibitors. Ibrutinib is the first irreversible BTK inhibitor approved by the U.S. Food and Drug Administration in 2013 as a breakthrough therapy in CLL patients. Subsequently, several studies evaluated the efficacy and safety of new agents with reduced toxicity when compared with ibrutinib. Two other irreversible, second-generation BTK inhibitors, acalabrutinib and zanubrutinib, were developed to reduce ibrutinib-mediated adverse effects. Additionally, new reversible BTK inhibitors are currently under development in an early phase studies to improve their activity and to diminish adverse effects. This review summarizes the pharmacology, clinical efficacy, safety, dosing, drug-drug interactions associated with the treatment of CLL with BTK inhibitors, and examines its further implications.

scholarly journals Advances in the biology and treatment of B-cell chronic lymphocytic leukemia

Blood ◽  
1995 ◽  
Vol 85 (2) ◽  
pp. 307-318 ◽  
Author(s):  
S O'Brien ◽  
A del Giglio ◽  
M Keating
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Residual Disease ◽  
Autologous Bone Marrow ◽  
Marrow Transplant ◽  
Lymphocytic Leukemia ◽  
Western Hemisphere ◽  
Molecular Heterogeneity ◽  
Prognostic Information ◽  
New Agents ◽  
History Of

Chronic lymphocytic leukemia (CLL) is the most common type of leukemia in the western hemisphere. Diagnosis and staging of CLL are usually straightforward, but predicting an individual patient's prognosis is still a challenge. Cytogenetic abnormalities provide important prognostic information in CLL and may show its molecular heterogeneity. A search for oncogene abnormalities continues, although no consistent defects have been identified. New agents such as fludarabine produce high complete remission rates and have generated interest in earlier treatment as a first step in a potential cure. Fludarabine also makes autologous bone marrow transplant feasible as a consolidation therapy. Immunologic abnormalities and minimal residual disease persist in most patients in remission. Combining fludarabine with other active agents and devising effective postremission strategies may change the natural history of CLL.

scholarly journals Chronic Lymphocytic Leukemia in Kuwait

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5467-5467
Author(s):  
Salem Alshemmari ◽  
Ramesh Pandita ◽  
Abdulaziz Hamadah ◽  
Ahmad Alhuraiji
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Board Of Directors ◽  
Mutational Analysis ◽  
Staging System ◽  
Lymphocytic Leukemia ◽  
Advisory Committees ◽  
Western Countries ◽  
Mutational Status ◽  
Study Results ◽  
History Of

Background :Chronic lymphocytic leukemia (CLL) is common malignancy in Western countries. However, little known about this disease entity in our area. This study exploring the biology in out patients' population. Method:Patients with confirmed CLL under IGHV and TP53 mutational analysis at presentation or during follow up. We also integrated other clinical and biological parameter in this study. Results: A total of 137 cases were analyzed, median age 61 years (range:34-89); 30% of the cases age was<55 years at presentation. There was 108 males vs. 29 females M:F ratio 3.7. Two patients gave a family history of CLL, while 1 patient gave a history of other lymphoproliferative disorders. Binet staging system available in 134 cases, A: 109 (81.3%), B: 12 (9%), C:13 (9.7%). B2 macroglobulin elevated in 40/112 (36%) cases and 10/103 (10%) had M-spike. CD38 positivity reported in 37/112 (33%) of cases. Cytogenetics data evaluable in 85 cases: isolated del(13q): 35%, isolated trisomy 12 (16.5%), del(11q) (4.5%), del(17p)(2.4%). IGHV mutational status mutated vs unmutated: 40% vs 60%. Cases with available treatment information on 132 cases. Fifty cases required treatment due to disease progression. First line treatment Bendamustine-Rituximab (BR) 3 cases, Fludarabine Cyclophosphamide Rituximab (FCR) 30 cases and Chlorambucil with anti-CD 20 antibody 6 cases. At the time of review, 3 cases on ibrutinib (2 in 3rdline and 1 case in the 4thline). Conclusion: This is the first study to shed light on CLL in our area. There are biological differences between our patients' population and the western countries. Disclosures Pandita: Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen Cilag: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees.

scholarly journals Tumor evolutionary directed graphs and the history of chronic lymphocytic leukemia

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Jiguang Wang ◽  
Hossein Khiabanian ◽  
Davide Rossi ◽  
Giulia Fabbri ◽  
Valter Gattei ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Evolutionary History ◽  
Directed Graphs ◽  
Evolutionary Process ◽  
Genetic Alterations ◽  
Lymphocytic Leukemia ◽  
Cross Sectional ◽  
History Of ◽  
Evolutionary Paths ◽  
Clonal Replacement

Cancer is a clonal evolutionary process, caused by successive accumulation of genetic alterations providing milestones of tumor initiation, progression, dissemination, and/or resistance to certain therapeutic regimes. To unravel these milestones we propose a framework, tumor evolutionary directed graphs (TEDG), which is able to characterize the history of genetic alterations by integrating longitudinal and cross-sectional genomic data. We applied TEDG to a chronic lymphocytic leukemia (CLL) cohort of 70 patients spanning 12 years and show that: (a) the evolution of CLL follows a time-ordered process represented as a global flow in TEDG that proceeds from initiating events to late events; (b) there are two distinct and mutually exclusive evolutionary paths of CLL evolution; (c) higher fitness clones are present in later stages of the disease, indicating a progressive clonal replacement with more aggressive clones. Our results suggest that TEDG may constitute an effective framework to recapitulate the evolutionary history of tumors.

