Journal articles on the topic 'Asthma – Chemotherapy'
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FALLIERS, C. "Cancer chemotherapy: Hormonal changes and recurring asthma." Journal of Allergy and Clinical Immunology 87, no. 3 (March 1991): 747–48. http://dx.doi.org/10.1016/0091-6749(91)90398-8.
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Palmieri, C., R. Gillmore, A. Menzies-Gow, S. Fishpool, D. Robinson, R. Shaw, and R. C. Coombes. "Resolution of late-onset asthma following high-dose chemotherapy." Bone Marrow Transplantation 32, no. 8 (October 2003): 847–48. http://dx.doi.org/10.1038/sj.bmt.1704268.
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Anak, Sema, Nermin Guler, and Ebru Tugrul Saribeyoglu. "POSSIBLE CURATIVE EFFECT OF INTENSIVE CHEMOTHERAPY ON ASTHMA IN CHILDREN." Pediatric Hematology and Oncology 18, no. 6 (January 2001): 421–22. http://dx.doi.org/10.1080/088800101316922065.
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Protasov, A. D., M. P. Kostinov, A. V. Zhestkov, D. O. Gorbachev, A. M. Kostinov, M. E. Elner, and T. A. Kozina. "Changes in Sputum Microbiocenosis and Clinical Pattern Under Different Vaccination Protocols for Pneumococcal Infection in Patients with Bronchial Asthma." Global Journal of Respiratory Care 8 (December 28, 2022): 18–27. http://dx.doi.org/10.12974/2312-5470.2022.08.05.
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Bronchial asthma is a serious public health issue. It is important to reduce the frequency of attacks for BA patients. Vaccination for pneumococcal infection is an important complementary tool that can improve the clinical pattern of bronchial asthma. The study involved 102 patients with bronchial asthma, who were monitored over 4 years. The patients were divided into 4 groups based on the vaccination scheme used for pneumococcal infection: PCV13, PPV23, PPV23/PCV13, PCV13/PPV23. Sequential vaccination with pneumococcal conjugate and polysaccharide vaccines leads to a decrease in the isolation of pneumococcus from sputum in BA patients, which has a pronounced positive effect on the clinical pattern of this disease, namely, it leads to a decrease in the frequency of attacks, the requirement for courses of antibacterial chemotherapy and hospitalizations, and therefore this vaccination protocol should be included in the standards of BA patient management.
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Jones, PD, RL Henry, L. Francis, and PG Gibson. "Chemotherapy reduces the prevalence of asthma symptoms in children with cancer: Implications for the role of airway inflammation in asthma." Journal of Paediatrics and Child Health 35, no. 3 (June 1999): 269–71. http://dx.doi.org/10.1046/j.1440-1754.1999.00358.x.
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Falliers, Constantine J. "Relapse and Repeated Remission of Asthma After Cancer Chemotherapy and Secondary Hormonal Changes." Journal of Asthma 28, no. 5 (January 1991): 381–87. http://dx.doi.org/10.3109/02770909109089465.
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Walters, E. Haydn, Julia AE Walters, and Richard Wood-Baker. "Anti-IgE and chemotherapy: a critical appraisal of treatment options for severe asthma." Expert Opinion on Pharmacotherapy 8, no. 5 (March 22, 2007): 585–92. http://dx.doi.org/10.1517/14656566.8.5.585.
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Tintinger, Gregory R., Charles Feldman, Annette J. Theron, and Ronald Anderson. "Montelukast: More than a Cysteinyl Leukotriene Receptor Antagonist?" Scientific World JOURNAL 10 (2010): 2403–13. http://dx.doi.org/10.1100/tsw.2010.229.
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The prototype cysteinyl leukotriene receptor antagonist, montelukast, is generally considered to have a niche application in the therapy of exercise- and aspirin-induced asthma. It is also used as add-on therapy in patients whose asthma is poorly controlled with inhaled corticosteroid monotherapy, or with the combination of a long-acting β(2)-agonist and an inhaled corticosteroid. Recently, however, montelukast has been reported to possess secondary anti-inflammatory properties, apparently unrelated to conventional antagonism of cysteinyl leukotriene receptors. These novel activities enable montelukast to target eosinophils, monocytes, and, in particular, the corticosteroid-insensitive neutrophil, suggesting that this agent may have a broader spectrum of anti-inflammatory activities than originally thought. If so, montelukast is potentially useful in the chemotherapy of intermittent asthma, chronic obstructive pulmonary disease, cystic fibrosis, and viral bronchiolitis, which, to a large extent, involve airway epithelial cell/neutrophil interactions. The primary objective of this mini-review is to present evidence for the cysteinyl leukotrien–independent mechanisms of action of montelukast and their potential clinical relevance.
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Bitik, B., M. Aydin, G. Sahin Dalgic, D. Kaskari, and A. E. Yucel. "AB0464 THE ROLE OF CYCLOPHOSPHAMIDE CHEMOTHERAPY IN THE TREATMENT OF EOSINOPHILIC GRANULOMATOSIS WITH POLYANGIITIS." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 1530.2–1531. http://dx.doi.org/10.1136/annrheumdis-2020-eular.6481.
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Background:Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare type of ANCA associated Vasculitis (AAVs). Cyclophosphamide (CYC) is generally recommended for the induction of remission in life/organ threatening AAVs in combination with glucocorticoids. However, due to its rarity, randomized controlled trials regarding the efficacy of treatment modalities in EGPA are hard to perform. Therefore, the level of evidence for the use of CYC in the treatment of EGPA is lower when compared to other AAVs (1).Objectives:The aim of this study is to investigate common therapeutic agents used for the treatment of patients with EGPA.Methods:Medical records of patients who were followed-up with the diagnosis of EGPA between 2007-2020, in rheumatology clinics of Ankara and Adana Hospitals of Başkent University, were analyzed retrospectively. Treatment outcomes were assessed.Results:Records of 11 patients (six females) were analyzed. The median age was 47 (19-77) years. The median follow-up time of the patients was 24 (9-156) months. Six patients were diagnosed with asthma. The median time between the diagnosis of asthma and EGPA was 4.5 (1-3) years. Five patients had tissue biopsies. Biopsy locations were terminal ileum, lung, myocardium and nerve. The most common forms of involvement were asthma, eosinophilic pneumonia and / or nodule, cardiovascular involvement, mononoritis multiplex, vasculitic skin rash, arthritis and bowel involvement, respectively. P-ANCA was positive in 8 patients. Three patients had myocarditis and cardiomyopathy, and two patients had isolated valve problems. The median BVAS value at the time of diagnosis and the third month of treatment was 17 (6-27) and 4 (2-7), respectively.Nine patients used oral 1mg/ kg methylprednisolone (MP) and 500mg CYC every two weeks as an induction therapy. The cumulative median CYC dose was 4.5 g (1.5-8). Neither of the patients developed CYC related side effects. MP was tapered to 2 mg in five patients, and was quited in two patients. Azathioprine (AZA) was used in remission treatment following CYC therapy. Rituximab (RTX) therapy 1 g twice, 2 weeks apart was initiated in two patients due to unresponsiveness to CYC. While RTX was effective in one patient, newly developed renal involvement was detected after the third cycle of RTX therapy in other patient. Two patients had pregnancy plan therefore they used AZA plus MP as induction. A patient had mycophenolate mofetil plus MP due to AZA allergy. All patients are currently in remission except one patient.Conclusion:In seven out of 11 EGPA patients, long-term remission was achieved with CYC treatment. CYC appears to be an effective and inexpensive method of first-line treatment for organ threatening EGPA.References:[1]Yates M, Watts RA, Bajema IM, et al. EULAR/ERA-EDTA recommendations for the management of ANCA-associated vasculitis. Ann Rheum Dis. 2016 Sep;75(9):1583-94.Disclosure of Interests:None declared
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Zhu, Xiaorui. "Clinical Effect of Auricular Point Sticking in Patients with Lung Cancer Receiving Chemotherapy." Proceedings of Anticancer Research 5, no. 6 (November 30, 2021): 73–77. http://dx.doi.org/10.26689/par.v5i6.2810.
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Objective: To discuss and analyze the clinical effect of auricular point sticking in lung cancer chemotherapy. Methods: Sixty-two patients with lung cancer treated with chemotherapy in Suqian Traditional Chinese Medicine Hospital of Jiangxi Province were selected for case evaluation and analysis. The time span of the research was from June 2020 to June 2021. The patients were divided into two groups: a study group (n = 31) and a control group (n = 31) based on their medical record numbers. All the patients were treated with conventional western medicine before and after chemotherapy to prevent adverse reactions; however, the patients in the study group were also treated with auricular point sticking in addition to the former. The relevant indexes of the two groups were compared. Results: The incidence of adverse reactions was significantly lower in the study group compared to the control group (P < 0.05); the rate of symptomatic relief of the patients in the study group was higher than that of the control group (P < 0.05); the stress response indexes toward chemotherapy of the study group were better than those of the control group (P < 0.05). Conclusion: Auricular point sticking for patients with lung cancer who are receiving chemotherapy can reduce the incidence of adverse reactions, alleviate clinical symptoms, such as chest distress, asthma, and poor appetite, significantly alleviate stress response caused by chemotherapy, as well as promote the treatment effect; thus, it is worthy of promotion.
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Jones, Peter D., Richard L. Henry, Peter G. Gibson, Robyn Hankin, and Kellie Carty. "Chemotherapy for malignancy induces a remission in asthma symptoms and airway inflammation but not airway hyperresponsiveness." Pediatric Pulmonology 26, no. 1 (July 1998): 74–77. http://dx.doi.org/10.1002/(sici)1099-0496(199807)26:1<74::aid-ppul11>3.0.co;2-5.
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Cathcart-Rake, Elizabeth Jane, David Zahrieh, Deanne s. Smith, Susan Young, Eric G. Wolfe, Amanda O'Connor, Stephan Thome, et al. "Nasal vestibulitis: An MNCCTN natural history trial—Nasal vestibulitis symptoms associated with paclitaxel, docetaxel, and other chemotherapy agents." Journal of Clinical Oncology 38, no. 15_suppl (May 20, 2020): e24086-e24086. http://dx.doi.org/10.1200/jco.2020.38.15_suppl.e24086.
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e24086 Background: Nasal vestibulitis has been infrequently described as a side effect of cancer-directed therapy; however, a preliminary study reported that 71% of patients undergoing taxane chemotherapy experienced nasal vestibulitis symptoms. This natural history trial describes the incidence, characteristics, and severity of nasal vestibulitis symptoms among patients undergoing paclitaxel, docetaxel, and non-taxane chemotherapy. Methods: Eligible participants who reported baseline (prior to starting chemotherapy) nasal symptoms ≤ 2 on a 10-point scale were enrolled in this trial upon initiation of a new treatment regimen, involving paclitaxel or docetaxel, or non-taxane chemotherapy. Participants completed nasal symptom logs each time they received a dose of therapy until either the regimen was stopped or four months had passed. The proportion of patients reporting new nasal symptoms was estimated within each cohort with the 95% exact confidence interval (CI). A cumulative incidence model was utilized to quantify the incidence of treatment-emergent nasal symptoms within each cohort, while controlling for age, sex, smoking history, and history of asthma or allergies. Results: Thirty-five participants received paclitaxel, 21 received docetaxel, and 25 received other types of chemotherapy. 86.4% of participants were female, mean age was 60.2 ± 11.2 years; 93.8% of participants completed 2 or more surveys. A higher percentage of participants in the paclitaxel cohort experienced new nasal vestibulitis symptoms than participants in the other two cohorts. The percentage (95% CI) of participants with nasal symptoms, for patients receiving paclitaxel, docetaxel, and non-taxane chemotherapy were 74.3% (56.7%, 87.5%), 47.6% (25.7%, 70.2%), and 44.0% (24.4%, 65.1%), respectively. Epistaxis was reported by 60% of participants in the paclitaxel cohort. Paclitaxel-receiving participants also reported nasal dryness (48.6%), scabbing (40.0%), and pain (20.0%). Nearly half of participants reported moderate symptoms (4-7 out of a 10-point scale), with 8.6% reporting symptoms as severe (8-10 on a 10-point scale). Conclusions: Nasal vestibulitis is a common side effect of chemotherapy, especially paclitaxel chemotherapy.
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Ou, Judy, Heidi Hanson, Joemy Ramsay, Claire Leiser, Yue Zhang, James VanDerslice, C. Pope, and Anne Kirchhoff. "Fine Particulate Matter and Respiratory Healthcare Encounters among Survivors of Childhood Cancers." International Journal of Environmental Research and Public Health 16, no. 6 (March 26, 2019): 1081. http://dx.doi.org/10.3390/ijerph16061081.
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Some chemotherapies that treat childhood cancers have pulmonary-toxic properties that increase risk for adverse respiratory-health outcomes. PM2.5 causes similar outcomes but its effect among pulmonary compromised cancer survivors is unknown. This case-crossover study identified the PM2.5-associated odds for primary-respiratory hospitalizations and emergency department visits among childhood cancer survivors in Utah. We compared risk among chemotherapy-treated survivors to a cancer-free sample. We calculated 3-day-average PM2.5 by ZIP code and county for event and control days. Conditional logistic regression estimated odds ratios. Models were stratified by cause of admission (infection, respiratory disease, asthma), previous chemotherapy, National Ambient Air Quality Standard (NAAQS), and other variables. Results are presented per 10 µg/m3 of PM2.5. 90% of events occurred at 3-day PM2.5 averages <35.4 µg/m3, the NAAQS 24-h standard. For survivors, PM2.5 was associated with respiratory hospitalizations (OR = 1.84, 95% CI = 1.13–3.00) and hospitalizations from respiratory infection (OR = 2.09, 95% CI = 1.06–4.14). Among chemotherapy-treated survivors, the PM2.5-associated odds of respiratory hospitalization (OR = 2.03, 95% CI = 1.14–3.61) were significantly higher than the cancer-free sample (OR = 0.84, 95% CI = 0.57–1.25). This is the first study to report significant associations between PM2.5 and respiratory healthcare encounters in childhood cancer survivors. Chemotherapy-treated survivors displayed the highest odds of hospitalization due to PM2.5 exposure and their risk is significantly higher than a cancer-free sample.
