scholarly journals Clinical Presentation and Management of a Dinutuximab Beta Extravasation in a Patient with Neuroblastoma

Children ◽  
2021 ◽  
Vol 8 (2) ◽  
pp. 91
Author(s):  
Michael Launspach ◽  
Marita Seif ◽  
Theresa M. Thole ◽  
Patrick Jesse ◽  
Joachim Schulz ◽  
...  
Keyword(s):  
High Risk ◽  
Neuroblastoma Cells ◽  
Drug Application ◽  
Immunocompromised Host ◽  
Laboratory Diagnostics ◽  
Chemotherapy Drugs ◽  
Reactive Protein ◽  
Intravenous Antibiotics ◽  
Inflammatory Toxicity ◽  
Bacterial Superinfection

Extravasation can present serious accidental complication of intravenous drug application. While monoclonal antibodies do not show the necrotic potential of cytotoxic chemotherapy drugs, considerable inflammatory toxicity can occur, necessitating standardized operating procedures for the management of their extravasation. Here, we report the clinical course and management of dinutuximab beta extravasation in a 3-year-old child. Dinutuximab beta is a chimeric monoclonal antibody targeting the GD2 disialoganglioside on the surface of neuroblastoma cells that has in recent years gained significant importance in the treatment of high-risk neuroblastoma, now contributing to both first- and second-line therapy protocols. The dinutuximab beta extravasation reported here occurred when the patient received the antibody cycle as a continuous infusion over a 10-day period after haploidentical stem cell transplantation for relapsed high-risk neuroblastoma. The extravasated dinutuximab beta caused local pain, swelling, and hyperemia accompanied by fever and an overall deterioration in the general condition. Laboratory diagnostics demonstrated an increase in C-reactive protein level and total white blood cell count. Clinical complication management consisted of intravenous fluid therapy, local dabbing with dimethyl sulfoxide (DMSO), analgesia with dipyrone, as well as application of intravenous antibiotics to prevent bacterial superinfection in the severely immunocompromised host. The patient considerably improved after six days with this treatment regimen and fully recovered by day 20.

scholarly journals GCT-25. INNOVATIVE, INTENSIVE IRRADIATION-AVOIDING/MINIMIZING CHEMOTHERAPY FOR HIGH-RISK PRIMARY CENTRAL NERVOUS SYSTEM (CNS) MIXED MALIGNANT GERM CELL TUMORS (HR-MMGCT): A PILOT STUDY AND PROPOSED MULTI-NATIONAL PROSPECTIVE TRIAL

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii333-iii333
Author(s):  
Jonathan L Finlay ◽  
Mohammad H Abu-Arja ◽  
Rolla Abu-Arja ◽  
Jeffery Auletta ◽  
Mohamed S AbdelBaki ◽  
...  
Keyword(s):  
High Risk ◽  
Induction Chemotherapy ◽  
Prospective Trial ◽  
Germ Cell Tumors ◽  
Brentuximab Vedotin ◽  
Pineal Region ◽  
Chemotherapy Drugs ◽  
Molecularly Targeted Agents ◽  
Risk Patients ◽  
Intensified Chemotherapy

Abstract BACKGROUND About one-third of children with primary CNS MMGCT experience incomplete responses to initial induction chemotherapy prior to irradiation, many of whom will subsequently relapse. Such high-risk patients are variably defined as having initial alpha-fetoprotein (AFP) elevations exceeding 1,000ng/mL, predominant histopathologies of malignant non-germinomatous GCT and incomplete responses to induction chemotherapy. Drugs targeting GCT-specific molecular markers have been identified for non-germinomatous GCT elements but have yet to be incorporated into prospective clinical trials. Four children with clearly identified HR-MMGCT characteristics have been treated on an innovative pilot regimen incorporating intensified chemotherapy and molecularly targeted agents, with avoidance or minimization of irradiation. METHODS Four children (two with pure suprasellar embryonal carcinoma (EC) - one with Down syndrome and the other with pre-diagnosis cognitive dysfunction; one with initial serum AFP exceeding 7,000ng/mL and yolk sac tumor (YST)+EC+Teratoma pathology; one with initial serum AFP exceeding 1,000ng/mL) were treated with 3 cycles of “standard” induction chemotherapy (ACNS1123), followed by 1–3 transplant cycles (thiotepa/carboplatin) each with complete radiographic and tumor marker responses. Two children with pure EC subsequently received six cycles of brentuximab-vedotin without irradiation and remain disease-free off therapy for 2–4 years. One child with YST+EC+Teratoma has subsequently received reduced dose craniospinal irradiation and pineal region boost, and will receive oral everolimus, erlotinib, palbocyclib and intravenous brentuximab-vedotin. The fourth child with YST+MT will commence everolimus, erlotinib and palbocyclib without irradiation. CONCLUSION This treatment strategy for HR-MMGCT patients provides preliminary tolerance and response data justifying extension to a multi-center trial.