Lack of TIR8/SIGIRR triggers progression of chronic lymphocytic leukemia in mouse models

Blood ◽  
2011 ◽  
Vol 118 (3) ◽  
pp. 660-669 ◽  
Author(s):  
Maria Teresa Sabrina Bertilaccio ◽  
Giorgia Simonetti ◽  
Antonis Dagklis ◽  
Martina Rocchi ◽  
Tania Veliz Rodriguez ◽  
...  
Keyword(s):  
Immune Response ◽  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Adaptive Immune Response ◽  
Lymphocytic Leukemia ◽  
Fine Tuning ◽  
Terminal Phase ◽  
Lymphoid Malignancies ◽  
History Of ◽  
Molecular Patterns

Abstract Inflammation is involved in the initiation and progression of several chronic lymphoid malignancies of B-cell type. Toll-like receptors (TLR) are transmembrane inflammatory receptors that on recognition of pathogen-associated molecular patterns trigger an innate immune response and bridge the innate and adaptive immune response by acting as costimulatory signals for B cells. Fine tuning of TLR and IL-1R–like (ILR) activity is regulated by TIR8 (SIGIRR), a transmembrane receptor of the TLR/ILR family which inhibits other family members. To test the hypothesis that TLR and/or ILR may play a role in the natural history of chronic B-cell tumors, we crossed Eμ-TCL1 transgenic mice, a well established model of chronic lymphocytic leukemia (CLL), with mice lacking the inhibitory receptor TIR8 that allow an unabated TLR-mediated stimulation. We here report that in the absence of TIR8 the appearance of monoclonal B-cell expansions is accelerated and mouse life span is shortened. The morphology and phenotype of the mouse leukemic expansions reproduce the progression of human CLL into an aggressive and frequently terminal phase characterized by the appearance of prolymphocytes. This study reveals an important pathogenetic implication of TLR in CLL development and progression.

Abstract 19443: Riociguat for the Treatment of Raynaud’s Phenomenon: A Single-dose, Double-blind, Randomised, Placebo-controlled Cross-over Study (DIGIT)

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Michael Huntgeburth ◽  
Johannes Kieβling ◽  
Gerrit Weimann ◽  
Verena Kiepsel ◽  
Soundos Saleh ◽  
...  
Keyword(s):  
Soluble Guanylate Cyclase ◽  
Cold Water ◽  
Raynaud’S Phenomenon ◽  
Raynaud's Phenomenon ◽  
Laser Speckle ◽  
Drug Intake ◽  
Symptom Duration ◽  
Small Pilot Study ◽  
Study Drug Administration ◽  
Digital Ischemia

Background: Raynaud’s phenomenon (RP) is a digital ischemia caused by vasoconstriction in the digital blood vessels. Triggers of RP include cold and stress. Medical therapy for RP is unsatisfactory, with many patients not responding to treatment. Here we investigated the safety, efficacy and pharmacokinetics of riociguat, a soluble guanylate cyclase stimulator, in patients with RP. Methods: Patients who had primary RP or secondary RP associated with systemic sclerosis (SSc), and a symptom duration of ≥1 year, were randomized to receive a single oral dose of riociguat 2 mg or placebo. Digital blood flow (DBF) in the right index finger was determined by Laser Speckle Contrast Analysis at room temperature (RT) and after 5 minutes of cold water exposure (CWE), both at baseline and 2 hours after study drug administration. Results: In the patients valid for evaluation (n=20), treatment with riociguat led to an increase in DBF versus baseline of 40.6% at RT and 15.1% after CWE. Based on predefined criteria, patients were considered responders if the placebo-corrected DBF after CWE increased by ≥10% versus baseline at 2 hours after drug intake. This was the case in 12/20 (60%) patients. The highest response rates were seen in patients with primary RP and limited cutaneous SSc, whereas patients with RP associated with diffuse cutaneous SSc responded less well. In responders, riociguat led to an increase in DBF versus baseline of 135.7% at RT and 38.9% after CWE. Riociguat Cmax (SD) 2 hours after drug intake was 76 (1.5) μg/ml, which is in the range previously seen in healthy volunteers and patients with pulmonary hypertension. Comparable Cmax values were observed in responders (81 [1.5] μg/ml) and non-responders (71 [1.6] μg/ml). AEs were reported in 5 patients receiving riociguat (headache, n=4; dyspepsia, n=1) and 1 patient receiving placebo (malaise). No serious AEs were reported. Conclusions: In this small pilot study, riociguat was well tolerated in patients with primary and secondary RP, and improved DBF versus placebo in 60% of patients after cold exposure.