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Escalante, C. P., J. H. Oh, D. D. Baum, M. Mante, A. Zalpour, S. Spivey, C. Stewart, J. Ensor, T. Grover, and R. Freedman. "Immediate adverse reactions to chemotherapy: Experience of a large ambulatory treatment center." Journal of Clinical Oncology 24, no. 18_suppl (June 20, 2006): 8558. http://dx.doi.org/10.1200/jco.2006.24.18_suppl.8558.
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8558 Background: In recent years there has been a proliferation of Ambulatory Chemotherapy Treatment Centers (ATC). The incidence of hypersensitivity and other immediate adverse drug reactions (IADR) in these ATC units have not been well studied. We aim to describe our experience with IADR in our ATC. Methods: Retrospective chart review was conducted for all patients in the Adverse Drug Reaction Report database (Maxsys II) for the year 2004. Data was abstracted for demographics, risk factors, clinical characteristics, and outcomes of IADR. Overall frequency of different chemotherapeutic and monoclonal agents infused was obtained for the same period through the pharmacy database. Results: In 2004, 81,580 chemotherapy infusions were given and 256 IADR (0.31%) were reported. The mean age was 55 years and 45% were males. The most common drugs used were fluorouracil (12.9%), paclitaxel (9.4%), docetaxel (6.1%), carboplatin (5.9%), and gemcitabine (5.8%). The table shows the most prevalent agents that led to IADR. Common symptoms included flushing (52.3%), dyspnea (27.3%), chest discomfort (27%), pruritus (22.7%), and hypertension (18.4%). Diphenhydramine (85.5%), hydrocortisone (37.1%), and dexamethasone (17.2%) were the most common drugs used for treatment of IADR. Common risk factors included previous allergy to medications (43.4%), previous IADR (19.5%), previous reactions to iodide (7.8%), allergies to seafood (1.6%), allergic rhinitis (1.2%), urticaria (1.2%), and asthma (0.8%). Most patients had their chemotherapy resumed and completed (87.9%) on the same day. Discussion: IADR were rare. Most cases were easily treated and chemotherapy was restarted and completed in the same day. However, they still pose a significant burden to cancer patients. Prospective studies are needed to further evaluate the identified risk factors and most common offending agents in outpatient settings. This will help develop pathways for more effective prevention and treatment of these IADR. [Table: see text] No significant financial relationships to disclose.
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Kim, Esther, Amily Koshy, Shannon Higgins, Andrew Lassman, and Fabio Iwamoto. "COVD-20. COVID-19 INFECTION DURING CHEMOTHERAPY FOR MALIGNANT GLIOMA: OUTCOMES AMONG 3 PATIENTS." Neuro-Oncology 22, Supplement_2 (November 2020): ii25. http://dx.doi.org/10.1093/neuonc/noaa215.103.
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Abstract BACKGROUND Chemotherapy may increase risk of SARS-COV-2 infection and COVID-19 severity. METHODS A patient developed COVID-19 during chemotherapy for glioma. We retrospectively identified others diagnosed with COVID-19 during temozolomide or lomustine for glioma. RESULTS (1) A 64 year-old woman (index patient) with anaplastic oligodendroglioma received PCV 22 months previously. Baseline White Blood Cell (WBC) count was 4.2 and Absolute Neutrophil Count (ANC) was 2.7 K/uL. KPS was 90 without comorbidities. For recurrence she initiated temozolomide but developed fever on cycle 1 day 2. SARS-COV-2 PCR was positive. Further temozolomide was held. She is recovering as an outpatient. (2) A 27 year-old man with anaplastic astrocytoma received concurrent RT/temozolomide then 1 cycle of adjuvant temozolomide. Baseline WBC was 8.3, ANC 5.2, and KPS 90. Obesity, asthma, and pre-diabetes were comorbidities. Hyposmia/hypogeusia and low-grade fever began, in retrospect, during concurrent RT/temozolomide. PCR for SARS-COV-2 was negative 2 months after symptom onset; serology detected both IgG and IgM when WBC was 6.6 and ANC 4.0. Cycle 2 of adjuvant temozolomide was held until fever resolved (spontaneously); hyposmia/hypogeusia persist. (3) A 53 year-old man with glioblastoma previously received RT/temozolomide, then lomustine and bevacizumab for progression. WBC was 5.1, ANC 4.0, and KPS 60. He was obese. Fever, chills, and dyspnea developed on lomustine cycle 2 day 38. SARS-COV-2 PCR was positive. He was hospitalized and chemotherapy held; symptoms resolved 12 days after onset, but PCR continued to show detectable virus 32 days later. PCR became negative after 50 days total, and treatment resumed uneventfully. DISCUSSION All 3 patients recovered from SARS-COV-2 infection despite active temozolomide or lomustine chemotherapy. Normal ANC, high KPS, and early detection may have contributed to limited symptom severity and duration, despite obesity and other comorbidities in 2 cases. Detection changed management by delaying additional cycles of immunosuppressive chemotherapy until recovery.
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Mitsui, Takeki, Akihiko Yokohama, Hiromi Koiso, Takuma Ishizaki, Hideki Uchiumi, Takayuki Saitoh, Hiroshi Handa, et al. "Development of IgG4-related disease 10 years after chemotherapy for diffuse large B cell lymphoma and longstanding bronchial asthma." International Journal of Hematology 98, no. 1 (May 12, 2013): 122–28. http://dx.doi.org/10.1007/s12185-013-1359-z.
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Carson, Cindy Alberts. "Magnesium oxide supplements for the treatment of post-chemotherapy sleep disturbance." Journal of Clinical Oncology 35, no. 5_suppl (February 10, 2017): 175. http://dx.doi.org/10.1200/jco.2017.35.5_suppl.175.
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175 Background: While every cancer patient suffers from anxiety and sleep disturbance during cancer treatment, many physicians do not recognize that these problems can continue long after treatment has ended. Many cancer patients feel increased anxiety immediately after treatment ends when they find themselves “on their own,” without the protection of the medical armamentarium. The fear of recurrence, uncertainty about the future, a sense of vulnerability, awareness of mortality, and grief for the loss of a disease-free life all contribute to anxiety and sleep disturbance long term. Magnesium has been used for sleep induction and relaxation for centuries. The primary mechanism by which sleep is enhanced is by muscle relaxation. Magnesium induces muscle relaxation by preventing calcium from binding to troponin, parvalbumin, myosin, and calmodulin, thereby blocking muscle contraction. High levels of free magnesium competitively bind these proteins, and the slow dissociation of bound magnesium provides prolonged relaxation. It is for this reason that magnesium has a long history of use as a tocolytic in labor, as an adjunct to asthma treatment, and as a powerful laxative. Methods: 23 patients in a primary care practice reported continued anxiety and difficulty with sleep initiation following chemotherapy and/or radiation for various forms of cancer. Rather than use SSRIs, benzodiazepines, or sleep medications, all patients were started on an over the counter 1,000 mg magnesium oxide supplement, taken 1 hour before bedtime for 2 weeks. Results: Four patients dropped out before the end of the study period due to magnesium-induced diarrhea. 19 patients completed the 2-week study. Of these, 14 reported a noticeable reduction of sleep latency and an improvement in sleep quality. 11 also reported a subjective sense of reduced anxiety overall. 5 reported an improvement in nocturnal leg cramps, which had been interfering with sleep quality. Conclusions: Overall, magnesium proved to be a well-tolerated treatment for sleep disturbance and anxiety in the majority of the patients studied.
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Rahman, Bushra, Jawad Bilal, Qurat Ul Ain Riaz Sipra, and Irbaz Bin Riaz. "All That Wheezes Is Not Asthma: A Case of Diffuse Large B-Cell Lymphoma of the Larynx." Case Reports in Oncological Medicine 2017 (2017): 1–4. http://dx.doi.org/10.1155/2017/7072615.
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Localized laryngeal lymphoma is a rare entity with an incidence of less than 1% of all laryngeal neoplasms. Diffuse large B-cell lymphoma (DLBCL) is the most common type of laryngeal neoplasms. Here, we describe a case of a young 28-year-old female with large B-cell lymphoma who remained undiagnosed for a long time owing to a myriad of nonspecific presentation including “wheezing.” Although primary laryngeal lymphomas constitute a diagnostic challenge since they are rare, one should have a high index of suspicion for lymphoma of the larynx in patients presenting with unresolved wheezing as it can present catastrophically with acute airway obstruction requiring immediate surgical intervention which was observed in this case. Treatment includes radiotherapy, chemotherapy, immunotherapy, or a combination of these. We hope that the discussions ensuing from case reports regarding uncommon presentations of laryngeal lymphoma may spur the formation of regional/international databases for the description of lymphomas with unusual presentations. This effort can lead to in-depth study of cases and prompt awareness of “rare and subtle presentations” of laryngeal lymphoma.
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Gumbarewicz, Ewelina, Agata Jarząb, Andrzej Stepulak, and Wirginia Kukula-Koch. "Zingiber officinale Rosc. in the Treatment of Metabolic Syndrome Disorders—A Review of In Vivo Studies." International Journal of Molecular Sciences 23, no. 24 (December 8, 2022): 15545. http://dx.doi.org/10.3390/ijms232415545.
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Inflammation is a protective reaction of the innate immune system as a response to imbalances caused by a specific stimulus, a disease or a pathogen. A prolonged inflammatory condition may lead to the development of metabolic syndrome, which affects more than one-fourth of the world’s population. This condition leads to the development of multi-organ disorders based on disrupted blood lipid and sugar levels, hypertension and oxidative stress. The review aims to present Zingiber officinale Rosc. as a plant that exhibits a variety of healing properties and restores the organism’s equilibrium. Ginger (GI) rhizomes have been commonly used in traditional medicine to treat arthritis, stomach ache, nonalcoholic fatty liver disease, rheumatism, nervous system syndromes, asthma, diabetes and nausea caused by pregnancy or chemotherapy. This review gathers together data from in vivo experiments related to the application of ginger for the treatment of inflammatory conditions, obesity, diabetes and other related disorders as a consequence of metabolic syndrome, including the confirmed molecular mechanisms of action.
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Younes, Anas, Luis Fayad, Jorge Romaguera, Barbara Pro, Andre Goy, Nam Dang, and Michael Wang. "Long-Term Safety and Efficacy of Single Administration of a Fixed Dose Pegfilgrastim (Neulasta) in Inducing Neutrophil Count Recovery after ABVD Chemotherapy in Patients with Hodgkin Lymphoma." Blood 104, no. 11 (November 16, 2004): 4646. http://dx.doi.org/10.1182/blood.v104.11.4646.4646.
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Abstract Pegfilgrastim (Neulasta) is a pegylated form of G-CSF that has a long half-life allowing for a single administration per chemotherapy cycle. Although the safety and efficacy of pegfilgrastim has been established in association with chemotherapeutic regimens that are repeated every 3 weeks, its safety in patients receiving chemotherapy regimens every 2 weeks is currently under investigation. Of concern is the possibility of stem cell damage because of the long half life that may overlap with subsequent courses of chemotherapy. ABVD chemotherapy is widely used for the treatment of patients with Hodgkin disease. Up to 65% of patients receiving ABVD will require growth factor support to 1) maintain dose intensity 2) to prevent neutropenic fever and 3) to prevent delays in chemotherapy administration. In this study, we used a single dose per cycle of 6 mg pegfilgrastim in first and subsequent cycles of ABVD. Patients were eligible if they were older than 16 years and had previously untreated Hodgkin’s disease patients who are scheduled to receive standard ABVD chemotherapy, adequate bone marrow reserve (ANC > 1,000/uL, Platelet > 100,000/uL, left ventricular ejection fraction > 50%, serum creatinine < 2 mg/dl, serum bilirubin < 2 mg/dl. They were excluded if they had HIV infection, were pregnant women and women or child bearing age who are not practicing adequate contraception, had prior chemotherapy, severe pulmonary disease including COPD and asthma, or history of prior sensitivity to E.coli derived products. All patients received one fixed dose of 6 mg pegfilgrastim 24 hours after ABVD therapy. CBC was performed on a weekly basis, until completion of therapy, and then was monitored every 3–4 months thereafter. Twenty-five patients are enrolled, all of whom are evaluable for efficacy and toxicity. Median age is 26 (range; 19 – 81 years). Men = 14, women = 11. Twenty three pts completed at least 3 full cycles (6 doses of ABVD), and thirteen Pts completed 6 cycles. A total of 225 doses of ABVD are administered. Day 14 ANC count below 1,000/uL occurred in only 5 doses of ABVD (2%). Non-neutropenic infection developed with 7 doses (3%) requiring delay in the subsequent dose of ABVD beyond day 14. Long-term safety is available on 11 pts who had a follow-up ANC counts beyond one year after completion of ABVD treatment. The median ANC after at least one year of follow up was 2,790/uL (range 1,350 to 7,060/uL). Five pts had a follow up beyond 18 months, and their median ANC was 2,300/uL (range: 1,570 to 3,360/uL). Furthermore, PK data from 5 unselected patients were performed on day 14 following the first cycle of ABVD. In all 5 patients, serum pegfilgrastim levels were below clinically significant levels. Our data demonstrate the efficacy of single dose per cycle of pegfilgrastim in maintaining ABVD dose intensity, keeping therapy on schedule, and preventing neutropenic fever. Furthermore, our preliminary long-term follow up data demonstrate the safety of pegfilgrastim administration in conjunction with standard dose chemotherapy given every 2 weeks.
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Younes, Anas, Luis Fayad, Jorge E. Romaguera, Barbara Pro, and Michael Wang. "ABVD with Pegfilgrastim (Neulasta) Support in Newly Diagnosed Hodgkin Lymphoma: Long-Term Safety and Efficacy Results of a Phase-II Study." Blood 106, no. 11 (November 16, 2005): 4790. http://dx.doi.org/10.1182/blood.v106.11.4790.4790.