scholarly journals Temporal Quantitative Proteomics Analysis of Neuroblastoma Cells Treated with Bovine Milk-Derived Extracellular Vesicles Highlights the Anti-Proliferative Properties of Milk-Derived Extracellular Vesicles

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 750
Author(s):  
Pamali Fonseka ◽  
Taeyoung Kang ◽  
Sing Chee ◽  
Sai V. Chitti ◽  
Rahul Sanwlani ◽  
...  
Keyword(s):  
High Risk ◽  
Extracellular Vesicles ◽  
Quantitative Proteomics ◽  
Cell Metabolism ◽  
Bovine Milk ◽  
Neuroblastoma Cells ◽  
Treatment Strategies ◽  
Treatment Resistance ◽  
Label Free ◽  
The Impact

Neuroblastoma (NBL) is a pediatric cancer that accounts for 15% of childhood cancer mortality. Amplification of the oncogene N-Myc occurs in 20% of NBL patients and is considered high risk as it correlates with aggressiveness, treatment resistance and poor prognosis. Even though the treatment strategies have improved in the recent years, the survival rate of high-risk NBL patients remain poor. Hence, it is crucial to explore new therapeutic avenues to sensitise NBL. Recently, bovine milk-derived extracellular vesicles (MEVs) have been proposed to contain anti-cancer properties. However, the impact of MEVs on NBL cells is not understood. In this study, we characterised MEVs using Western blotting, NTA and TEM. Importantly, treatment of NBL cells with MEVs decreased the proliferation and increased the sensitivity of NBL cells to doxorubicin. Temporal label-free quantitative proteomics of NBL cells highlighted the depletion of proteins involved in cell metabolism, cell growth and Wnt signalling upon treatment with MEVs. Furthermore, proteins implicated in cellular senescence and apoptosis were enriched in NBL cells treated with MEVs. For the first time, this study highlights the temporal proteomic profile that occurs in cancer cells upon MEVs treatment.

scholarly journals Periprocedural Peritonitis Prophylaxis: A Summary of the Microbiology and the Role of Systemic Antimicrobials

2021 ◽  
Vol 7 (2) ◽  
pp. 90-99
Author(s):  
Leon Hsueh ◽  
Susie L. Hu ◽  
Ankur D. Shah
Keyword(s):  
Peritoneal Dialysis ◽  
High Risk ◽  
Antibiotic Prophylaxis ◽  
Catheter Insertion ◽  
Antibiotic Regimen ◽  
Dental Procedures ◽  
Intravenous Antibiotics ◽  
Skin Flora ◽  
Potential Strategy

Background: Peritonitis is a leading complication of peritoneal dialysis (PD). One strategy that the International Society for Peritoneal Dialysis (ISPD) has used to help mitigate the morbidity and mortality associated with peritonitis is through prevention, including antibiotic prophylaxis utilization in high-risk situations. The aim of this study is to summarize our current understanding of postprocedural peritonitis and discuss the existing data behind periprocedural antibiotic prophylaxis, focusing primarily on PD catheter insertion, dental procedures, colonoscopies, upper endoscopies with gastrostomy, and gynecologic procedures. Summary: The ISPD currently recommends intravenous antibiotics prior to PD catheter insertion, colonoscopies, and invasive gynecologic procedures, though prophylaxis has only demonstrated benefit in a prospective, randomized control setting for PD catheter insertion. However, multiple retrospective studies exist that support the use of antibiotic prophylaxis for the other 2 procedures. No specific antibiotic regimen has been established as most optimal to prevent peritonitis for any of the 3 procedures. Antibiotic coverage should include the Enterobacteriaceae family, as well as Gram-positive organisms commonly found on the skin flora for PD catheter insertion, anaerobes for colonoscopies, and common organisms from the urogenital flora in gynecologic procedures. Additionally, the ISPD currently recommends oral amoxicillin prior to dental procedures. There is currently no ISPD recommendation to provide antibiotic prophylaxis prior to an upper endoscopy with or without gastrostomy, though this is a potential area for research. Key Messages: PD patients are at high risk for developing peritonitis after typical procedures. Antibiotic prophylaxis is a potential strategy that the ISPD utilizes to prevent these infections. However, further research needs to be done to determine the optimal antibiotic regimen.

scholarly journals VIP and PACAP analogs regulate therapeutic targets in high-risk neuroblastoma cells

Peptides ◽  
2016 ◽  
Vol 78 ◽  
pp. 30-41 ◽  
Author(s):  
Madryssa de Boisvilliers ◽  
Florian Perrin ◽  
Salima Hebache ◽  
Annie-Claire Balandre ◽  
Souheyla Bensalma ◽  
...  
Keyword(s):  
High Risk ◽  
Neuroblastoma Cells ◽  
Therapeutic Targets

scholarly journals Pharmacokinetics of 13-cis-Retinoic acid in high-risk neuroblastoma patients

