Targeting neutrophils in inflammatory bowel disease: revisiting the role of adsorptive granulocyte and monocyte apheresis
Introduction: Inflammatory bowel disease (IBD) is a chronic immune-mediated disease of the gastrointestinal tract comprising Crohn’s disease (CD) and ulcerative colitis (UC). While any part of the digestive tract can be affected in CD, mucosal inflammation in UC is limited to the colon. Differences and similarities between the two conditions are reflected by their pathophysiology. Areas covered: An overview of immunological aspects, pharmacological management, and biomarkers of IBD is provided. The role of adsorptive granulocyte and monocyte apheresis (GMA) is reviewed including its primary and secondary effects on the immune system, as well as clinical studies in IBD (mainly UC), and potential biomarkers for adsorptive GMA. Expert opinion: In UC, adsorptive GMA with Adacolumn (Adacolumn®, JIMRO Co., Ltd. Takasaki, Gunma, Japan) selectively depletes elevated myeloid lineage leukocytes and has a range of beneficial secondary immune effects. Adsorptive GMA is a safe and effective non-pharmacological treatment option for UC. Pilot studies have reported promising results for adsorptive GMA in combination with biological agents, although larger studies are required. Fecal calprotectin concentrations, neutrophil counts in histological samples and/or the neutrophil/lymphocyte ratio in peripheral blood may prove to be useful biomarkers for predicting GMA effectiveness in the future.
Granulocytapheresis in ulcerative colitis (in Spanish)
Gerardo Prieto Bozano an. pedatr. contin.2012;10(5):286-9
- Existen 2 dispositivos de granulocitoféresis: Cellsorba® (fibras de poliéster no tejidas), que fija granulocitos y linfocitos, y Adacolumn® (acetato de celulosa) que fija selectivamente granulocitos y monocitos.
- Además de retirar leucocitos activados, la aféresis produce incremento del número de granulocitos CD10-negativos (inmaduros), disminución de citocinas proinflamatorias (factor de necrosis tumoral alfa [TNF-α], interleucina [IL-6],IL-8 e IL-1β) e incremento de citocinas inhibitorias (IL-1, IL-10)
- La granulocitoféresis es un método razonablemente eficaz y seguro para obtener la remisión en niños con colitis ulcerosa corticodependiente o resistente, sobre todo en pacientes en el primer episodio, en enfermedad de corta evolución y en aquellos que no han recibido esteroides
- El procedimiento requiere 2 accesos venosos de buen flujo. La pauta más habitual de tratamiento consiste en 1–2 sesiones semanales de 60min a un flujo de 30ml/min, hasta un total de 5–10 sesiones
Security of therapeutic apheresis in pediatrics. prospective study during 2018 in 171 apheresis sessions
Víctor López Baez, Pedro Arango Sancho, Yolanda Calzada Baños, Elena Codina Sampera, Ana Vinuesa Jaca, Lina Hernández Zúñiga, Álvaro Madrid Aris, Nephrology Dialysis Transplantation, Volume 35, Issue Supplement_3
The apheresis techniques in pediatrics had been presented with few complications in our center, none derived from vascular access, anticoagulation, infections or adverse effects due to use of replacement fluid. The training of medical and nursing staff is essential to identify risk situations. The use of protocols and international guidelines ensure safety in pediatrics.
Recommendations for Therapeutic Apheresis by the Section “Preparative and Therapeutic Hemapheresis” of the German Society for Transfusion Medicine and Immunohematology
The section “Preparative and Therapeutic Hemapheresis” of the German Society for Transfusion Medicine and Immunohematology (DGTI) has reviewed the actual literature and updated techniques and indications for evidence-based use of therapeutic apheresis in human disease. The recommendations are mostly in line with the “Guidelines on the Use of Therapeutic Apheresis in Clinical Practice” published by the Writing Committee of the American Society for Apheresis (ASFA) and have been conducted by experts from the DACH (Germany, Austria, Switzerland) region.