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Abstract The safety and efficacy of pegfilgrastim (Neulasta) has been established in association with chemotherapeutic regimens that are repeated every 3 weeks. However, the long-term safety of pegfilgrastim in patients receiving chemotherapy regimens every 2 weeks remains under investigation. Of concern is the possibility of stem cell damage because of the long half-life that may overlap with subsequent courses of chemotherapy. ABVD chemotherapy is widely used for the treatment of patients with Hodgkin lymphoma (HL). Up to 65% of patients receiving ABVD will require growth factor support to maintain dose intensity, prevent neutropenic fever, and to prevent delays in chemotherapy administration. In this study, we used primary prophylaxis of 6 mg pegfilgrastim in first and subsequent cycles of ABVD. Patients were eligible if they were older than 16 years and had previously untreated HL patients who are scheduled to receive standard ABVD chemotherapy, adequate bone marrow reserve (ANC > 1,000/uL, Platelet > 100,000/uL, left ventricular ejection fraction > 50%, serum creatinine < 2 mg/dl, serum bilirubin < 2 mg/dl. They were excluded if they had HIV infection, were pregnant women and women or child bearing age who are not practicing adequate contraception, had prior chemotherapy, severe pulmonary disease including COPD and asthma, or history of prior sensitivity to E. coli derived products. All patients received one fixed dose of 6 mg pegfilgrastim approximately 24 hours after ABVD therapy. CBC was performed on a weekly basis, until completion of therapy, and then was monitored every 3–4 months thereafter. Twenty-five patients are enrolled, all of whom are evaluable for efficacy and toxicity. Median age is 26 (range; 19 – 81 years). Men = 14, women = 11. Twenty three pts completed at least 3 full cycles (6 doses of ABVD), and thirteen Pts completed 6 cycles. A total of 225 doses of ABVD are administered. Day 14 ANC count below 1,000/uL occurred in only 5 doses of ABVD (2%). Non-neutropenic infection developed with 7 doses (3%) requiring delay in the subsequent dose of ABVD beyond day 14. Long-term safety is available on 11 pts who had a follow-up ANC counts beyond one year after completion of ABVD treatment. The median ANC after at least one year of follow up was 2,790/uL (range 1,350 to 7,060/uL). Five pts had a follow up beyond 18 months after completion of ABVD therapy, and their median ANC was 2,300/uL (range: 1,570 to 3,360/uL). Furthermore, PK data from 5 unselected patients were performed on day 14 following the first cycle of ABVD. In all 5 patients, serum pegfilgrastim levels were below clinically significant levels. Our data demonstrate the efficacy of single dose per cycle of pegfilgrastim in maintaining ABVD dose intensity, keeping therapy on schedule, and preventing neutropenic fever. Furthermore, our preliminary long-term follow up data demonstrate the safety of pegfilgrastim administration in conjunction with standard dose ABVD chemotherapy given every 2 weeks.
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Marchenko, V. N., E. A. Bruchkus, A. A. Lebedeva, D. A. Davydov, N. L. Shaporova, O. V. Dudina, O. A. Smul’skaya, and M. K. Zinakova. "Eosinophilic granulomatosis with polyangiitis in comorbidpatient: is the immunological diagnostics always unambiguous." Medical Immunology (Russia) 22, no. 2 (April 16, 2020): 383–92. http://dx.doi.org/10.15789/1563-0625-egw-1925.
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Eosinophilic granulomatosis with polyangiitis (EGPA), previously called Churg—Strauss syndrome, represents a rare form of ANCA-associated necrotising vasculitis which affects small vessels. This disease is characterized by typical combination of immunological disturbances, hypereosinophilia, severe bronchial asthma, transient pulmonary infiltrates, and kidney injury which is less frequent than in other forms of necrotising vasculitis.Verification of the diagnosis is often hampered by comorbidities, such as chronic obstructive pulmonary disease (COPD) in the patients with long-term smoking history and occupational hazards.In this article, we report a clinical case of EGPA in elderly patient with preceding COPD which caused diagnostic difficulties for this eosinophilic syndrome. Clinical pattern at the beginning of disease was presented by moderate inspiratory dyspnea and cough with small amounts of mucus sputum, which appeared after longterm exposure to chlorine-containing substances. COPD diagnosis in this patient was based on clinical pattern, long smoking experience, and occupational hazards. However, persistence of the symptoms during the ongoing therapy, as well as multidirectional dynamics of transient pulmonary infiltrates found on repeated CT-scans, prompted us to intensify diagnostic search for a systemic disease. Clinical, laboratory and instrumental signs of bronchial asthma were revealed, as well as hypereosinophilia and sensory polyneuropathy, which, if combined with CT-scan data, allowed us to prove the EGPA diagnosis.This case shows that, despite great value of immune diagnostics, with negative blood tests for ANCA, it is necessary to detect mutually complicating comorbid pathology. EGPA was considered the basic diagnosis, and COPD as accompanying disorder, taking into account such reasons as an unfavorable prognosis for EGPA and the need for long-term chemotherapy with systemic corticosteroids and monoclonal antibodies. ANCA-negative testing in the patient, absence of severe kidney and skin lesions allows to suggest better clinical prognosis in this patient.
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Jimenez‐Rodriguez, Teodorikez‐Wilfox, María Pilar Berges‐Gimeno, Ruth Barranco, Joan Bartra, María del Carmen Diéguez, Inmaculada Doña, Montserrat Fernández‐Rivas, et al. "Management of hypersensitivity reactions to chemotherapy and biologic agents: A survey of ARADyAL (Asthma, Adverse Drug Reactions and Allergy Network) Spanish allergy services." Allergy 76, no. 7 (February 27, 2021): 2249–53. http://dx.doi.org/10.1111/all.14743.
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Gonzalvo, Augusto, Catriona McKenzie, Margot Harris, and Michael Biggs. "Primary Non-Hodgkin's Lymphoma of the Radial Nerve." Neurosurgery 67, no. 3 (September 1, 2010): E872—E873. http://dx.doi.org/10.1227/01.neu.0000374852.65670.7d.
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Abstract OBJECTIVE Primary lymphomas of peripheral nerves are extremely rare, with the bulk of the literature being case reports. The nerve most commonly affected is the sciatic nerve, with 9 cases reported. To date, there are no reports in the English literature of isolated involvement of the radial nerve by a primary lymphoma. CLINICAL PRESENTATION A 69-year-old woman with a history of osteoporosis, irritable bowel disease, asthma, and Graves' disease presented with a 6-month history of paresthesia in her left superficial sensory radial nerve territory, weakness of thumb extension, and localized pain and swelling in the cubital fossa. Examination showed a painful tender mass in the line of the radial nerve in the cubital fossa, grade 4/5 supination, grade 4-/5 extensor carpi radialis longus and extensor carpi ulnaris, and grade 3/5 finger and thumb extension, all consistent with a radial nerve lesion at the level of the cubital fossa. Ultrasonography and computed tomography confirmed an intraneural tumor. Surgery revealed radial intraneural tumor just after the branch to the extensor carpi radialis longus. It was clearly an infiltrating lesion with no plane between tumor and nerve fascicles. Frozen section confirmed malignancy, and an incomplete excision was performed. Histopathology revealed diffuse large B-cell lymphoma. Surgery was followed with negative staging and a chemotherapy program. CONCLUSION Primary B-cell lymphoma of the peripheral nerve is exceedingly rare and to date has not been reported as an isolated occurrence in the radial nerve. We present a patient who is alive and disease free 65 months after incomplete excision and limited chemotherapy.
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Mehrotra, S., G. Agnihotri, S. Singh, and F. Jamal. "Immunomodulatory potential of Curcuma longa: A review." South Asian Journal of Experimental Biology 3, no. 6 (January 4, 2014): 299–307. http://dx.doi.org/10.38150/sajeb.3(6).p299-307.
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Medicinal plants having immunomodulatory properties provide an alterna-tive potential to conventional chemotherapy for a variety of diseases espe-cially in relation to host defense mechanism. Curcumin one of major curcu-minoids of Curcuma longa, reportedly possess several pharmacological prop-erties including anti-inflammatory, anti-cancer, immunomodulatory activi-ties. Curcumin blocks inflammatory enzymes cyclooxygenase (COX), lipooxy-genase (LOX), matrix metalloproteinase (MMP). Curcumin suppresses the proliferation of a wide variety of tumour cells, including breast carcinoma, colon carcinoma, and renal cell carcinoma through cell cycle arrest. It in-duced apoptosis by downregulation of antiapoptotic protein (Bcl-2 and Bcl-xL). Curcumin modulates immune system by suppressing T-cells, proliferating number of B-cells and reducing proliferation of immature B-cell lymphoma cells. Curcumin treatment inhibited the production of cytokines (IL-8, MIP-1α, MCP-1, IL-1β, TNF-α) and dimerisation of TLR’s. Immunoregulatory activi-ty of curcumin is by inhibiting phosphorylation of IKKβ which ultimately leads to suppression of NF-κB (transcriptional activator protein). This activity of curcumin has renewed scientific interest in its potential to prevent and treat the diseases such as arthritis, allergy, asthma & cancer.
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Qin, Kunming, Lijuan Zheng, Hao Cai, Gang Cao, Yajing Lou, Tulin Lu, Yachun Shu, Wei Zhou, and Baochang Cai. "Characterization of Chemical Composition of Pericarpium Citri Reticulatae Volatile Oil by Comprehensive Two-Dimensional Gas Chromatography with High-Resolution Time-of-Flight Mass Spectrometry." Evidence-Based Complementary and Alternative Medicine 2013 (2013): 1–11. http://dx.doi.org/10.1155/2013/237541.
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Pericarpium Citri Reticulatae (Chenpi in Chinese) has been widely used as an herbal medicine in Korea, China, and Japan. Chenpi extracts are used to treat indigestion and inflammatory syndromes of the respiratory tract such as bronchitis and asthma. This thesis will analyze chemical compositions of Chenpi volatile oil, which was performed by comprehensive two-dimensional gas chromatography with high-resolution time-of-flight mass spectrometry (GC × GC-HR-TOFMS). One hundred and sixty-seven components were tentatively identified, and terpene compounds are the main components of Chenpi volatile oil, a significant larger number than in previous studies. The majority of the eluted compounds, which were identified, were well separated as a result of high-resolution capability of the GC × GC method, which significantly reduces, the coelution.β-Elemene is tentatively qualified by means of GC × GC in tandem with high-resolution TOFMS detection, which plays an important role in enhancing the effects of many anticancer drugs and in reducing the side effects of chemotherapy. This study suggests that GC × GC-HR-TOFMS is suitable for routine characterization of chemical composition of volatile oil in herbal medicines.
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Shen, Ti, Zhongzhen Guan, Zhixiang Shen, Yuankai She, and Jun Zhu. "Results of Multicentre Phase IV Study of Rituximab in Combination with CHOP Chemotherapy in Patients with Previously Untreated Non-Hodgkin’s Lymphoma." Blood 104, no. 11 (November 16, 2004): 4624. http://dx.doi.org/10.1182/blood.v104.11.4624.4624.
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Abstract Purpose: Rituximab is a chimeric anti-CD20 monoclonal antibody that was the first antibody approved by the FDA in the United States of America and SDA in China for the treatment of B-cell non-Hodgkin’s Lymphoma (NHL). It has shown significant efficacy and good tolerability in refractory and relapsed NHL. We have conducted a multicenter phase IV trial to evaluate the efficacy and safety of rituximab combined with standard CHOP chemotherapy in patients with newly diagnosed B-NHL. Methods: Patients with newly diagnosed, histologically proven CD20-positive NHL were eligible for the study. All patients received 4–6 infusions of rituximab (375mg/m2 per dose) in combination with CHOP chemotherapy, either concurrently (rituximab administered on the first day of each 21-day CHOP cycle) or sequentially (4–6 once-weekly infusions of rituximab followed by six 21-day cycles of CHOP). Each CHOP cycle consisted of cyclophosphamide 750 mg/m2, doxorubicin 50mg/m2, and vincristine 1.4mg/m2 (maximum 2.0mg/dose) given intravenously on day 1, and prednisone 100mg/day orally on days 1-5. Tumor responses were assessed at the end of treatment. Results: A total of 347 patients were recruited between February 2002 and December 2003. Of these 235 (68%) were male and 94 (27%) aged >60. The main lymphoma subtypes were diffuse large B-cell 196 (56%), follicular 41(12%), small lymphocytic/chronic lymphocytic leukemia 13(4%) and MALT 11(3%). Ann Arbor staging was as follows: stage I, 52 (15%); stage II, 80 (23%); stage III, 90(26%); stage IV, 105(30%); twenty patients (6%) could not be assessed. Of the 347 patients enrolled, 314 were evaluable for response. An objective response was observed in 94% of evaluable patients with a complete response (CR) in 56%, stable disease in 3.8% and progressive disease in 2.5%. The complete response rate was 63% for patients receiving 6 cycles of rituximab and 54% for those receiving four cycles of rituximab. No difference in response rate was observed between the sequential and concurrent groups. The most common adverse events were leucopenia in 122 patients (35%), nausea and vomiting 66 (19%), fever 39 (11%), rash 15 (4%) and asthma 4 (1%). Conclusion: The combination of rituximab and CHOP chemotherapy is an effective and well-tolerated treatment for patients with newly-diagnosed CD20-positive NHL. The safety and efficacy achieved in this study suggests that more than four doses of rituximab may be required for optimal efficacy.
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Morris, Amy L., Mohammed Athar Naeem, Anjali Bal, Tanya Thomas, Alfadel Alshaibani, Bethany Horton, and Michael K. Keng. "Clostridium Difficile Infection in Patients with Acute Myeloid Leukemia." Blood 128, no. 22 (December 2, 2016): 5181. http://dx.doi.org/10.1182/blood.v128.22.5181.5181.
