scholarly journals Pomalidomide desensitization in a patient hypersensitive to immunomodulating agents

2017 ◽  
Vol 24 (4) ◽  
pp. 328 ◽  
Author(s):  
J.T Seki ◽  
N. Sakurai ◽  
W. Lam ◽  
D.E. Reece
Keyword(s):  
Immunoglobulin E ◽  
Proteasome Inhibitors ◽  
Preventive Measure ◽  
Cross Reactivity ◽  
Smooth Transition ◽  
Cutaneous Toxicity ◽  
Generation Agent ◽  
Number Of Patients ◽  
Life Threatening ◽  
Grade 3

Despite progressive treatments with tandem stem-cell transplantation, patients with incurable myeloma eventually succumb to relapsed or refractory disease if left untreated. Promising agents such as proteasome inhibitors and immunomodulating imide drugs (imids), including the newer-generation agent pomalidomide, in combination with lower-dose dexamethasone, have been shown to be effective and to significantly improve and prolong survival in pretreated patients.Although the incidence of pomalidomide hypersensitivity reaction (hsr) in this class of drugs is not as well known, we have documented cutaneous toxicity (grade 3 by the Common Terminology Criteria for Adverse Events, version 4) in 2 separate cases (not yet published). Because the imids are chemically, structurally, and pharmacologically similar, it is not unreasonable to consider possible cross-reactivity in pomalidomide recipients who developed hsr when receiving previous lines of imids. As a patient’s advocate, it is only prudent to provide a responsible, and yet practical, means to better address cross-sensitivity for patients.Intervention with the use of a rapid desensitization program (rdp) as a preventive measure should be introduced before initiating pomalidomide. Such a proactive measure for the patient’s safety will ensure a smooth transition into pomalidomide treatment. A hsr can be either related or non-related to immunoglobulin E. As imids become an essential treatment backbone for myeloma and other plasma-cell diseases, an increasing number of patients could experience skin and other life-threatening toxicities, resulting in unnecessary discontinuation of these life-prolonging agents. An extemporaneously prepared pomalidomide suspension developed at our centre enables patients to undergo rdp safely. Patients enjoy a good quality of life and clinical response after the rdp procedure.

scholarly journals High-affinity allergen-specific human antibodies cloned from single IgE B cell transcriptomes

Science ◽  
2018 ◽  
Vol 362 (6420) ◽  
pp. 1306-1309 ◽  
Author(s):  
Derek Croote ◽  
Spyros Darmanis ◽  
Kari C. Nadeau ◽  
Stephen R. Quake
Keyword(s):  
B Cell ◽  
Immunoglobulin E ◽  
Variable Region ◽  
Cross Reactivity ◽  
Food Allergies ◽  
Ige Antibodies ◽  
High Affinity ◽  
Helminth Infections ◽  
Life Threatening ◽  
Antibody Class

Immunoglobulin E (IgE) antibodies protect against helminth infections but can also cause life-threatening allergic reactions. Despite their role in human health, the cells that produce these antibodies are rarely observed and remain enigmatic. We isolated single IgE B cells from individuals with food allergies and used single-cell RNA sequencing to elucidate the gene expression and splicing patterns unique to these cells. We identified a surprising example of convergent evolution in which IgE antibodies underwent identical gene rearrangements in unrelated individuals. Through the acquisition of variable region mutations, these IgE antibodies gained high affinity and unexpected cross-reactivity to the clinically important peanut allergens Ara h 2 and Ara h 3. These findings provide insight into IgE B cell transcriptomics and enable biochemical dissection of this antibody class.

scholarly journals Intensity of hemorrhage following tonsillectomy

2012 ◽  
Vol 69 (6) ◽  
pp. 500-503 ◽  
Author(s):  
Dusanka Milosevic
Keyword(s):  
Blood Transfusion ◽  
Bleeding Event ◽  
Standard Technique ◽  
Grade Classification ◽  
Number Of Patients ◽  
Life Threatening ◽  
Grade 3 ◽  
Cold Dissection ◽  
Endotracheal Anesthesia