2020 ◽  
Vol 19 (4) ◽  
pp. 20-31
Author(s):  
E. A. Litvin ◽  
D. T. Utalieva ◽  
D. Yu. Kachanov ◽  
A. V. Pshonkin ◽  
M. Ya. Yadgarov ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
High Risk ◽  
Medical Research ◽  
High Performance ◽  
Plasma Concentrations ◽  
Neuroblastoma Cells ◽  
Research Center ◽  
Therapeutic Drug ◽  
Pediatric Hematology ◽  
National Medical

13-cis-Retinoic acid is a differentiation agent for neuroblastoma cells and is a part of post-consolidation therapy for high-risk patients. The effectiveness of this therapeutic approach is currently under study. 26 patients with high-risk neuroblastoma treated at Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology were included in the study of 13-cis-Retinoic acid pharmacokinetics by high-performance liquid chromatography assay with ultraviolet detector depending on the method of administration of drug (swallowed capsules or opened capsules before administration). This study is supported by the Independent Ethics Committee and approved by the Academic Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. The current study showed that the therapeutic concentration of > 2 μM when taking 13-cis-Retinoic acid at a dose of 160 mg/m2/day was achieved in two groups, regardless of the method of drug administration. However, plasma concentrations of 13-cis-Retinoic acid at 4 hours after administration on the 14th day of therapy were higher in the group of patients who swallowed the capsules (4.1 ± 1.8 μM), compared to those who could not do it (1.9 ± 1.5 μM) (p = 0.022). The introduction into the clinical practice of therapeutic drug monitoring of 13-cis-retinoic acid in high-risk neuroblastoma patients with an assessment of peak concentration and dose adjustment of the following courses may be an important point in the attempt to optimize postconsolidation therapy and improve prognosis.

scholarly journals Anti-GD2 IgA kills tumors by neutrophils without antibody-associated pain in the preclinical treatment of high-risk neuroblastoma

2021 ◽  
Vol 9 (10) ◽  
pp. e003163
Author(s):  
Mitchell Evers ◽  
Marjolein Stip ◽  
Kaylee Keller ◽  
Hanneke Willemen ◽  
Maaike Nederend ◽  
...  
Keyword(s):  
High Risk ◽  
Sensory Neurons ◽  
Complement System ◽  
Severe Pain ◽  
Neuroblastoma Cells ◽  
Antibody Therapy ◽  
Preclinical Treatment ◽  
The Complement System

BackgroundThe addition of monoclonal antibody therapy against GD2 to the treatment of high-risk neuroblastoma led to improved responses in patients. Nevertheless, administration of GD2 antibodies against neuroblastoma is associated with therapy-limiting neuropathic pain. This severe pain is evoked at least partially through complement activation on GD2-expressing sensory neurons.MethodsTo reduce pain while maintaining antitumor activity, we have reformatted the approved GD2 antibody ch14.18 into the IgA1 isotype. This novel reformatted IgA is unable to activate the complement system but efficiently activates leukocytes through the FcαRI (CD89).ResultsIgA GD2 did not activate the complement system in vitro nor induced pain in mice. Importantly, neutrophil-mediated killing of neuroblastoma cells is enhanced with IgA in comparison to IgG, resulting in efficient tumoricidal capacity of the antibody in vitro and in vivo.ConclusionsOur results indicate that employing IgA GD2 as a novel isotype has two major benefits: it halts antibody-induced excruciating pain and improves neutrophil-mediated lysis of neuroblastoma. Thus, we postulate that patients with high-risk neuroblastoma would strongly benefit from IgA GD2 therapy.

scholarly journals Pyrexia of unknown origin associated with a non-infected vaginal shelf pessary

2020 ◽  
Vol 49 (6) ◽  
pp. 1110-1111
Author(s):  
Mathew Gilbert ◽  
Myra Laurenson ◽  
James Casson ◽  
Ali Alsawaf
Keyword(s):  
Unknown Origin ◽  
Additional Line ◽  
Pyrexia Of Unknown Origin ◽  
Reactive Protein ◽  
Source Of Infection ◽  
Vaginal Pessary ◽  
Intravenous Antibiotics ◽  
Chest X Ray ◽  
Urine Microscopy ◽  
Tomography Scan

Abstract An 82-year-old female was admitted with pyrexia and rigors. Bloods showed a raised C-reactive protein and she was commenced on empirical intravenous antibiotics. Chest X-ray, urine microscopy and computed tomography scan of the patient’s abdomen and pelvis did not demonstrate a source of infection, and blood cultures did not grow a microorganism. A collateral history was taken from the patient’s husband who raised concerns regarding her vaginal shelf pessary and it was therefore removed. Subsequently the patient’s fever subsided, her inflammatory markers improved and she was discharged 2 days later. We believe this is the first reported case of pyrexia secondary to a non-infected vaginal pessary, and may provide clinicians with an additional line of enquiry when presented with patients with pyrexia of unknown origin.

Sign in / Sign up

Export Citation Format

Share Document