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Abstract BACKGROUND: Clostridium difficile infection (CDI) is the most important cause of nosocomial infectious diarrhea and has been not well studied in patients with neutropenia who have hematologic malignancies in the United States. Previous studies suggest patients undergoing induction chemotherapy for acute myeloid leukemia (AML) are at a high risk of contracting CDI, but these patient's clinical and disease characteristics are not described. This study reports CDI rates and disease characteristics in AML patients at the University of Virginia (UVA). METHODS: A retrospective chart review of 126 consecutive patients undergoing induction or re-induction chemotherapy for AML at UVA from July 2011 to December 2015 was conducted. The primary endpoint was to determine the rate of CDI within ninety days of chemotherapy initiation. CDI was defined by a Clostridium difficile positive PCR in the presence of diarrhea. Secondary endpoints include patient characteristics, comorbidities, risk factors, and disease specific indices associated with CDI. Statistical methods include nonparametric Wilcoxon test, Fisher's exact test, and Holm's sequential Bonferroni procedure as appropriate. Statistical significance was defined as p-value <0.05. RESULTS: Of 126 patients, 31 patients (24.6%) with AML had CDI. 8 patients (25.8%) had one recurrent episode of CDI, 2 patients (6.4%) had two recurrences, and 2 patients (6.4%) had more than two recurrences. 25 patients (80.6%) underwent CT abdominal imaging specifically for the CDI episode, revealing 2 patients (8%) with typhilitis. 2 patients (6.4%) developed toxic megacolon, but no patients underwent colectomy. There was no CDI specific mortality in these 31 patients. During the same 4 year timespan, an additional 27 patients with hematologic malignancies other than AML were identified. These two cohorts (AML and non-AML CDI patients) were not statistically different in terms of patient demographics (age, gender, BMI), medical comorbidities (tobacco use, asthma, COPD, cardiac disorders, CKD, and rheumatologic conditions), and CDI characteristics (recurrences, prior antibiotics prophylactic and treatment regimens, PPI medication usage, CDI treatment regimen and treatment duration, development of typhilitis and toxic megacolon, and mortality). The only statistically significant difference is the presence and increased duration of neutropenia in the AML CDI patient cohort (p-value < 0.001). DISCUSSION: The study concludes that the incidence of CDI in patients with AML undergoing induction chemotherapy is greater than hospitalized patients without AML as reported in the literature. However, when compared to a matched cohort of hospitalized patients with non-AML hematologic malignancies, the incidence of CDI is similar between these two groups. This result is striking as AML induction chemotherapy regimens are typically more intense, resulting in more profound and longer neutropenia. Even with increased cytopenias, the CDI rate and disease characteristics are not affected when AML CDI patients are compared to non-AML CDI patients. This suggests that cytopenias should not be the focus for CDI patients, rather hematologic malignancies as whole lead to increased CDIs and heightened awareness is warranted when caring for patients with hematologic malignancies and complaints of diarrhea. Patients in both AML and non-AML CDI cohorts have relatively favorable outcome, with no patient mortality attributable to CDI. Further studies are needed to evaluate what, if any, predictive risk factors can increase CDI in the setting of AML. Disclosures No relevant conflicts of interest to declare.
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Qureshi, Irfan, and Ziat T. Awad. "Predictors of Failure of the Laparoscopic Approach for the Management of Small Bowel Obstruction." American Surgeon 76, no. 9 (September 2010): 947–50. http://dx.doi.org/10.1177/000313481007600926.
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Small bowel obstruction (SBO) is a common cause of hospital admission. Our objective is to determine variables that correlate with failure of the laparoscopic approach for SBO. Twenty-three consecutive patients underwent diagnostic laparoscopy with curative intent for treatment of SBO by a single surgeon over a 3-year period. The laparoscopic approach was successful in 18 patients (78%); there were five (22%) conversions to laparotomy. The causes of obstruction included adhesive band in 16 patients; and small bowel lymphoma, metastatic esophageal cancer, small bowel gangrene, Meckel diverticulum, gallstones ileus, and incarcerated incisional hernia in two. Using the Fisher two-sided test, no significant predictor for conversion was identified using gender, American Society of Anesthesiologists class, previous bowel obstruction, history of adhesiolysis, abdominal distention, pelvic surgeries, chemotherapy, radiation, malignancy, chronic obstructive pulmonary disease, asthma, coronary artery disease, hypertension, or hypercholesterolenemia. The Wilcoxon two-sided test did not show significance for age, weight, number of previous abdominal surgeries, or small bowel diameter. The postoperative hospital stay was significantly shorter in the laparoscopic group compared with those who needed conversion (3 vs 9 days) with P = 0.0019. No mortality was noted in any patients. The laparoscopic is safe and feasible for the management of SBO. We believe that the laparoscopic approach should be offered to all patients with SBO unless there is an absolute contraindication to laparoscopic surgery.
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Schlick, Konstantin, Martin Pichler, Sonja Reitter, Peter Neumeister, Gerald Hoefler, Christine Beham-Schmid, Werner Linkesch, Dirk Strunk, and Ariane Aigelsreiter. "Histiocytis Sarcoma-Targeted Therapy: Novel Therapeutic Options? A Series of 4 Cases." Blood 118, no. 21 (November 18, 2011): 5005. http://dx.doi.org/10.1182/blood.v118.21.5005.5005.
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Abstract Abstract 5005 Case 1: A 23-year old man presented with a newly diagnosed Histiocytic Sarcoma (HS) of the neck. Tracheotomy had to be performed due to a massive swelling of the neck and pharynx. Chemotherapy was initiated in combination with local irradiation therapy with the aim of stabilization of the fulminate disease course.To gain further insight in the tumour's biology an extensive immunohistochemistry exploration was done. A positive reaction with antibodies (AB) against PDGFRalpha and VEGFR2 and VEGFR3 was detected with variable staining intensities and number of tumor cells. According to this marker profile the tyrosinkinase inhibitor Imatinib and the immunomodulating agent thalidomide were added to the chemotherapy regimen. The therapy regime of both agents, which can only be applied orally, could only partially be followed due to the massive pharyngeal mass and repeated emesis. After two cycles of chemotherapy the patient showed progressive disease and succumbed to fulminant pericardial effusions and progressive disease. Case 2: A 53-years old female with a history of exogenous allergic asthma bronchiale was admitted to a hospital. CT scan was performed and the presumption diagnosis of pneumonia was made. Due to thickened pleura with suspect pericardial infiltrations the differential diagnosis of mesothelioma was reported and a video assisted thoracoscopy with biopsies were obtained. Immunohistochemistry was positive for EGFR, PDGFRalpha, PDGFRbeta, and VEGFA20. Two cycles of an experimental therapy regime containing Imatinib and Bevacizumab, combined with chemotherapy were applied. Restaging imaging studies showed a stable tumour load in the CT and PET scans. The patient could be discharged under continuation of daily imatinib therapy and bevacizumab every 14 days. Five months later the patient showed progressive disease and succumbed. Case 3: A 48-year old male patient presented with a newly diagnosed HS of the right upper leg. Tumour tissue could not be removed in sano due to infiltration of the surrounding fat tissue. Seven months later the patient was hospitalised again with a local recurrent tumor. According to the literature two cycles of chemotherapy for extramedullary myeloid leukaemia was applied and the patient was discharged in a complete remission. Seven months later the patient developed severe back pain and a biopsy of the spine was taken. Histology reported metastasis of HS. A polychemotherapy was applied coming up with a no change course of the disease. An immunohistochemical workup showed a positive reaction with antibodies against EGFR, PDGFRalpha PDGFRbeta and VEGFC1. A Bevacizumab monotherapy was applied for three times, however showing no response. Finally, the patient died due to progressive disease. Case 4: A 68-year old female was admitted to hospital after diagnosis of a HS of the intestinal tract. A tumor of the terminal ileum of six cm in greatest diameter had been surgically removed in sano. Five weeks later the patient presented with pathologically enlarged mediastinal and abdominal lymph nodes in CT scan. Progressive disease was confirmed by a PET scan. An immunohistochemical workup showed a positive reaction with AB against PDGFRalpha, PDGFRbeta, VEGFR2 and VEGFR3 An experimental treatment approach of two cycles with a combination of Bevacizumab and chemotherapy was applied. In addition a low dose maintenance therapy with Sorafenib 2×400mg daily was administered due to pancytopenia. Therapy had to be discontinued after one month due to elevation of pancreatic enzymes. A restaging CT scan showed no pathological enlarged lymph nodes and a PET scan, two months after initiation of therapy, revealed a complete metabolic remission. Five months later on control revaluation remission was stable by CT and PET scan. Nowadays, almost two years later, the patient is still in an ongoing complete remission without any further therapy. Disclosures: No relevant conflicts of interest to declare.
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Hasle, Henrik, Heidi Glosli, Kirsi Jahnukainen, Marianne Jarfelt, Guđmundur Jónmundsson, Johan Malmros-Svennilson, Karsten Nysom, and Lene Molgaard-Hansen. "Good General Health In Survivors of Childhood AML Treated with Chemotherapy Only: A NOPHO-AML Study." Blood 116, no. 21 (November 19, 2010): 1076. http://dx.doi.org/10.1182/blood.v116.21.1076.1076.
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Abstract Abstract 1076 Background. More than 60% of children with acute myeloid leukemia (AML) become long-term survivors and most are cured with chemotherapy only. With this improvement, the late mortality and morbidity after the very intensive treatment deserve attention. Previous studies have reported late effects after childhood AML, but most side effects were probably caused by cranial irradiation or hematopoietic stem cell transplantation (HSCT). Limited data exist about the long-term mortality, morbidity, and social outcomes in AML survivors treated with chemotherapy only. The objectives of this study were to report the occurrence of late mortality and compare the self-reported health care use and health experience, lifestyle behavior, and social outcomes of AML survivors with those of their sibling controls. Methods. Children treated for AML according to the Nordic protocols NOPHO-AML-84, -88, and -93, and alive by 30 June 2007 were identified in the NOPHO-AML database. We excluded patients with myeloid leukemia of Down syndrome, Fanconi anemia, preceding myelodysplastic syndrome, therapy-related AML, patients receiving allogeneic or autologous HSCT, and patients who had experienced a relapse or had a secondary malignancy. A total of 102 (74%) of the 138 eligible AML survivors accepted the invitation for a physical and paraclinical examination and completed a questionnaire concerning health and social status. One sibling per patient was invited to complete a similar questionnaire which was accepted by 85 (91%) of 93 eligible siblings. Results. The median follow-up was 11 (range 4–25) years after diagnosis. Five-year AML survivors' overall survival rate was 94% at 20 years after diagnosis (95% confidence interval; 84–98%). Four children died more than five years after end of treatment; one from sequelae of initial cerebral bleeding, two from side effects of treatment including one with hearth failure, and one from secondary malignancy. AML survivors had no increased rate of hospitalization compared with sibling controls but more received prescription drugs, especially for asthma (23% vs. 9%, p=0.03). Self-reported health experience was excellent or very good in 77% and comparable with that of siblings (Table). The rate of current smokers was similar in the two groups (23% vs. 24%). Sixty-seven percent of the AML survivors >20 years of age and 73% of their siblings reported to be undertaking or having completed an education, defined as vocational training or academic education lasting at least three years (p=0.8). Among those >20 years of age, the frequency of marriage or cohabitation did not differ between AML survivors and siblings (39% vs. 37%). Conclusions. Children treated on NOPHO-AML protocols without HSCT and surviving at least five years after diagnosis had a very low mortality rate. Their self-reported health was good, and health care use was limited and comparable to that of sibling controls, but they were more often receiving prescription drugs for minor illnesses. Most AML survivors seemed to have coped well with their transition into adulthood, and they reported educational achievement, employment and marital status comparable to those of their sibling controls. Disclosures: No relevant conflicts of interest to declare.
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Jeong, Sunyoung, Seug Yun Yoon, Min Young Lee, Kyoung Ha Kim, Nam Su Lee, and Jong Ho Won. "Review of End-of-Life Care and Supportive Care during Disease Course in Elderly Patients with Multiple Myeloma." Blood 138, Supplement 1 (November 5, 2021): 4731. http://dx.doi.org/10.1182/blood-2021-150237.
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Abstract Background Multiple myeloma (MM) is a plasma cell malignancy of which the median age at diagnosis is 70 years old. The novel agents had contributed significant improvement in the overall survival of MM. However, there is a disparity in survival between young and old patients, and early mortality is high in patients older than 70. Therefore, before making a treatment plan for elderly MM patients, it is crucial to consider both quality of life and even end-of-life (EOL) care. This study evaluated EOL characteristics and real-world supportive care in elderly MM patients. Methods We retrospectively reviewed medical records of patients diagnosed with MM at an age older than 70 between January 2011 and April 2021. We identified baseline characteristics, symptom burdens, factors associated with hospitalizations during the disease course, and several indicators of EOL; place of death, length of hospitalization, cause of death, chief complaints, agreement of "do-not-resuscitate (DNR)", other aggressive and less aggressive interventions in their last hospitalization. Result A total of 52 patients were included. The median age at diagnosis is 76 years old. 12 (23.08%) patients showed initial Eastern cooperative oncology group (ECOG) performance status 3 or 4. 30 (57.69%) patients had hypertension, 18 (34.62%) had diabetes, and 8 (15.38%) had chronic lung disease; asthma, COPD, and bronchiectasis. 3 (5.77%) patients had initial International staging system (ISS) stage 1 disease, 16 (30.77%) had 2, and 29 (55.77%) had 3. Only 2 (3.85) patients never received chemotherapy; one of them showed initial ECOG 3, and the other was unknown. The median overall survival was 16.69 months. 27 (51.92%) patients visited the emergency department during their disease course at least once, and 19 (36.54%) were admitted intensive care unit more than once. Only 4 (7.59%) patients were never admitted hospital during their disease course except for chemotherapy. The mean number of hospitalization was 3.23, and the reason for 41.67% of hospitalization was to control myeloma-related symptoms; general weakness, acute kidney injury, pain, fracture, cord compression, and anemia. The rate of hospitalization day after diagnosis was 9.85%. The EOL characteristics of 24 (46.15%) deceased at the hospital were analyzed. An average hospitalization length was 41.96 days. Other EOL characteristics are detailed in table 1. Conclusion Elderly MM patients spent almost 10% of their disease duration at the hospital to control disease-related symptoms. It might explain why elderly MM patients received aggressive therapy despite their age and poor performance status. To enhance their quality of life, we need to focus more on supportive care and make a decision for chemotherapy carefully. Furthermore, for EOL care, discussion for performing an aggressive intervention with patients should be encouraged. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.
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Becker, Pamela s., Frederick R. Appelbaum, Sylvia Chien, Xin Zhao, Halvard Bonig, Ryuta Mukasa, and Thalia Papayannopoulou. "Oral Small Molecule Inhibitor of VLA-4 Overcomes Adhesion Mediated Chemotherapy Resistance of Acute Myeloid Leukemia (AML) Blasts in Vitro, without Impairment of Normal Blood Cell Recovery When Combined with Chemotherapy in Vivo." Blood 112, no. 11 (November 16, 2008): 858. http://dx.doi.org/10.1182/blood.v112.11.858.858.