Background/Aim. Although post-tonsillectomy hemorrhage is one of the most frequent and potentially life-threatening complications, there is no generally accepted classification of post-operative bleeding intensity. The aim of this study was to evaluate the intensity of post-tonsillectomy hemorrhage according to the five-grade classification. Methods. A total of 408 consecutive patients, aged 2 to 54 years, undergoing elective tonsillectomy, with (n=261) or without (n=147) adenoidectomy, were included in this prospective study. Tonsillectomy was performed under general anesthesia using standard technique of cold dissection with a snare. Any bleeding event was recorded. The severity of post-operative hemorrhage was classified in five grades. Results. In 11 (2.70%) of the patients grade 1 hemorrhage following tonsillectomy occurred, 4 (0.98%) had grade 2 and 2 (0.49%) of the patients had grade 3 post-operative bleeding. Grades 4 and 5 were not recorded, and no patient received a blood transfusion. Conclusion. Post-tonsillectomy hemorrhage can be expected in a small number of patients undergoing tonsillectomy. Hemorrhage is mostly primary and rarely requires treatment under endotracheal anesthesia and blood transfusion.

Institutional experiences with panitumumab monotherapy in metastatic colorectal cancer (mCRC) patients (pts) intolerant to cetuximab

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 14579-14579 ◽  
Author(s):  
A. D. Langerak ◽  
E. Mitchell ◽  
P. Cheema ◽  
G. L. River ◽  
M. Shing
Keyword(s):  
Additional Data ◽  
Growth Factor Receptor ◽  
Cross Reactivity ◽  
Compassionate Use ◽  
Pain Anxiety ◽  
Intravenous Saline ◽  
Life Threatening ◽  
Infusion Reactions ◽  
Epidermal Growth ◽  
Grade 3

14579 Background: Two monoclonal antibodies (mAbs) targeting the epidermal growth factor receptor are approved for the treatment (tx) of advanced mCRC - panitumumab (Vectibix™), a fully human mAb, and cetuximab (Erbitux®), a chimeric mAb. Potential for cross-reactivity between these two mAbs with regard to infusion reactions (IR) has not been fully explored. Given the lack of sequence homology between the 2 agents and the fully human nature of panitumumab, it is hypothesized that pts intolerant to cetuximab due to IR could be tolerant to panitumumab. Methods: Single pt tx IND applications to administer panitumumab monotherapy in pts with advanced mCRC were approved by the FDA and local institutions as part of the Panitumumab Compassionate Use program. Eligibility also included previous tx with standard chemotherapy and intolerability to cetuximab, ie. CTCAE v3.0 grade 3 (severe) or grade 4 (life-threatening) IR. Results: Upon informed consent, 4 pts (2M/ 2F) were enrolled in 4 centers. Median (range) age was 62.5 (52, 64) years. 3 pts had colon cancer and 1 pt had rectal cancer. All had surgery and received prior 5-fluorouracil, leucovorin, irinotecan, oxaliplatin, bevacizumab, and cetuximab. One pt had a CTC grade 3 IR and 3 pts had a CTC grade 4 IR to cetuximab. IR symptoms included fever, wheezing, dyspnea, chest/back/abdominal pain, anxiety, hypotension, flushing, tachycardia, and tachypnea. Two IRs occurred within 10 minutes of the first cetuximab infusion. Cetuximab was discontinued and IR symptoms were treated with bronchodilators, diphenhydramine, epinephrine, methylprednisolone, oxygen, intravenous saline, and hospitalization. All pts received panitumumab. Data for pts 1, 2, and 3 are available: pt 1 received 1 infusion of panitumumab at 5 mg/kg Q2W with premedication (diphenhydramine and methylprednisolone); pts 2 and 3 received 7 and 2 panitumumab infusions, respectively, at 6 mg/kg Q2W without premedication. No pt had an IR to panitumumab. Pt 2 had stable disease; pts 1 and 3 died due to disease progression. Conclusions: Panitumumab monotherapy was tolerated without incidence of an IR in these cases of mCRC pts who are intolerant to cetuximab due to a severe or life-threatening IR. Additional data will be presented. No significant financial relationships to disclose.