LS2-02 Tips for ensuring vascular access and maintaining extracorporeal circulation in pediatric blood purification therapy
poster at ISFA 2019 pag 164-165
Ensuring reliable vascular access (VA) and maintaining stable extracorporeal circulation are the most basic aspects of blood purification therapy (BPT). In children and neonates, specific tips could be helpful for BPT.
VA guidelines were published in 2011 and management methods have been unified. To ensure VA, it is necessary to determine a suitable placement site and catheter size (diameter and length), adjust the catheter tip position, and manage the catheters appropriately. It is common to use dialysis catheters for BPT, placing them in the central and peripheral veins. In neonates, the umbilical vein could also be one of the options, and central venous catheters and peripheral vein catheters could be used for BPT. In order to maintain stable extracorporeal circulation, it is necessary to maintain sufficient intravascular volume and blood pressure, set appropriate blood flow rates, and adjust the type and amount of anticoagulant. In children who cannot cooperate,
sedation management and catheter fixation should be performed to stabilize extracorporeal circulation.
There are also tips specialized for each disease state. In neonates, there is a high risk of intracranial hemorrhage and nafamostat mesylate is often used as an anticoagulant. In addition, it is necessary to increase the dose of anticoagulant or administer it from two places in the circuits. In patients with severe inflammatory bowel diseases, intestinal bleeding continues despite increased clotting function and hypovolemia is common. Heparin and nafamostat mesylate are chosen as anticoagulants. During BPT, monitoring activated clotting time, administering minimal anticoagulants, and administering transfusion and fluid load are useful methods to maintain stable extracorporeal circulation. BPT might be a powerful therapeutic tool for children as well as adults, ensuring reliable VA and maintaining stable extracorporeal circulation.
Management of Paediatric Ulcerative Colitis, Part 1: Ambulatory Care-An Evidence-based Guideline From European Crohn’s and Colitis Organization and European Society of Paediatric Gastroenterology, Hepatology and Nutrition
Background: The contemporary management of ambulatory ulcerative colitis (UC) continues to be challenging with ∼20% of children needing a colectomy within childhood years. We thus aimed to standardize daily treatment of pediatric UC and inflammatory bowel diseases (IBD)-unclassified through detailed recommendations and practice points. Methods: These guidelines are a joint effort of the European Crohn’s and Colitis Organization (ECCO) and the Paediatric IBD Porto group of European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN). An extensive literature search with subsequent evidence appraisal using robust methodology was performed before 2 face-to-face meetings. All 40 included recommendations and 86 practice points were endorsed by 43 experts in Paediatric IBD with at least an 88% consensus rate. Results: These guidelines discuss how to optimize the use of mesalamine (including topical), systemic and locally active steroids, thiopurines and, for more severe disease, biologics. The use of other emerging therapies and the role of surgery are also covered. Algorithms are provided to aid therapeutic decision-making based on clinical assessment and the Paediatric UC Activity Index (PUCAI). Advice on contemporary therapeutic targets incorporating the use of calprotectin and the role of therapeutic drug monitoring are presented, as well as other management considerations around pouchitis, extraintestinal manifestations, nutrition, growth, psychology, and transition. A brief section on disease classification using the PIBD-classes criteria and IBD-unclassified is also part of these guidelines. Conclusions: These guidelines provide a guide to clinicians managing children with UC and IBD-unclassified management to provide modern management strategies while maintaining vigilance around appropriate outcomes and safety issues.
Pediatric inflammatory bowel disease : clinical and immunological aspects on remission treatment
- Helena Rolandsdotter Published 2017 Medicine
Finally, we studied the immunological profile in blood at onset and in intestinal mucosa at onset and after GMA and EEN treatment. We conclude that an active approach is needed in the care of children with IBD to achieve and maintain remission. Our findings reveal that the children on IFX maintenance treatment were only in remission in 28% of the visits. The combination of GMA and mesalazine was found to be a safe and effective treatment in children with newly onset IBD. It seems plausible to speculate that the decreases in mucosal cytokines after the induction of remission may explain the good clinical result. Moreover, a change in the mucosal cytokine profile after induction of remission with EEN was observed. By investigating the chemokine receptors, we found a possible prognostic IBD marker, and by analyzing the cytokine profiles in mucosal biopsies, we have extended the knowledge of immunological phenotypes in children with IBD. Suggestions for the future Corticosteroid-free treatment alternatives must be explored and those currently in use must be optimized. To conclude, more and bigger studies are needed to explore the pathogenesis of IBD to determine new treatment alternatives.