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Abstract Adhesion within the bone marrow (BM) microenvironment confers protection from chemotherapy induced apoptosis for a number of hematological malignancies, including AML. The majority of human AML blasts express VLA-4, the α4β1 integrin through which hematopoietic cells bind to VCAM-1 and/or fibronectin within the BM. Our laboratory and others have previously conducted in vitro studies demonstrating that antibody to VLA-4 enhanced chemotherapy induced cytotoxicity and apoptosis for AML cell lines and primary human AML blasts. One humanized anti-VLA-4 antibody (ab), natalizumab, is currently approved, with clinical applications in relapsing multiple sclerosis and Crohn’s disease, while a number of small molecule inhibitors of VLA-4 are under development with oral bioavailability for conditions such as asthma and inflammatory disorders. These oral agents would have the advantage of a shorter half-life than the humanized antibody, be available for just the period of chemotherapy treatment, and perhaps reduce the incidence of long-term toxicity. We herein present data that demonstrate the ability of an oral small molecule inhibitor of VLA-4, D11-5908 (Daiichi Sankyo Co., Ltd.) to potentiate chemotherapy toxicity in AML blasts in vitro, comparable to anti-VLA-4 ab in this first direct comparison study, its ability to mobilize normal murine stem cells or engrafted AML cells in xenograft mice, and no impairment of blood cell recovery in vivo in normal mice receiving a combination of D11-5908 and ara-C compared to ara-C alone. In independent experiments, the viability of AML blasts isolated from 8 patients pre-incubated with D11-5908, then treated with AraC (4 μM) or a combination of AraC (4 μM) and daunorubicin (5 μM), decreased by 27.8% ± 7.5% for cells on recombinant human fibronectin peptide CH-206, Retronectin™ (Rn), compared to a decrease of 10.4% ± 6.5% after pre-incubation with isotype control ab (p=0.0046 by two tailed paired t-test). This effect with D11-5908 was similar to the reduction in cell survival with the anti-VLA-4 ab, which decreased viability after chemotherapy by 20.2% ± 7.8% (p=0.014 compared to isotype control, and p=0.27 compared to D11-5908). Antibody to VLA-4 has been demonstrated to mobilize normal hematopoietic stem cells in vivo, in mice, non-human primates, and humans, a function that would be considered fundamental to an active VLA- 4 inhibitor. To test the ability of D11-5908 to mobilize both normal and AML cells in vivo from the marrow into the blood, we assayed for mobilization in both normal mice and in a xenograft model of human AML engrafted in NOD-scid β2microglobulin−/− mice. D11- 5908 mobilized both human AML cells, as well as normal murine progenitor cells in the NOD-scid mouse model. Mobilizing the human AML cells may render them susceptible to chemotherapy outside the protected BM microenvironment. Two of 4 NODscid mice previously engrafted with human AML cells mobilized human CD117 positive AML cells up to 50–60% of the peripheral blood mononuclear cells after treatment with D11- 5908, compared to negligible circulating AML prior to D11-5908 treatment. In addition, 2 untreated NODscid β2microglobulin−/− mice increased circulating murine colony forming cells (CFCs) from 253 ± 31/ml to 542 ± 106/ml of peripheral blood after three doses of oral gavage with D11-5908 (p=0.059). Four normal BALB/c mice, increased CFCs from 233/ml ± 14 to 471/ml ± 273 at 1 hour post 3rd dose of twice daily oral gavage with D11-5908. Lastly, D11-5908 did not impair normal blood cell recovery after AraC for BALB/c mice treated simultaneously with D11-5908 (100 mg/kg twice daily X 3 days) and AraC (20 mg/mouse IP), as compared to AraC alone in 5 independent experiments. The values for neutrophil count (ANC), nadir d.5-0.63 vs. 0.88 (p=0.30), recovery d.7-1.9 vs. 2.4 (p=0.13), and for a second experiment, nadir d. 3 -0.89 vs. 1.37 (p=0.095), recovery d. 5-1.23 vs.1.00 (p=0.38) did not differ significantly. The p values greater than 0.05 indicate that the blood cell recovery from nadir was equivalent for ara-C with or without D11-5908, as it was for white blood cells and hemoglobin; platelet counts were unaffected by these doses. These preclinical in vitro and in vivo data support the development of a promising therapeutic approach consisting of the combination of a novel oral adhesion inhibitor with chemotherapy for the treatment of AML.
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Samhouri, Bilal F., Natalya Azadeh, Thorvardur R. Halfdanarson, Eunhee S. Yi, and Jay H. Ryu. "Constrictive bronchiolitis in diffuse idiopathic pulmonary neuroendocrine cell hyperplasia." ERJ Open Research 6, no. 4 (September 24, 2020): 00527–2020. http://dx.doi.org/10.1183/23120541.00527-2020.
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BackgroundDiffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is characterised by multifocal proliferation of neuroendocrine cells and belongs in the spectrum of pulmonary neuroendocrine tumours. Some patients with DIPNECH develop airflow obstruction but the relationship between the two entities remains unclear.MethodsWe performed a computer-assisted search of the Mayo Clinic's electronic medical records for biopsy-proven cases of DIPNECH. We extracted clinical, pulmonary function, imaging and histopathological data along with treatments and outcomes.ResultsAmong 44 patients with DIPNECH 91% were female and the median age was 65 years (interquartile range 56–69 years); 73% were never-smokers. Overall, 38 patients (86%) had respiratory symptoms including cough (68%) and dyspnoea (30%); 45% were previously diagnosed to have asthma or COPD. Pulmonary function testing showed an obstructive pattern in 52%, restrictive pattern in 11%, mixed pattern in 9%, nonspecific pattern in 23%, and was normal in 5%. On chest computed tomography scan, 95% manifested diffuse nodules and 77% manifested mosaic attenuation. For management, 25% of patients were observed without pharmacological therapy, 55% received an inhaled bronchodilator, 41% received an inhaled corticosteroid, 32% received octreotide; systemic steroids, azithromycin, or combination chemotherapy was employed in four patients (9%). Of 24 patients with available follow-up pulmonary function tests, 50% remained stable, 33% worsened and 17% improved over a median interval of 21.3 months (interquartile range 9.7–46.9 months).ConclusionDIPNECH occurs mostly in women and manifests diffuse pulmonary nodules and mosaic attenuation on imaging. It is commonly associated with airflow obstruction due to constrictive bronchiolitis, which manifests limited response to current pharmacological therapy.
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Keegan, Theresa H. M., Lori S. Muffly, Qian Li, Elysia Alvarez, Ann M. Brunson, Marcio Malogolowkin, and Ted Wun. "Medical Conditions Among Survivors of Adolescent and Young Adult Non-Hodgkin Lymphoma (NHL), Acute Lymphoblastic Leukemia (ALL) and Acute Myeloid Leukemia (AML)." Blood 132, Supplement 1 (November 29, 2018): 839. http://dx.doi.org/10.1182/blood-2018-99-111553.
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Abstract Introduction: Adolescent and young adult (AYA) cancer survivors are at an increased risk of developing subsequent medical problems, including asthma/chronic obstructive pulmonary disorder, cardiovascular disease, diabetes and second cancers. However, few population-based studies have focused on these risks in AYAs with NHL, ALL or AML or considered whether the occurrence of these and other medical conditions differ by sociodemographic factors. Methods: Data for patients aged 15-39 when diagnosed with NHL (n=4,459), ALL (n=1,100) and AML (n=1,107) during 1996-2012 and surviving a minimum of 2 years were obtained from the California Cancer Registry and followed in California hospital discharge databases. Discharge diagnoses were used to classify medical conditions as cardiac (hypertensive disease, ischemic heart disease, other heart disease), neurologic (stroke, seizure), endocrine (hypothyroidism, diabetes, ovarian/testicular dysfunction, other metabolic diseases), respiratory (asthma, chronic obstructive pulmonary disease), renal (chronic kidney disease, hemodialysis, kidney transplant), liver (chronic liver disease, pancreatitis, cirrhosis, liver transplant), and avascular necrosis. Second cancers were obtained from the cancer registry. We estimated the cumulative incidence (CMI) of developing each condition 10-years after diagnosis, accounting for death as a competing risk. We determined the impact of race/ethnicity, neighborhood socioeconomic status (SES), health insurance status and stem cell transplant (SCT) on the occurrence of each medical condition after adjusting for other demographic and clinical factors using multivariable Cox proportional hazards regression. Results: The most common medical conditions among AYA survivors at 10-years were cardiac (CMI NHL: 11.6%; ALL= 20.5%; AML= 18.2%), endocrine (CMI NHL: 18.6%; ALL= 33.0%; AML= 25.9%) and respiratory (CMI NHL: 5.1%; ALL= 7.7%; AML= 6.8%) diseases. Avascular necrosis had the highest CMI in ALL patients (CMI NHL: 1.2%; ALL= 8.7%; AML= 2.5%). Neurologic (CMI NHL: 2.1%; ALL= 4.5%; AML= 4.9%) and liver (CMI NHL: 2.0%; ALL= 5.6%; AML= 4.4%) were more common in survivors of ALL and AML than NHL. Second cancers (2.3-2.5%) and renal diseases (2.2-3.5%) were less common at 10-years. NHL survivors with advanced stage disease had a higher incidence of all medical conditions, except second cancers. Chemotherapy was associated with a higher CMI of cardiac and endocrine conditions among NHL survivors; these associations could not be assessed in ALL and AML patients as nearly all patients received chemotherapy. Initial radiation therapy was not associated with a higher CMI of medical conditions in NHL or ALL survivors, but was associated with a higher CMI of respiratory, renal and endocrine diseases in AML survivors. In multivariable models, public or no insurance (vs private) was associated with a higher risk of most medical conditions in NHL and ALL survivors, but not AML survivors (Table). The risk of developing medical conditions varied by race/ethnicity, with Hispanics ALL survivors (vs non-Hispanic whites) at a higher risk of cardiac, renal, liver, endocrine, second cancers and neurologic diseases and black AML survivors at a higher risk of all medical conditions, except endocrine diseases. AYAs with NHL who resided in lower SES neighborhoods were at a higher risk for developing cardiac, respiratory and endocrine diseases; AML survivors in lower SES neighborhoods had a higher risk of respiratory diseases. Across all cancers, AYAs undergoing a SCT were at a higher risk of most medical conditions. Conclusion: This study found that sociodemographic factors were associated with the risk of developing medical conditions in AYA NHL, ALL and AML survivors. As expected, the risk of medical conditions varied by cancer type and treatment, with those undergoing SCT having a higher risk of medical conditions regardless of cancer type. NHL and ALL survivors who were uninsured or publicly insured were at a consistently higher risk of developing medical conditions, as were Hispanic ALL survivors and Black AML survivors. Our findings highlight the higher burden of medical conditions in subgroups of cancer survivors that may relate to reduced access to preventive care, early detection/intervention and long-term surveillance. Disclosures Muffly: Shire Pharmaceuticals: Research Funding; Adaptive Biotechnologies: Research Funding.
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Aneja, A., A. Arriola, and A. Jhala. "Pulmonary Granuloma Associated with Pneumocystis Jirovecii in a Patient with Peripheral T-Cell Lymphoma: Presentation of a Rare Case with Review of the Literature." American Journal of Clinical Pathology 154, Supplement_1 (October 2020): S39. http://dx.doi.org/10.1093/ajcp/aqaa161.082.
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Abstract Casestudy: Although Pneumocystis jirovecii (PJ) is a known opportunistic pulmonary infection among immunocompromised patients, it is a rare (<5%) cause of pneumonia in this cohort. Majority of cases are observed in patients with HIV or solid organ transplant recipients. Granuloma formation in patients infected with PJ is even rarer. We present a case of multiple pulmonary granulomas associated with PJ in a non-HIV patient. A 49-year-old female with a history of asthma presented with worsening dyspnea. Initial imaging revealed multifocal bilateral areas of consolidation and a diagnostic bronchoalveolar lavage (BAL) demonstrated PJ organisms. Additional investigation was pursued to determine the etiology of this infection in a seemingly immunocompetent patient. New findings noted during hospitalization included a new maculopapular skin rash, significant weight loss, and lymphopenia. A bone marrow biopsy revealed a clonal proliferation of plasma cells. Subsequent imaging revealed mediastinal adenopathy. There was no improvement in symptoms despite treatment for pneumonia and a month later, a lung wedge biopsy revealed organizing acute lung injury and multiple non-caseating granulomas without lymphoid rimming, asteroid, or Schaumann bodies. Silver stain highlighted numerous PJ organisms within and outside of the granulomas. An inguinal lymph node and skin biopsies eventually revealed involvement by peripheral T-cell lymphoma (PTCL). Repeat BAL revealed clearance of organisms after additional therapy; however, the PTCL was refractory to chemotherapy and palliative care was pursued. To date, we could only find <30 cases of pulmonary PJ granulomas in patients with hematologic malignancies. Most are in patients with B cell lymphomas and just 1 report in a patient with adult T-cell leukemia/lymphoma. In summary, this case highlights that PJ associated pulmonary granulomas are uncommon, can be a harbinger of an underlying immunocompromised state, such as a lymphoma, and are even rarer to be associated with PTCL.
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Yalcin, D., A. Kargi, B. Savas, A. Bisgin, M. Ozdogan, S. Coskun, and E. Terzioglu. "The prevalance of chronic autoimmune urtiker and angioedema among lung and breast carcinoma cases." Journal of Clinical Oncology 27, no. 15_suppl (May 20, 2009): e20707-e20707. http://dx.doi.org/10.1200/jco.2009.27.15_suppl.e20707.
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e20707 Background: Although the risk of allergy and atopy in cancer patients has been studied in various prospective studies previously, no significant association was found between leukemia, breast, colorectal, lung cancers and allergic disorders or atopy. Our purpose in this study was to investigate the prevalance of chronic urticeria and angioedema in breast and lung carcinoma of adults in Mediterrianean Coast of Turkey, Antalya. Methods: 86 breast and 62 lung carcinoma patients that had diagnosed and underwent chemotherapy in Akdeniz University Oncology Clinic were studied. Blood eosinophil, total IgE, ANA, C3, C4, hepatitis markers and autologous skin test were examined in the cases with probable chronic autoimmune urticeria, angioedema. The data were statistically assessed with SPSS version 13.00. Results: Overall 148 patients were included. Median age was 62.4±14.6 years, 60.1% of the patients were women (47.2% of which is not working). 55.6% of the patients are living in apartments. In general, 5.4% (8 case) of the investigated population were diagnosed as autoimmun urticeria; Seven of the 8 of these were breast carcinoma cases (7 out of 86 breast Ca). In contrast, only one of them was lung carcinoma (1 out of 62 lung Ca). Total IgE level was 122 ± 21.4. None of the cases with positive autologous skin test has ANA positivity. Similarly, these cases were also HBV and HCV seronegative. Accompanying angioedema was present 3 cases (with no drug or food history). One case has a hashimato tiroiditis who underwent LT4 replacement. Another patient with autoimmun urticeria has allergical asthma together with 5 cases of allergical rhinitis and conjunctivitis. Conclusions: In this study the frequency of autoimmune urticeria is much higher in breast carcinoma cases compared to patients with lung carcinoma. Further researchs are needed to verify these results and to determine why such association exist. No significant financial relationships to disclose.