Ion Channel Remodelling in Atrial Fibrillation

2011 ◽  
Vol 7 (2) ◽  
pp. 97 ◽  
Author(s):  
Niels Voigt ◽  
Dobromir Dobrev ◽  
◽  
Keyword(s):  
Atrial Fibrillation ◽  
Ion Channel ◽  
Antiarrhythmic Drugs ◽  
Current Knowledge ◽  
Bleeding Complications ◽  
Large Size ◽  
Cardiovascular Morbidity And Mortality ◽  
Number Of Patients ◽  
Life Threatening ◽  
Underlying Mechanisms

Atrial fibrillation (AF) is the most common arrhythmia and is associated with substantial cardiovascular morbidity and mortality, with stroke being the most critical complication. Present drugs used for the therapy of AF (antiarrhythmics and anticoagulants) have major limitations, including incomplete efficacy, risks of life-threatening proarrhythmic events and bleeding complications. Non-pharmacological ablation procedures are efficient and apparently safe, but the very large size of the patient population allows ablation treatment of only a small number of patients. These limitations largely result from limited knowledge about the underlying mechanisms of AF and there is a hope that a better understanding of the molecular basis of AF may lead to the discovery of safer and more effective therapeutic targets. This article reviews the current knowledge about AF-related ion-channel remodelling and discusses how these alterations might affect the efficacy of antiarrhythmic drugs.

Safety of Vinflunine in Patients with Advanced Urothelial Carcinoma Refractory to Platinum-based Chemotherapy: A Prospective Pilot Study

2019 ◽  
Vol 14 (1) ◽  
pp. 31-36
Author(s):  
Raafat Abdel-Malek ◽  
Kyrillus S. Shohdy ◽  
Noha Abbas ◽  
Mohamed Ismail ◽  
Emad Hamada ◽  
...  
Keyword(s):  
Pilot Study ◽  
Adverse Events ◽  
Urothelial Carcinoma ◽  
Transitional Cell ◽  
Chemotherapeutic Agents ◽  
Serious Adverse Events ◽  
Platinum Based Chemotherapy ◽  
Number Of Patients ◽  
Advanced Urothelial Carcinoma ◽  
Grade 3

Background: Several single chemotherapeutic agents have been evaluated as the second-line treatment of advanced urothelial carcinoma. Despite encouraging efficacy outcomes, toxicity has often led to dose modifications or discontinuation. We aimed to assess the safety of vinflunine in a particular population of advanced transitional cell carcinoma of urothelium (TCCU), that were exposed to the previous toxicity of chemotherapy. Methods: This is an open-label, prospective, single-center pilot study to evaluate the response rate and safety profile of vinflunine in patients with advanced TCCU. It was planned to enroll 25 evaluable patients. Eligible patients are those with progressive disease after first-line platinum-based regimen for advanced or metastatic disease. Results: The study was prematurely closed due to two sudden deaths that were judged by the review board as treatment-related. Only ten patients were evaluated and received at least one cycle of vinflunine. All but one were male and seven underwent radical surgery. Eight had a distant metastasis (mainly lung and/or liver). Disease control rate was 40%, four patients had a partial response with median duration of response of 3.5 months. The median overall survival was 3.2 months (95% CI:1.67- 4.73). There were three serious adverse events namely two sudden deaths and one grade 4 thrombocytopenia. Nine grade 3/4 adverse events occurred. The most common all-grade adverse events were fatigue (50%), constipation (40%) and vomiting (40%). Moreover, grade 3 fatigue occurred in 30% of patients. Only one patient, who achieved PR for 5 months, was fit to receive further cytotoxic chemotherapy. Conclusion: The activity of vinflunine in advanced urothelial carcinoma came at the expense of its safety. The use of vinflunine has to be limited to the selected group of patients. However, this is a single institute experience in a limited number of patients.

scholarly journals Autoimmune Responses in Oncology: Causes and Significance

2021 ◽  
Vol 22 (15) ◽  
pp. 8030
Author(s):  
Halin Bareke ◽  
Pablo Juanes-Velasco ◽  
Alicia Landeira-Viñuela ◽  
Angela-Patricia Hernandez ◽  
Juan Jesús Cruz ◽  
...  
Keyword(s):  
Cancer Immunotherapy ◽  
Protein Microarrays ◽  
Cross Reactivity ◽  
Fine Tuning ◽  
Cancer Treatments ◽  
Aberrant Expression ◽  
Specificity And Sensitivity ◽  
Anti Cancer ◽  
Life Threatening ◽  
Considerable Impact