scholarly journals Concurrent Squamous Cell Carcinoma and Chronic Lymphocytic Leukemia Presenting as an Enlarging Neck Mass

2019 ◽  
Vol 7 ◽  
pp. 232470961984290
Author(s):  
Prabhjot Bhinder ◽  
Michael Chahin ◽  
Lara Zuberi
Keyword(s):  
Squamous Cell Carcinoma ◽  
Chronic Lymphocytic Leukemia ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Neck Mass ◽  
Lymphocytic Leukemia ◽  
Secondary Malignancies ◽  
Increased Risk ◽  
History Of ◽  
Tonsillar Squamous Cell Carcinoma

Chronic lymphocytic leukemia (CLL) patients are at an increased risk for developing more aggressive lymphomas via Richter’s transformation and of developing secondary malignancies. Despite the known association for secondary cancers, oropharyngeal cancers occur rarely. We present a case of a woman with a history of CLL who presented to our facility via transfer for impending airway compromise. Her initial workup was consistent with CLL; however, biopsies were taken of the neck mass because of its aggressive nature. She was treated with rituximab with good response. Final pathology showed evidence of CLL and tonsillar squamous cell carcinoma (SCC). Direct laryngoscopy and further biopsies yielded a diagnosis of unresectable oropharyngeal SCC. She was to be treated with chemotherapy and radiation for her SCC while holding treatment for CLL. This case demonstrates a rare and unexpected concurrent diagnosis.

Peripheral T-Cell Lymphoma Arising in Patients With Chronic Lymphocytic Leukemia

2019 ◽  
Vol 152 (6) ◽  
pp. 818-827
Author(s):  
Bianca M Van Der Nest ◽  
Connull Leslie ◽  
David Joske ◽  
Dejan Radeski ◽  
Rohen White ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Cell Lymphoma ◽  
Large Cell ◽  
Lymphocytic Leukemia ◽  
Emission Tomography ◽  
Peripheral T Cell Lymphoma ◽  
Positron Emission ◽  
History Of ◽  
Large Cell Lymphoma ◽  
Management Recommendations

Abstract Objectives To describe three further cases of anaplastic large cell lymphoma (ALCL) occurring in patients with preexisting chronic lymphocytic leukemia (CLL). We also reviewed the literature of previously published cases. Methods We discuss the clinical features, histopathology, and outcomes for three patients with ALCL and CLL from Perth, Australia. The cases were also included in a literature review of existing cases and comparisons were made with our cohort. Results The three patients included two men (aged 77 and 74 years) and one woman (aged 66 years). All had a history of untreated CLL with diagnosis established 4 to 16 years before. They had lymphadenopathy and/or cutaneous/soft tissue lesions that proved to be ALCL, ALK+ (one case) or ALCL, ALK– (two cases). Conclusions Further research is required in this area to establish prognostic and management recommendations. Increasing numbers of cases are being described. Positron emission tomography with computed tomography was not useful in our cohort for diagnosing progression.

scholarly journals Chronic Lymphocytic Leukemia as an Unusual Cause of Rapid Airway Compromise

2017 ◽  
Vol 2017 ◽  
pp. 1-4
Author(s):  
Adrian R. Bersabe ◽  
Joshua T. Romain ◽  
Erin E. Ezzell ◽  
John S. Renshaw
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Airway Obstruction ◽  
Head And Neck ◽  
Cervical Lymphadenopathy ◽  
Upper Airway ◽  
Lymphocytic Leukemia ◽  
Upper Airway Obstruction ◽  
Airway Compromise ◽  
History Of ◽  
Prevalent Form

Chronic Lymphocytic Leukemia (CLL) is the most prevalent form of non-Hodgkin’s lymphoma (NHL) in Western countries predominantly affecting adults over the age of 65. CLL is commonly indolent in nature but can present locally and aggressively at extranodal sites. Although CLL may commonly present with cervical lymphadenopathy, manifestation in nonlymphoid regions of the head and neck is not well described. CLL causing upper airway obstruction is even more uncommon. We describe a case of a patient with known history of CLL and stable lymphocytosis that developed an enlarging lymphoid base of tongue (BOT) mass resulting in rapid airway compromise.

scholarly journals Metastatic Renal Cell Carcinoma to the Parotid Gland in the Setting of Chronic Lymphocytic Leukemia

2012 ◽  
Vol 2012 ◽  
pp. 1-3 ◽  
Author(s):  
Robert Deeb ◽  
Ziying Zhang ◽  
Tamer Ghanem
Keyword(s):  
Renal Cell Carcinoma ◽  
Chronic Lymphocytic Leukemia ◽  
Parotid Gland ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Metastatic Potential ◽  
Lymphocytic Leukemia ◽  
History Of ◽  
Total Parotidectomy

Renal cell carcinoma (RCC) is infamous for its unpredictable behavior and metastatic potential. We report a case of a patient with a complex history of multifocal renal cell carcinoma and chronic lymphocytic leukemia (CLL), who subsequently developed a parotid mass. Total parotidectomy revealed this mass to be an additional site of metastasis which had developed 19 years after his initial diagnosis of RCC.

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