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Alabbas, Fahad, Omar Alsharief, Isabelle Meyts, Fatma Albatniji, Michael Hershfield, Adnan Mansoor, and Ghaleb Elyamany. "Deficiency of Adenosine Deaminase 2 (DADA2) Presenting As Familial Hodgkin Lymphoma." Blood 132, Supplement 1 (November 29, 2018): 5373. http://dx.doi.org/10.1182/blood-2018-99-116431.
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Abstract Familial Hodgkin Lymphoma (HL) accounts for 4.5% of HL. Both genetic susceptibility and shared environmental factors can play a role. The usual presentation of HL is cervical lymphadenopathy/ mediastinal mass. Subdiaphragmatic presentation is rare and hepatosplenomegaly is associated with advanced HL. Adenosine deaminase 2 (ADA2) act as an outside extracellular growth factor for integrity of endothelial cells and in the development of certain immune cells. Deficiency of ADA2 (DADA2) is a recently described inborn error of immunity caused by biallelic mutations in adenosine deaminase 2 (ADA2) gene (formerly known as CECR1). It is an auto-inflammatory disorder with a spectrum of vascular, inflammatory, hematological and immunodeficiency phenotypes. The condition is inherited in an autosomal recessive pattern.The association of DADA2 with lymphoproliferation such asT-LGL like condition and ALPS like disease have been reported, however, HL has not previously been reported in DADA2. Herein we describe two siblings with DADA2 who presented with Hodgkin Lymphoma. The first patient is the third child of Saudi first degree related parents. He is known to have bronchial asthma on bronchodilators. At the age of 5 years, he was referred from primary care clinic for investigation of hepatosplenomegaly. He was otherwise well with growth along the fifth centile. His complete blood count (CBC) showed mild lymphopenia, other lab results including liver function tests were within normal. Few months later, he developed non-tender mobile cervical lymph nodes enlargement. Viral serology including EBV was negative based on PCR testing. Lymph node biopsy revealed the diagnosis of HL, mixed cellularity type, EBV negative (Figure 1). Whole exome analysis sequencing identified a homozygous variant in ADA2 gene c.1447_1451del. This variant has been confirmed by Sanger sequencing. Plasma assay of ADA2 enzyme activity revealed undetectable levels compatible with ADA2 deficiency. The patient started on prednisone 2 mg/kg/day, which showed good response in the form of being off blood support and regression of splenomegaly. Few months later, the course was complicated by recurrent infections. The patient remained stable for three years on small dose of prednisone, monthly IVIG due to hypogammaglobulinemia. Recently, etanercept was started to control disease progression. Nine months after the diagnosis of first patient, his younger brother who is known to have mild bronchial asthma on bronchodilators presented at the age of five years with hepatosplenomegaly and generalized lymphadenopathy. Lymph node biopsy revealed the diagnosis of classical HL, lymphocyte-rich subtype. Similar to his sibling, whole exome analysis identified the same mutation (a homozygous variant in ADA2 gene c.1447_1451del). This variant has been confirmed by Sanger sequencing and plasma level of ADA2 enzyme activity was undetectable. After the diagnosis of DADA2, screening for serum immunoglobulin levels showed hypogammaglobulinemia. The patient continues to be off treatment. Both patients were treated with chemotherapy with or without radiotherapy showing good response and they remained in remission at respectively and months after cessation of chemotherapy. This study is important for several reasons. First, this is the first report of HL in the context of DADA2. This again widens the clinical spectrum of DADA2. Interestingly, the boys presented two different forms of HL at the cellular level with no evidence of viral infection. The reported siblings presented with subdiaphragmatic diseases, which is uncommon in HL but in line with the sites of lymphoproliferation in DADA2. In addition, the age of presentation in the two siblings is uncommon in HL (less than 10 years). Second, we report an novel mutation in ADA2 gene. It creates a shift in the reading frame starting at codon Ser483. The new reading frame ends in a stop codon 4 positions downstream. This description and the description of the HL occurrence further expands the spectrum of DADA2. Our data, call for judicious exclusion of ADA2 deficiency in the HL patient with an aberrant course and additional symptoms / signs. In summary, we report familial HL in two patients with a novel deleterious mutation in ADA2 gene. This expands the spectrum of this disease to include cancer and should alert the hemato-oncologist to the possibility of DADA2 as an underlying diagnosis in HL. Figure 1. Figure 1. Disclosures No relevant conflicts of interest to declare.
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Cioclu, Maria Cristina, Francesco Cavallieri, Manuela Napoli, Claudio Moratti, Rosario Pascarella, Franco Valzania, and Marialuisa Zedde. "Mechanisms and Neuroimaging Patterns of Hypereosinophilia-Related Ischemic Stroke: A Narrative Review through Three Cases." Journal of Clinical Medicine 11, no. 19 (September 23, 2022): 5595. http://dx.doi.org/10.3390/jcm11195595.
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Background: Hypereosinophilic syndromes (HES) are a group of relatively rare disorders in which neurological manifestations, including ischemic stroke, are common. The hypothesized pathophysiological mechanisms are hypercoagulability, cardioembolism (mainly mediated by myocardial involvement) and damage to the endothelium. A variable ischemic pattern has been described, including an association of territorial and border zone ischemic stroke. Methods: Three patients who presented to our department with acute stroke were selected aiming to show these three different mechanisms inferred from the stroke pattern on brain Magnetic Resonance Imaging (MRI) and to simultaneously illustrate the three main causes of HES. Results and Discussion: The first patient is a 55-year-old man with an abrupt onset of aphasia due to an acute ischemic stroke involving the left parietal lobule and the angular gyrus; recent lab test had shown hypereosinophilia. An extensive workup excluded primary and secondary causes of hypereosinophilia so a diagnosis of idiopathic hypereosinophilia was done and he was treated with high doses of steroids. The second patient had severe hypereosinophilia and developed multiple small, scattered ischemic lesions, mainly in border zone zones. The history of severe asthma and recurrent sinusitis supported the diagnosis of EGPA (Eosinophilic Granulomatosis with Polyangiitis); considering the severe clinical conditions and the presumptive role of hypereosinophilia in determining her symptoms, steroid treatment was promptly started, with good clinical response. The third patient also presented with multiple metachronous ischemic lesions, both in cortical and border zone distribution and marked eosinophilia; the diagnostic work-up found an ovarian cancer. She was treated with steroids and then underwent surgery and adjuvant chemotherapy. Conclusions: HES should be considered in stroke etiological evaluation, although it is a rare disorder, and border zones pattern without large artery steno-occlusion on neuroimaging may help to raise the suspicion in the neurovascular diagnostic pathway. A thorough research of the sources of hypereosinophilia should be performed to select the appropriate therapy.
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Priyadarshini Kar, Padmaja, Bandana Rath, Y. Roja Ramani, and C. S. Maharana. "Amelioration of Cyclophosphamide Induced Immunosupression by the Hydro-Alcoholic Extract of Gymnema Sylvestre Leaves in Albino Rats." Biomedical and Pharmacology Journal 12, no. 1 (March 5, 2019): 251–58. http://dx.doi.org/10.13005/bpj/1635.
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Cyclophosphamide (CP), the most commonly used anti-neoplastic agent causes immunosuppression and toxic effects on various organs that are the limiting factors of cancer treatment. It can be hypothesized that addition of new immunopotentiating agents with detoxification properties would have beneficial role in cancer therapy. Many researchers have proved that, if certain plant products are combined with cancer chemotherapeutic agents, reduce toxicities and improve tumour response. In Ayurveda, Gymnema sylvestre is commonly used for diabetes, obesity and asthma. Also it possesses anti-inflammatory, astringent and digestive properties. Reports on the immunostimulatory activity of Gymnema sylvestre leaves are available from some in vitro and in vivo experiments. With this background the present study was undertaken to evaluate the potential beneficial role of hydro-alcoholic extract of Gymnema sylvestre leaves (GSE) on cyclophosphamide induced immunnosupression in rats. In this experiment, five groups (n=6 in each) of wistar albino rats were randomly divided to receive drugs and vehicle orally for 21 days. Gr I and II received vehicle. Gr III, IV and V were administered with Levamisole 50 mg/kg, GSE 25mg/kg and GSE 50 mg/kg respectively. Except Gr I rats, all rats were injected intraperitoneally with Cyclophosphamide (100mg/kg) on day 9th and 16th of drug treatment. The effects on various organ weights, rise in Haemagglutination titre to Sheep RBC Antigen, delayed type of hypersensitivity (DTH) response to Sheep RBC, percentage of neutrophil adhesion to nylon fibre and phagocytic index from carbon clearance test were evaluated. Humoral and cellular immunity were measured from HA titre and DTH response respectively. It has been observed that, GSE 50 mg/kg significantly increased the antibody titre, percentage neutrophil adhesion and phagocytic index in CP induced immunosuppressed rats. It also restored the CP induced changes in organ weights and the DTH response at 24 and 48 hours of antigen challenge. But these effects were not comparable to that of Levamisole. Our study shows that Gymnema sylvestre reduced the CP induced immunotoxicities and therefore, it could be a safe supplement to cyclophosphamide chemotherapy.
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Shetty, Aditya, Hagop M. Kantarjian, Richard E. Champlin, Gautam Borthakur, Talha Badar, Guillermo Garcia-Manero, Borje S. Andersson, et al. "Survivorship In AML - Outcomes Of Acute Myelogenous Leukemia (AML) Patients (pts) After Maintaining Complete Remission (CR) For At Least 3 Years." Blood 122, no. 21 (November 15, 2013): 3886. http://dx.doi.org/10.1182/blood.v122.21.3886.3886.
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Abstract Introduction Approximately 80% of younger patients and 50% of older patients with newly diagnosed AML achieve CR after induction chemotherapy. The majority of patients who achieve CR eventually relapse, with most relapsing within the first 3 years. Long-term outcomes in pts maintaining 1st CR for at least 3 years (AML survivors) remain largely unknown. The purpose of this study was to investigate long-term outcomes in this subset of pts. Methods We performed a chart review of pts with AML treated at our institution who achieved CR for at least 3 years after their initial chemotherapy ± allogeneic stem cell transplant (ASCT) to analyze their long-term outcomes. Results 1792 pts with AML were treated between 2000 and 2010 at our institution. 1081 (60%) pts achieved CR. Among them, 266 (25%; 15% of all treated) maintained 1st CR for at least 3 years. The 1st 200 pts are described in this analysis: 33 after ASCT and 167 after chemotherapy (chemo) alone. Median time to CR from initiation of induction chemotherapy was 34 days (range, 19-115) for pts who received ASCT and 28 days (17-104) for chemo only. Characteristics of AML survivor pts at time of diagnosis were as follows: hypertension (HTN) was present in 25% of the pts; cardiac disease in 7%; hypothyroidism in 5%; diabetes (DM) in 7%; depression in 6%; osteoporosis in 2%; chronic obstructive disease (COPD) or asthma in 4%. Median number of medications per pt at baseline was 1 (0-7). Relapses after maintaining CR for ≥3 years (i.e., late relapses) were noted in 12% of the pts: 9% of the pts treated with ASCT and 12% of pts with chemo alone. The median CR duration for those who relapsed was 4 years (3-10) and 4.8 years (3-12), respectively. At relapse, karyotype was different from the karyotype at the time of diagnosis in 47% of the cases: 100% after ASCT and 41% after chemo alone. Mutational status changes at relapse were noted in 31% of the pts. New Flt3 ITD mutations were the most common change, noted in 75% of pts who had a mutational status change. A 2nd complete remission (CR2) was achieved in 52% of pts, including 33% of pts that had received ASCT and 56% of pts treated with chemo alone. The median CR2 duration was 5 months and 10 months (3-30) respectively. The median survival after relapse was 13 months (1 to 42). Four pts with relapsed disease who initially were treated with chemo only underwent ASCT; no patient received a 2nd ASCT. New medical problems that were present at the 3 year mark included: HTN in 10% of pts; cardiac disease in 4%; hypothyroidism in 4%; depression in 4%; renal insufficiency in 3%; pulmonary disease in 2%; DM in 3%; hematological disorders, including anemia, thrombocytopenia, monoclonal gammopathy of undetermined signigicance (MGUS), systemic mastocytosis & Waldenstorm’s macroglobulinemia, in 5%. Pulmonary disorders (e.g., bronchiolitis obliterans and COPD) occurred in 6% of pts who underwent ASCT and 2% of pts who treated with chemo alone. Renal insufficiency was noted in 9% of pts who underwent ASCT and in 2% of pts treated with chemo alone. The median number of medication per pt 3 yrs from initial CR was 3 (range, 0-11). New medical problems that developed at time of last follow up included: HTN in 12% of pts, cardiac disease in 6%, hypothyroidism in 5%, depression in 7%, renal insufficiency in 4%, pulmonary disease in 3%, DM in 5%, hematological disorders in 6%. Cardiac problems, including the development of coronary artery disease, myocardial infarction, congestive heart failure and arrhythmias were noted in 3% of pts who underwent ASCT and in 6% of pts treated with chemo alone. The median number of medications per pt at last follow up was 3 (0-14). Second malignancies occurred in 10% of pts. The most common 2nd malignancies were colorectal carcinoma, breast cancer, prostate cancer and lymphoma, each occurring in 2% of pts. At median follow up of 4.2 years (3.2-10.2) and 4.9 years (3.2-12) respectively, 94% and 80% of pts are alive. In descending order, the most common causes of death included AML relapse, second malignancy and myocardial infarction. Conclusion AML pts who achieved CR for at least 3 years have a low incidence of late relapses. New medical problems including heart disease and second malignancies may occur but most pts are still currently alive. AML pts who maintain 1st CR for at least 3 years require ongoing medical care and long-term surveillance. Disclosures: No relevant conflicts of interest to declare.