Specific anti-tumor immune responses have proven to be pivotal in shaping tumorigenesis and tumor progression in solid cancers. These responses can also be of an autoimmune nature, and autoantibodies can sometimes be present even before the onset of clinically overt disease. Autoantibodies can be generated due to mutated gene products, aberrant expression and post-transcriptional modification of proteins, a pro-immunogenic milieu, anti-cancer treatments, cross-reactivity of tumor-specific lymphocytes, epitope spreading, and microbiota-related and genetic factors. Understanding these responses has implications for both basic and clinical immunology. Autoantibodies in solid cancers can be used for early detection of cancer as well as for biomarkers of prognosis and treatment response. High-throughput techniques such as protein microarrays make parallel detection of multiple autoantibodies for increased specificity and sensitivity feasible, affordable, and quick. Cancer immunotherapy has revolutionized cancer treatments and has made a considerable impact on reducing cancer-associated morbidity and mortality. However, immunotherapeutic interventions such as immune checkpoint inhibition can induce immune-related toxicities, which can even be life-threatening. Uncovering the reasons for treatment-induced autoimmunity can lead to fine-tuning of cancer immunotherapy approaches to evade toxic events while inducing an effective anti-tumor immune response.

Cancer and COVID-19: A proposed mechanism with therapeutic interventions.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3135-3135
Author(s):  
Yan Leyfman ◽  
Nancy Emmanuel ◽  
Aleksey Tentler ◽  
Jared Cappelli ◽  
Timothy K Erick ◽  
...  
Keyword(s):  
Respiratory Illness ◽  
Organ Damage ◽  
Multiple Organ ◽  
Therapeutic Interventions ◽  
Actual Number ◽  
Data Registry ◽  
Number Of Patients ◽  
Increased Risk ◽  
Life Threatening ◽  
Active Cancer

3135 Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel betacoronavirus that causes the respiratory illness coronavirus disease 2019 (COVID-19). COVID-19 ranges in severity from an asymptomatic viral infection to life-threatening cases of pneumonia, acute respiratory distress syndrome (ARDS), multi-organ damage and sepsis. Cancer patients are at an increased risk of severe SARS-CoV-2 infection due to their immunocompromised status. We propose a mechanism by which SARS-CoV-2 infection causes multiple organ damage through IL-6-mediated inflammation and hypoxia-induced cellular metabolic alterations leading to cell death. Hypoxia is also induced by malignancy due to alterations in metabolism, resulting in greater IL-6 secretion. Methods: To highlight the possible effect of active cancer on the likelihood of hypoxia in COVID-19, we analyzed the correlation between cancer status and the severity of COVID-19 from the COVID-19 and Cancer Consortium data registry. For cancer status, we looked at progressive cancer and remission of cancer only -- those being the two extremes of presence and absence of uncontrolled cancer. Similar to prior studies, the severity of COVID-19 was used as an indication of hypoxia. Results: We observed a 24% positive deviation between expected and actual number of patients with actively progressing cancer who had hypoxic COVID-19 (moderate to severe), and a 26.9% negative deviation between expected and actual number of patients with active cancer who had no hypoxia with COVID-19 (p<0.0001). Conversely, for patients with cancer in remission, there was only a +5.8% and -5.1% deviation between expected and actual number of patients who did not have hypoxia and who had hypoxia, respectively. Conclusions: These results suggest that in the presence of poorly controlled malignancy, there is an increased likelihood of hypoxia in patients with COVID-19, thereby exacerbating downstream cytokine release syndrome and contributing to prolonged systemic inflammatory injury. Appreciating this pathway, future therapies can be developed to target the pathogenesis of both diseases and prevent progression, as seen with mesenchymal stem cells, which demonstrated a 91% overall survival and 100% survival in patients younger than 85 years old at one month after a single treatment.[Table: see text]

Angioedema and Maculopapular Eruptions Associated with Carbamazepine Administration

CNS Spectrums ◽  
2006 ◽  
Vol 11 (5) ◽  
pp. 352-354 ◽  
Author(s):  
Alby Elias ◽  
Subramoniam Madhusoodanan ◽  
David Pudukkadan ◽  
James T. Antony
Keyword(s):  
Mood Disorders ◽  
Side Effect ◽  
Immunoglobulin E ◽  
Maculopapular Rash ◽  
Vascular Leakage ◽  
Diagnosis And Treatment ◽  
Indian Woman ◽  
The Third ◽  
Rare Side Effect ◽  
Life Threatening