Granulocitoaféresis en 2017. Puesta al día (Spanish)
Granulocyte apheresis is a procedure that allows the removal of different activated leukocyte populations and it also modifies some circulating inflammatory mediators. These effects, along with its immunomodulatory potential, make it an attractive therapeutic option in inflammatory bowel disease. Previous studies with this technique have had significant limitations, but recent data is emerging about the ideal clinical setting in which granulocyte apheresis should be indicated. Most of the evidence supports its use in conditions that are dependent or refractory to corticosteroids, especially when treatments with immunomodulators or biologics has failed and when it is necessary to reduce or avoid the use of systemic corticosteroids. Its excellent safety profile gives it a role in cases of comorbidity or risk in the use of immunosuppressive drugs or in paediatric patients. In this review, we provide an update on the role of granulocyte apheresis in inflammatory bowel disease.
Leukocytapheresis in pediatric patients with ulcerative colitis
Takeshi Tomomasa 1, Hitoshi Tajiri, Seiichi Kagimoto, Toshiaki Shimizu, Atsushi Yoden, Kosuke Ushijima, Keiichi Uchida, Hiroaki Kaneko, Daiki Abukawa, Mutsuko Konno, Shun-ichi Maisawa, Takao Kohsaka, Akio Kobayashi, Japanese Study Group for Pediatric Ulcerative Colitis J Pediatr Gastroenterol Nutr. 2011 Jul;53(1):34-9. doi: 10.1097/MPG.0b013e31821058bc.
Objective: Leukocytapheresis (LCAP) is a nonpharmacologic therapy that has recently been used to treat ulcerative colitis (UC). This multicenter open-label study prospectively assessed the efficacy and safety of LCAP in pediatric patients with UC. Patients and methods: Twenty-three patients ages 8 to 16 years with moderate (n = 19) to severe (n = 4) steroid-resistant UC were enrolled. One of 2 LCAP columns with different volumes (model EX and the half-volume model EI) was selected, according to body weight. LCAP was performed once per week for 5 consecutive weeks. Clinical and laboratory data were collected at predetermined time points. The primary endpoint was decreased stool frequency/hematochezia score, and secondary endpoints were clinical, laboratory, and endoscopic improvements. Results: The stool frequency/hematochezia score decreased significantly from 4.5 ± 1.2 before treatment to 1.6 ± 1.9 after the fifth treatment. Clinical parameters, including stool frequency, presence of visible blood, abdominal pain, and body temperature, were significantly improved. Fecal calprotectin decreased significantly. Endoscopic findings evaluated using Matts score also improved (P < 0.01). The steroid dose decreased from 1.1 ± 0.4 mg/kg before treatment to 0.8 ± 0.5 mg/kg after treatment. There were no significant differences in changes between the EX and EI columns. The incidence of adverse effects was 61%, although none was serious. The most common adverse effects were decreased hematocrit and hemoglobin concentration. Conclusions: The present study showed that LCAP was well tolerated in children with UC, mostly moderate, and was as effective as in adults. The types of pediatric patients best suited to LCAP remain to be determined.
Leukocytapheresis in a girl with severe ulcerative colitis refractory to corticosteroids, infliximab, and cyclosporine A
Although medical therapy remains the first-line treatment for UC, colectomy may be required for patients with severe medically refractory disease. Leukocytapheresis (LCAP) has been reported as a new line of therapy in
patients with UC. Only 2 pediatric case series, not including patients on immunosuppressive therapy or biologicals, treated with granulocytapheresis have been reported. The patient reported by us is the youngest to the best of our knowledge in which this LCAP technique was used . She had severe colitis refractory to corticosteroids, infliximab and yclosporine A. We were able to avoid colectomy and the procedure was well tolerated.
Contact UsFor more informationContact Us