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Sebastian, Martin, Lotta von Boehmer, Alfred Zippelius, Frank Mayer, Martin Reck, Djordje Atanackovic, Michael Thomas, et al. "Messenger RNA vaccination and B-cell responses in NSCLC patients." Journal of Clinical Oncology 30, no. 15_suppl (May 20, 2012): 2573. http://dx.doi.org/10.1200/jco.2012.30.15_suppl.2573.
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2573^ Background: Vaccination with mRNA is a novel technology in cancer immunotherapy. CV9201 consists of self-adjuvanted mRNA molecules (RNActive) coding for five non small cell lung cancer (NSCLC)-associated tumor antigens (MAGE-C1, MAGE-C2, NY-ESO-1, BIRC5, 5T4). We report final results of a phase I/IIa trial of CV9201 in patients (pts.) with NSCLC. Methods: Pts. with stage IIIB/IV NSCLC with a response or stable disease after first-line chemotherapy or chemoradiation were eligible. Cohorts of 3 pts. were treated at three dose levels (400µg, 800µg and 1600µg CV9201) and observed for DLTs to select the highest tolerated dose for phase IIa. Primary endpoint was safety and tolerability; secondary endpoints were immune response, clinical efficacy and survival. Pts. received up to five vaccinations of CV9201 within 15 weeks. Antigen-specific immune responses against each of the 5 antigens were measured at baseline, and two weeks after the 3rd and 5th vaccination. Frequency of lymphocyte subsets and expression of activation and maturation markers were measured and retrospectively correlated with immunological and clinical parameters. Results: 46 pts. were included (9 phase I; 37 phase IIa); No DLTs occurred, and the 1600 µg dose was investigated in phase IIa. The most frequent related adverse events were mild to moderate injection site reactions and flu-like symptoms. 3 patients (7%) had potentially related grade 3 AEs (fatigue, injection site granuloma, asthma attack) and no related SAEs were reported. There were no objective responses. Data on PFS and survival will be presented. Antigen specific immune responses against at least one antigen were induced in 65% of pts. (39% cellular and 49% humoral). Consistently, a significant ≥2 fold increase of pre germinal center B cells (pGCB) was observed in 61% of pts. This increase of pGCB correlated significantly (p=0.0028) with increase of total CD4 effector T cells. Frequency of CD 4 T Reg cells did not increase during treatment. Conclusions: Vaccination with CV9201 has a favorable safety profile and induces T and B cell responses against all included antigens. Vaccine-induced increase of pGCB is a new finding and might be used as a biomarker in cancer immunotherapy.
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Udeani, George O., Karanjit Singh, Michael R. Mullane, and Thomas E. Lad. "Cisplatln Nephrotoxicity in a Patient with a Single Kidney." Annals of Pharmacotherapy 30, no. 7-8 (July 1996): 782–86. http://dx.doi.org/10.1177/106002809603000715.
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OBJECTIVE: To describe a patient with a single kidney who experienced cisplatin-associated nephrotoxicity. CASE SUMMARY: A 78-year-old African-American woman with squamous cell carcinoma of the base of her tongue (T4N2M1) was admitted electively to our institution for the first cycle of chemotherapy. Her past medical history was significant for a left nephrectomy secondary to well-differentiated papillary transitional cell carcinoma of the left renal pelvis, hypothyroidism, asthma, and coronary artery disease. Her blood urea nitrogen (BUN) was 27 mg/dL of urea, and serum creatinine was 1.2 mg/dL. On admission she was hydrated adequately, and was treated with an evening dose of cisplatin 100 mg/m2 (180 mg) in 250 mL of NaCl 0.9% solution in a 3-hour infusion, and a 5-day course of fluorouracil 1000 mg/m2 (1800 mg) in a 24-hour infusion. Serum creatinine and BUN concentrations following cisplatin administration were 1.1 mg/dL and 8 mg/dL, respectively. Four days after cisplatin therapy, a decline in renal function was observed, with an increase in serum creatinine and BUN concentrations to 4.0 mg/dL and 31 mg/dL, respectively. These tests remained elevated throughout her hospitalization. With hemodialysis treatments a resolution in altered mental status was observed; however, her chronic renal failure persisted. She was subsequently discharged and followed in the outpatient renal, geriatric, and oncology clinics. DISCUSSION: Cisplatin is a principal chemotherapeutic agent used in the treatment of a variety of solid tumors. Nephrotoxicity is a major complication associated with this compound. Although many clinicians believe that cisplatin nephrotoxicity is unlikely to occur in patients with a single kidney, recent reports have suggested otherwise. The physiologic changes of the aging kidney are such that they should foster cisplatin clearance rather than expose the kidney to the drug's nephrotoxic potential. In addition, evening administration of cisplatin is thought to minimize nephrotoxicity. We describe a 78-year-old woman with a single kidney who developed nephrotoxicity following a single evening dose of cisplatin. Details of the patient's history and cisplatin-associated complication and therapy are discussed. CONCLUSIONS: Cisplatin circadian rhythmic pharmacotherapy to minimize cisplatin toxicity in patients with a single kidney appears to be controversial and needs further evaluation.
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Landry, Madeleine, Amanda Pluntze, and Kimberly Shepard. "Abstract 1736: Local treatment of lung cancer by inhaled monoclonal antibodies: A pre-feasibility screening approach for spray drying." Cancer Research 82, no. 12_Supplement (June 15, 2022): 1736. http://dx.doi.org/10.1158/1538-7445.am2022-1736.
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Abstract Local treatment of asthma and COPD by inhaled therapies has been standard of care for decades. A similar approach for lung cancer treatment could bring many benefits to the patient, including ease of administration, non-invasiveness, and potential for reduced side effects. Spray drying is a versatile, scalable manufacturing technique used to engineer therapies for delivery to the lung by dry powder inhaler. It is applicable to nearly all classes of molecules, including RNA, small molecules and proteins. Spray dried inhalation powders eliminate the need for cold chain storage, and can improve product shelf life compared with liquid formulations, improving access for developing nations and rural populations. Recently, inhaled delivery for a VEGF inhibitor, bevacizumab, has shown in preclinical studies to reduce tumor burden in rats at 1/10th the dose of injected bevacizumab, when combined with chemotherapy. To enable the next generation of inhaled monoclonal antibody (mAb) therapies by spray drying, mAb structural integrity is key. Spray dried materials undergo thermal and shear stresses, which can damage delicate mAbs. Herein we identified a set of analytical tests to evaluate the upper limits of heat and shear mAbs can withstand during spray drying. We exposed five cancer-relevant, FDA-approved mAbs to varying heat and shear stress then characterized changes to primary (1°), secondary (2°), and tertiary (3°) structure and binding activity indicative of degradation. Using the following analytical techniques we detected graduations of degradation: capillary electrophoresis-isoelectric focusing (1°), Fourier transform infrared spectroscopy (2°), Raman spectroscopy (2°), size exclusion chromatography (3°), absorbance and fluorescence spectroscopy (3°), dynamic light scattering (3°), multi-cell differential scanning calorimetry (3°), SDS-PAGE (3°), and binding activity ELISAs. Using these techniques, we developed a materials-sparing protocol to first assess whether an antibody is a candidate for spray drying, and second, to identify ideal process conditions for mAb spraying drying success. This approach will help to accelerate the development of inhaled protein therapies for lung cancer and other lung diseases. Citation Format: Madeleine Landry, Amanda Pluntze, Kimberly Shepard. Local treatment of lung cancer by inhaled monoclonal antibodies: A pre-feasibility screening approach for spray drying [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1736.
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Frezzato, Federica, Flavia Raggi, Filippo Severin, Veronica Martini, Valentina Trimarco, Leonardo Martinello, Marco Pizzi, et al. "HSP70-HSF1 Interplays Has a Role in the Pathogenesis of Chronic Lymphocytic Leukemia and Is a Druggable Target." Blood 128, no. 22 (December 2, 2016): 4368. http://dx.doi.org/10.1182/blood.v128.22.4368.4368.
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Abstract INTRODUCTION We recently found that the Heat Shock Protein of 70kDa (HSP70), an ATP-dependent chaperone that is induced by cellular stress and protects cells against various apoptotic stimuli, was particularly overexpressed in neoplastic B cells from Chronic Lymphocytic Leukemia (CLL) vs normal B lymphocytes. HSP70 responds to a wide variety of physiological and environmental stress signals, thus allowing cells to survive to lethal conditions. The primary responsible for the transcription of HSP70 is the heat shock factor 1 (HSF1), being the major regulator of HSP70 expression. In response to stress, HSF1 becomes phosphorylated, forms homotrimers, binds DNA and activates heat shock gene transcription. Considering that the search for molecules involved in the apoptosis resistance and increased survival of B cells from CLL is still ongoing, with this as a background, we were aimed at studying and targeting HSP70 or players related to it (i.e. HSF1) in view of their clinical, prognostic and therapeutical relevance in CLL. METHODS HSP70/HSF1 axis was analysed in freshly isolated leukemic B cells from CLL patients. Expression levels of HSP70, HSF1 and HSF1-Ser326 were assessed by Western blotting analysis with specific antibodies and the obtained expression data have been correlated with clinical features of the patients. HSP70 subcellular localization has been determined by confocal microscopy and cell fractionation. HSP70 expression and localization was also assessed by immunohistochemistry in lymph nodes from CLL patients. Leukemic B cells from 15 CLL therapy-free patients were treated with different concentrations of: i) Zafirlukast, an oral leukotriene receptor antagonist used to prevent asthma symptoms and acting also as HSP70 inhibitor and ii) Fisetin, a dietary flavonoid acting as anti-inflammatory and anti-carcinogen, that inhibits HSF1 activity through the block of its binding to the HSP70 promoter. Apoptosis induction in CLL cells was evaluated by Annexin V/Propidium Iodide flow cytometry test and by the presence of cleaved PARP observed in Western blotting. RESULTS We found that HSP70 and HSF1 proteins were overexpressed in leukemic vs normal B cells and correlated to poor prognosis. In particular, IGHV unmutated or ZAP70 positive patients presented higher levels of HSP70 and HSF1 with respect to patients with a favorable prognosis. Moreover, the two proteins presented a positive correlation (p<0.0001, r=0.84; Pearson's correlation) thus hypothesizing a positive loop feedback for their expression. We found that, in CLL, HSF1 was constitutively phosphorylated at activatory Ser326, thus being positively regulated, in a large part of our patients. In addition, patients presenting a higher phosphorylation of HSF1 at Ser326 were mostly ZAP70 positive patients. We also observed an abnormal constitutive nuclear localization of HSP70 in leukemic cells. On the basis of these results and the pro-survival role played by HSP70 and HSF1, we analyzed the effects of their inhibition in leukemic cells of our patients by using two inhibitors of this axis, Zafirlukast and Fisetin. Both inhibitors have been proven to be effective in inducing a dose-dependent cell apoptosis in CLL B cells. CONCLUSIONS HSP70 overexpression is involved in a diminished response to treatment by promoting the adaptation of tumor cells to changes (i.e. toxic conditions) currently induced by chemotherapy thus revealing critical roles for HSP70 in cancer initiation and progression. It has been shown that HSP70 depletion results in an increased sensitivity to chemotherapy. For this reason, and considering its prognostic implications and functional role in cancers, including CLL, HSP70 represents an interesting target for antileukemic therapies. In this context, our results suggest: i) an involvement of HSP70/HSF1 axis in the pathogenesis of CLL; ii) an input for further studies that consider the possible involvement of ZAP70 in HSP70/HSF1 axis in CLL; iii) the putative usage of Zafirlukast, which is a drug already available for clinical use and in the targeting of HSF1 in CLL. Disclosures No relevant conflicts of interest to declare.
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Zarghamravanbakhsh, Paria, and Agustin Busta. "ODP290 A Rare Case of Hypopituitarism Secondary to Radiation Therapy for Nasopharyngeal Carcinoma." Journal of the Endocrine Society 6, Supplement_1 (November 1, 2022): A481—A482. http://dx.doi.org/10.1210/jendso/bvac150.1000.
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Abstract Radiation therapy with or without chemotherapy remains a mainstay of treatment for nasopharyngeal carcinomas. Radiation can cause neurological complications such as cranial nerve palsies, and brachial plexopathy as well as non-neurological complications including endocrinopathies like primary hypothyroidism and hypopituitarism. We describe a 30-year-old male with a diagnosis of nasopharyngeal carcinoma who presented to our clinic in June 2021 with low energy level, occasional headache,light-headedness, and poor balance. He received chemo and radiation treatment in 2014 that led to the diagnosis of pituitary hormone deficiency. He also reported erectile dysfunction and decreased libido. His history is remarkable formononucleosis, asthma, and bone fracture in high school while playing football. He developed subsequent hypothyroidism in 2016 and taking Levothyroxine 100 mcg daily since 2016. The patientwas diagnosed with hypogonadism in 2018 and receiving testosterone cypionate injection every 3 weeks. Patient diagnosis of hypothyroidism and hypogonadism prompted to initiate a hypopituitarism workup which lead us to find growth hormone deficiency. Laboratory workup showed low Total Testosterone 43.1 ng/dl (normal range(NR): 264-916), FSH <0.3 IU/L (NR: 1.5-12.4), low IGF-1 56 ng/dl(NR: 83-246), LH <0.3 IU/L(NR: 1.7-8.6),TSH 0.23 uIU/ml(NR: 0.27-4.2), Prolactin Undiluted 55.6,Diluted 49.8 ng/ml(NR: 4.1-18.4), SHBG 86. 0 nmol/L(NR: 16.5-55.9), Normal Free T4 1.4 ng/dl(NR: 0.9-1.8), Free T3 2. 07 pg/ml(NR: 1.8-4.6). Thyroid Antibodies were negative. ACTH-ESO 10 pg/ml(NR: 6-48) and normal Cortisol PM were 4. 0 Ug/dl (NR: 2.7-10.5). We found that he has growth hormone deficiency. We are currently implementing growth hormone supplementation treatment. The patient has been restarted on testosterone injections. Repeated TFTs showed Free T4 0.6 ng/dl, Free T3 1.78 pg/ml and TSH 2.30 uIU/ml. Levothyroxine was increased to 125 mcg daily. This case showed the importance of considering endocrinopathies as late complications of radiation therapy fornasopharyngeal carcinomas. In a cohort study by Tuan et al, primary hypothyroidism and hypopituitarism was reported(Incident rate of 13% and 6% accordingly). Previous studies showed somatotropic axis is the most vulnerable to radiation damage and after radiation, patients developed growth hormone deficiency, adrenal insufficiency, hypogonadism, and thyroid disorders. This case is unique considering that the patient was initially diagnosed with hypothyroidism subsequently hypogonadism and growth hormone deficiency diagnosed years later. Radiation can affect pituitary function. Hypopituitarism can be a late complication of radiation therapy in patients with nasopharyngeal carcinoma. Complete pituitary workup are advised to ensure timely diagnosis and early hormone replacement therapy in these patients. Our case will be helpful to other clinicians for diagnosis and management of endocrinopathies secondary to radiation therapy. Presentation: No date and time listed
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Mamedov, M. N., I. V. Druk, E. A. Turusheva, E. Yu Eremina, T. E. Morozova, B. G. Iskenderov, A. N. Sapozhnikov, S. I. Drozdetsky, and N. G. Badalov. "Behavioral risk factors and clinical course of cardiovascular diseases and other noncommunicable diseases during quarantine in various regions of Russia." Russian Journal of Cardiology 26, no. 9 (October 19, 2021): 4670. http://dx.doi.org/10.15829/1560-4071-2021-4670.