ABSTRACTCutaneous rashes and eruptions can be caused by many medications, including carbamazepine. The presentation can be varied depending on severity. Cutaneous eruptions occur in 3% of individuals administered carbamazepine. Angioedema, a rare side effect of carbamazepine, involves vascular leakage in dermis and subcutis mediated by immunoglobulin E and/or bradykinins. Angioedema is more common in females and in the third decade of life. We report the case of a 27-year-old Indian woman who developed maculopapular rash and angioedema secondary to carbamazepine administration. The patient responded successfully to withdrawal of the drug and treatment with antihistamines. Due to the potentially life-threatening complications of this condition and the increasing use of anticonvulsants in the treatment of mood disorders, psychiatrists must be aware of the diagnosis and treatment of this condition.

Evaluation of Orphan Products by the U.S. Food and Drug Administration

1992 ◽  
Vol 8 (4) ◽  
pp. 647-657 ◽  
Author(s):  
Marlene E. Haffner ◽  
John V. Kelsey
Keyword(s):  
Drug Administration ◽  
Rare Diseases ◽  
Food And Drug Administration ◽  
Orphan Drugs ◽  
Marketing Approval ◽  
Drug Products ◽  
Governmental Agencies ◽  
Number Of Patients ◽  
Life Threatening ◽  
The U.S

AbstractOrphan drug products generally are used in treating or preventing rare diseases. The small number of patients available for study may create special problems in the evaluation of these products. This paper examines some of the special problems that are associated with the design and implementation of studies to evaluate the safety and efficacy of orphan drugs. The U.S. Food and Drug Administration (FDA) has not established special criteria for evaluating orphan drugs per se, but the FDA has been flexible in evaluating drug products that present special problems, especially when these products are for treatment of serious of life-threatening illnesses. The FDA and other U.S. governmental agencies also have taken steps to promote the development and availability of drugs for rare diseases, including making these products available to patients who are in need, even before the drugs have full FDA marketing approval.

scholarly journals Diagnostic difficulties and features of endovideosurgical treatment of a patient with mucocele of the appendix

2020 ◽  
Vol 12 (2) ◽  
pp. 85-90
Author(s):  
Badri V. Sigua ◽  
Vyacheslav P. Zemlyanoy ◽  
Elguja L. Lataria ◽  
Alexey A. Kurkov ◽  
Vyacheslav A. Melnikov ◽  
...  
Keyword(s):  
Benign Tumor ◽  
Abdominal Cavity ◽  
Clinical Manifestations ◽  
Vermiform Appendix ◽  
Diagnostic Methods ◽  
Number Of Patients ◽  
Mucocele Of The Appendix ◽  
Diagnostic Difficulties ◽  
Life Threatening ◽  
The Right

The mucocele of the appendix is the expansion of the appendix with the accumulation of a large amount of mucus. The mechanism and causes of mucocele are not fully understood. According to some authors, such changes in the appendix can occur due to cicatricial narrowing of the lumen of the appendix, compression or blockage of its base. Other authors believe that the mucocele of the appendix is a benign tumor that develops from the remnants of primitive mesenchyme and is sometimes prone to malignancy. Clinical manifestations of mucocele of the appendix are nonspecific. In a number of patients, this disease causes pain in the right abdomen, more often pulling, intermittent. However, the disease is often asymptomatic. In this regard, diagnosis is established only during performing an operation, most often, regarding acute appendicitis. Nevertheless, instrumental diagnostic methods such as ultrasound and computed tomography of the abdominal and pelvic organs make it possible to suspect mucocele. Despite the frequent asymptomatic, non-aggressive course, a number of life-threatening complications can become the outcome of the mucocele of the vermiform appendix. The most formidable complication is the rupture of the appendix with mucus entering free abdominal cavity, followed by the development of peritoneal pseudomyxoma due to implantation of mucus-forming cells. The only option for radical treatment of the mucocele of the appendix is a surgical intervention. A presented clinical case demonstrates the difficulties of diagnosis, as well as the features of surgical treatment of a patient with a mucocele of the appendix.

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