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Aim. To assess the behavioral risk factors and the clinical course of cardiovascular diseases (CVDs) and other noncommunicable diseases (NCDs) during quarantine in various regions of Russia.Material and methods. This multicenter cohort cross-sectional study included 205 men and women from 6 Russian cities. Further, 4 of them (Saransk, Nizhny Novgorod, Penza, Ulyanovsk) were combined into one group — the Volga region. The study included men and women aged 30-69 years with one or more NCDs (hypertension, coronary artery disease with or without myocardial infarction, type 2 diabetes, chronic obstructive pulmonary disease/asthma and cancer in patients receiving chemotherapy and/or radiation therapy) who were self-isolated during coronavirus disease 2019 (COVID-19) pandemic. For all patients, a questionnaire was used, which included socio-demographic parameters, behavioral risk factors, status of the underlying disease, incidence of COVID-19 and its complications. Self-assessment of the state of health was carried out using the European Quality of Life Questionnaire.Results. In every third Muscovite, the intensity of physical activity decreased, and in the groups of patients from Omsk and the Volga region, it was 45% and 43%, respectively. An increase in meal frequency and an impairment of eating habits in Moscow and Omsk was noted in 18,2% and 18,7% of participants, while in Volga region subjects, these parameters were 2 times higher (42,4%). At the same time, no significant changes of alcohol consumption and smoking was revealed in the cohorts. Hypertensive crises during a pandemic were noted in all three subgroups, but more of them were recorded in the Volga region — in every third patient (p< 0,05 compared to Moscow), in the Omsk group — in every fourth patient, and among Muscovites — no more than 5%. Clinical deterioration in patients with angina was noted in 15% of cases, while the smallest number was noted in Omsk subjects (5,3%), three times less than in other subgroups. Changes in intensity and regimen of hypoglycemic therapy were noted in patients from Omsk, while 30% of them (p< 0,05 compared with the Volga region) increased the doses of medications taken. Chronic obstructive pulmonary disease was registered in the group with the largest number of Volga region patients — 14,1% (p< 0,05 compared to Omsk), while 17% of patients in this group increased the dose of drugs. Any cancer was recorded in 13,6% of Muscovites, while in the other two groups — about 5%. The largest number of patients from the Volga region noted a health decline over the past year (30,8%), while every fifth patient from Omsk (19,6%) and 13,6% of Muscovites reported health changes.Conclusion. During quarantine and self-isolation, changes in dietary habits and physical activity decline were noted among patients with NCDs, while alcohol consumption and smoking remained practically unchanged. The change in clinical status was characterized by an increase in hypertensive crisis incidence, an increase in doses of antihypertensive and hypoglycemic medication. Depending on the region, the health decline was noted by 13-31% of patients with NCDs.
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Muro, Kei, Satoru Iwasa, Naotoshi Sugimoto, Hisato Kawakami, Takashi Oshima, Kensei Yamaguchi, Kaori Hino, et al. "Gastric cancer (GC) cohort of a phase 2 trial of E7389-LF (liposomal formulation of eribulin) in combination with nivolumab." Journal of Clinical Oncology 41, no. 4_suppl (February 1, 2023): 339. http://dx.doi.org/10.1200/jco.2023.41.4_suppl.339.
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339 Background: Due to a lack of efficacy and long-term survival seen in previously-studied therapies, new therapies for pretreated advanced GC are warranted. E7389-LF is a new formulation that uses liposomes to encapsulate eribulin; this is anticipated to improve eribulin concentration in tumor tissues. E7389-LF and nivolumab have both shown efficacy as monotherapy in pretreated GC. E7389-LF may also synergize well with PD-1 inhibitors by acting as a cytotoxic therapy and by modulating the tumor microenvironment. Methods: Patients (pts) with unresectable and measurable GC, esophageal cancer, or small cell lung cancer who were previously treated with 1 (2 for GC) chemotherapy regimens were enrolled in the phase 2 part of Study 120 and treated with E7389-LF 2.1 mg/m2 plus nivolumab 360 mg every 3 weeks (Q3W). In the GC cohort, pts had to show disease progression from combination therapy including a platinum drug + fluoropyrimidine (1st-line therapy) and a taxane-containing regimen (2nd-line therapy). The primary objective of the phase 2 part was to evaluate the objective response rate (ORR); secondary objectives included safety, progression-free survival (PFS), and pharmacokinetics. Other efficacy (including overall survival [OS]) and biomarker objectives were exploratory. Tumor responses were assessed by the investigators per RECIST v1.1. Results: 31 GC pts were included; median age was 63 years; 18 pts were male, 13 were female. By the data cutoff date (May 31, 2022), 29 pts discontinued (26 due to disease progression, 3 due to adverse events). 8 Pts had a partial response (PR); the ORR was 25.8% (95% CI 11.9–44.6). The median PFS was 2.69 months (95% CI 1.91–2.99). The median OS was 7.85 months (95% CI 4.47–not estimable). The 6-month OS rate was 61.3%; the 9-month OS rate was 44.7%. 30 Pts had ≥1 treatment-related TEAE, most commonly neutropenia (n = 24); 25 pts had at least 1 grade ≥3 treatment-related TEAE, most commonly neutropenia (n = 22). 16 Pts had ≥1 TEAE resulting in dose reduction of E7389-LF. 4 Pts had ≥1 TEAE resulting in withdrawal of E7389-LF or nivolumab, including asthma, cerebral hemorrhage, decreased appetite, pulmonary edema, and upper gastrointestinal hemorrhage (each n = 1). 29 Pts had an evaluable PD-L1 combined positive score (CPS); 5 of 20 pts (25.0%) with a CPS of < 5 and 2 of 9 (22.2%) with a CPS of ≥5 had a PR. Increases in pharmacodynamic markers including vasculature-related markers were observed; antitumor immunity was observed per changes in interferon gamma (IFNγ) and IFNγ-related markers. Conclusions: E7389-LF 2.1 mg/m2 in combination with nivolumab 360 mg Q3W had promising efficacy for pretreated GC, as evidenced by the notable ORR of 25.8% as well as by PFS and OS. No new safety signals were identified for this combination. Biomarker changes suggested vascular remodeling activity and enhancement of antitumor immunity via IFNγ signaling. Clinical trial information: NCT04078295 .
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Ostronoff, Fabiana, Mauricio Ostronoff, ANA Patricia Souto Maior, Rodolfo Calixto, Monique Martins, Mariana Coutinho, Alexandre Sucupira, Luis Fabio Botelho, and Rodrigo Florencio. "GCSF-Primed Allo-BMT Following Reduced Intensity Conditioning Regimen In Children with AML- Good Outcome In Patients In 1 st Complete Remission with Rapid Neutrophil Engraftment and Low Incidence of Chronic Gvhd." Blood 116, no. 21 (November 19, 2010): 4566. http://dx.doi.org/10.1182/blood.v116.21.4566.4566.
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Abstract Abstract 4566 There are few data on reduced intensity conditioning regimen in children with AML and no data for GCSF-primed BMT in this patient population. The related donors for these patients are commonly children as well and the peripheral blood stem cells collection is not often indicated. Primed-GCSF bone marrow harvest yields a higher number of CD34+ cells and a lower number of lymphocytes when compared to PBSCT resulting in faster neutrophil recovery and lower rate of chronic GVHD. From 2003 to 2009, we performed 12 GCSF-primed BMT in children with AML in our center median age 8 y (2-12); 10‰, 2 S; 8 pts in first CR (1 pt with AML 2ary to ALL-T treatment; 1 AML M7; 1 induction failure) and 04 pts with ≥ 2nd CR. FAB classification: 7 patients had AML M2; 2, AML M4; 1, AML-M5; 2, AML M7). These patients were not eligible for myeloablative SCT due to aspergilosis (4 patients), hepato-splenic abscess due to candidia (1 patient), recent sepsis due to Candida 2 pts, giant hamartoma causing restrictive pulmonary disease, severe asthma (1 patient), elevated transaminitis (greater than 5 times of the upper normal limit) due to recent multiple chemotherapies (2 patients), recent treatments with myeolosuppresive chemotherapies greater than 4 cycles complicated by recent infection (2 patients). The protocol was approved by our institutional review board and informed consent was obtained from each patient and donor and or their guardians. Conditioning consisted of fludarabine and TBI in 2 patients; busulfan 4mg/kg/day (day -5 and day -4) and fludarabine 30 mg/m2/day (from day-7 to day -2) in 9 patients. Three of these patients also received Ara-C 1g/m2 (day-5 to day -2). One patient undergoing unrelated donor BMT was conditioned with busulfan 4mg/kg/day (day -5 and day -4) and fludarabine 30 mg/m2/day (from day-7 to day -2) and ATG 10mg/kg/day (day -4 to day -1). GVHD prophylaxis consisted of CSA 5mg/kg/day orally from day -1 to day +90 and MMF 45mg/kg/day orally until day +30. The donors received G-CSF 5 μ g/kg/d subcutaneously for five days (day –4 to day 0) prior to harvest the bone marrow. The median age of the related donors was 9 years (range, 4 to 18 years). The stem cells harvest from the unrelated donor was not primed with GCSF. The median CD34+, CD3+ and CD8+ cell counts collected were respectively 3.5×106 cells/kg (2.5 - 5.0), 32 ×106 cells/kg (29 - 59) and 13×106 cells/kg (12- 25). All patients received GCSF 10 micrograms/kg/day SC from day +1 until neutrophil engraftment. Only 8/12 pts had neutrophil counts ≤ 500/mm3 for a short interval: median 3 days (2-8). There were no infectious complications and all CMV antigenemias were negative. The transfusion requirement was low for all patients. One patient rejected the graft on day+30 and 3 patients had mix chimerism on day +30 and relapsed few weeks later. All the other patients had complete chimerism on day +30 and continue to have stable complete chimerism thereafter. Grade >=II acute GVHD occurred in 2 patients (16.5%). Only one patient who underwent unrelated donor transplantation had steroid-resistant GVHD which responded to alemtuzumab. There were no deaths related to the transplant. Five patients died due to relapsed leukemia 2,3,3,4 and 19 months after the transplant the savage therapy was very difficult: 2 of these pts had chemotherapy refractory leukemia, 2 pts were refractory to conventional BMT and one pt had aspergilosis after the second conventional BMT. This pt had a previous history of aspergilosis. Seven of the 12 patients (58%) are alive and in complete remission of their leukemia 1,2,3,3,4,6 and 7 years after BMT. None of the patients developed extensive chronic GVHD. Among the patients who survived, there were5/7 (71%) is first CR including one case of secondary AML, the case of AML-M7 and one pt who had failed induction chemotherapy. RIC in children who are not eligible for myeloablative SCT can be well tolerated and successful specially in patients who are in first complete remission. In addition, primed-GCSF BMT can be a good strategy to achieve rapid neutrophil engraftment with low rate of chronic GVHD. Disclosures: No relevant conflicts of interest to declare.
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王宥勻, 王宥勻, 楊美英 Yu-Yun Wang, and 曾芃廩 Mei-Yin Yang. "一位罹患肺腺癌的末期腎病變病人首次接受血液透析之護理經驗." 臺灣腎臟護理學會雜誌 20, no. 2 (June 2022): 015–28. http://dx.doi.org/10.53106/172674042022062002002.
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<p>本文為一位罹患肺腺癌的末期腎病變病人，面臨雙重重大疾病治療的壓力下，接受初次化學及血液透析治療的護理經驗。護理期間於2018年7月31日至9月30日，運用Gordon十一項健康功能型態為評估工具，透過直接照護及觀察等方式蒐集資料，確認病人有體液容積過量、營養失衡及無望感等健康問題，透過回覆示教及教導病人水分控制技巧，改善因體液容積過量所致呼吸喘的症狀；經偕同營養師制定飲食治療計劃，改善因化學治療副作用導致的營養失衡；藉由跨團隊照護、家人及病友支持，成功地使病人適時表達因雙重重大疾病所產生的經濟壓力困境與對未來生活價值的無望感。冀望將此照護經驗分享，讓同性質病人能坦然面對生命逆境，順利進入化學及血液透析治療，早日回歸職場。</p> <p> </p><p>This article was about a patient with end-stage renal disease and lung adenocarcinoma and then she received nursing experience of initial chemical and hemodialysis . The author cared for such a patient from July 31, 2018 to september 30, 2018, Using Gordon’s 11 functional appraisals and both observation and discussion, the following patient’s care issues were identified ,including fluid overload , malnutrition, hopelessness .With these,we can teach the patient skills to control water,and improve the symptoms of asthma caused by fluid overload.Also,we can formulate a diet therapy plan with a dietitian to improve the nutritional imbalance caused by the side effects of chemotherapy. With cross-team care, family and patient support,we can successfully make the patient talk about their difficulties cause by double major diseases in a timely manner,and hopeless economical pressure . I hope to share this care experience and recommend it to the case care seminars of related units.With this, patients of the same nature can face life’s adversity calmly and smoothly.Then,patients will be willing to choose the chemical and hemodialysis treatments, and return to the workplace as soon as possible.</p> <p> </p>