Gerardo Prieto Bozano an. pedatr. contin.2012;10(5):286-9
Granulocytapheresis in ulcerative colitis (in Spanish)
- 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
The New Molecules Are Changing the Course of Pediatric Chronically Active Ulcerative Colitis: A Series of Pediatric Cases
Rafael Martín-Masot, MD, *Pilar Ortiz Pérez, MD, *Encarnación Torcuato Rubio, MD,
*Javier Blasco Alonso, PhD, *Marta Herrador López, †Carmen Gallego Fernández, PhD,
and *Víctor Manuel Navas-López, PhD, DOI: 10.1097/PG9.0000000000000100
Chronically active ulcerative colitis (UC) constitutes a challenge in an era where medical therapeutic options have increased while experience with colectomies has decreased. The change in the therapeutic paradigm of the disease means that patients with chronically active UC are being managed waiting to find their therapeutic target. We present 2 cases of children with chronically active UC who did not respond to intravenous steroids nor sequential therapy. A response was obtained with ustekinumab and tofacitinib, 2 drugs widely used in adults but still with little evidence in children. Highlighting the important role of patients and their families helped decision making, facilitating the work of the medical team. With multidisciplinary
management and close follow-up, they have been able to avoid surgery entering complete clinical remission.
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.
P356 Safety and effectiveness of granulocyte and monocyte adsorptive apheresis in paediatric patients with inflammatory bowel disease: a multi-centre cohort study
N Toita, H Tanaka, K Arai, H Shimizu, D Abukawa, T Kobayashi, N Yoshimura, S Tanida, E Hosoi, Journal of Crohn’s and Colitis, Volume 13, Issue Supplement_1, March 2019
Background: The usefulness of granulocyte and monocyte adsorptive apheresis (GMA) in paediatric patients with inflammatory bowel disease (IBD) has not been studied in depth. We investigated the safety and effectiveness of GMA in paediatric patients with IBD who participated in a post-marketing surveillance study referred to as the PARTICULAR study.
Methods: The PARTICULAR study was a retrospective, multi-centre cohort study that included patients with ulcerative colitis (UC) or Crohn’s disease (CD) who received GMA between November 2013 and March 2017. The study enrolled patients with at least one special situation, including paediatric, being elderly, with anaemia and concomitant treatment with multiple immunosuppressants. Patients aged >18 years were excluded from this study. The GMA was performed using Adacolumn® (JIMRO, Takasaki, Japan). Each patient underwent up to 11 GMA sessions. All adverse events (AEs) were recorded during the observation time interval. Any AE, for which the causality of the GMA could not be ruled out was classified as an adverse device effect (ADE). In addition, feasibility problems (FPs) during the operation of the GMA column were recorded. The effectiveness of GMA was assessed in UC patients with a partial Mayo (pMayo) score of ≥3. Remission was defined as a pMayo score of ≤2. Patients receiving concomitant treatment with infliximab, adalimumab or calcineurin inhibitors were excluded from the effectiveness assessment.
Results: A total of 53 paediatric patients (40 UC, 13 CD) from 27 institutions, with a mean age of 15.0 years, were included. The incidence of AEs, ADEs and FPs were 18.9%, 5.7% and 20.8%, respectively. The ADEs included abdominal discomfort in 2 (3.8%) patients and one patient each with fever, nausea/vomiting and headache (1.9% each). The FPs included blood access failure in 10 patients (18.9%), venous pressure elevation in 4 (7.5%), clot formation in the apheresis lines in 2 (3.8%) and venous access difficulty in 1 patient (1.9%). A total of 17 patients (32.1%) discontinued GMA therapy ahead of the planned treatment schedule. Among these patients, the GMA therapy was discontinued for the following reasons: (1) decision by the physician (n = 12), (2) withdrawal due to AE (n = 4) and (3) withdrawal by own wish (n = 1); none were discontinued due to ADE and FP. The effectiveness of the GMA was assessed in 29 UC patients. The remission rate of the paediatric UC patients was 43.5%. Conclusions: There were AEs and FPs in approximately 20% of paediatric patients with IBD treated by GMA, but none of these discontinued the GMA treatment due to ADE or FP. Remission was achieved by GMA in 44% of the paediatric UC patients. This study showed that GMA was well tolerated treatment option for the paediatric IBD patients.
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
Dan Turner 1, Frank M Ruemmele 2, Esther Orlanski-Meyer 1, Anne M Griffiths 3, Javier Martin de Carpi et al. J Pediatr Gastroenterol Nutr. 2018 Aug;67(2):257-291. doi: 10.1097/MPG.0000000000002035.
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.
Changes in Treatment with Granulocyte and Monocyte Adsorptive Apheresis from the Past to Future in Patients with Inflammatory Bowel Disease
Shingo Kato, Akira Ishibashi, Kaori Sugiura, Kazuhito Kani, Tomonari Ogawa, Hajime Hasegawa, Koji Yakabi, Contrib Nephrol 2018;196:200-208.
GMA decreases inflammatory cytokines and upregulates regulatory T cells. Intensive GMA is significantly more effective than weekly GMA in patients with IBD. The frequency of GMA sessions per week positively correlates with treatment effects. GMA can be safely used in pregnant women and children because of its low adverse event rates. Maintenance therapy and rescue therapy for loss of response of anti-tumor necrosis factor (TNF)-α antibodies are effective. Optimal patients who responded to combination therapy with infliximab and GMA showed aggravation characteristics against infliximab treatment at week 4. Key Message: Prospective randomized blinded studies using a sham column should be performed for the loss of response against anti-TNF-α antibodies.
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.
Treatment options for children and adolescents with Inflammatory Bowel Disease: Is granulomonocytapheresis an effective alternative to drug therapy?
Tomotaka Tanaka 1, Takayuki Yamamoto 2, Koji Sawada 3, Rodolfo Sacco 4 , Expert Rev Gastroenterol Hepatol. 2017 Aug;11(8):749-758.
Patients with inflammatory bowel diseases (IBD) require life-long medications, which even if effective have the potential to cause adverse effects as additional morbidity factors. In pediatric patients, drug therapy has more serious limitations, including impaired physical and mental development. A non-drug therapeutic option is believed to be depletion of elevated and activated granulocytes and monocytes known to release inflammatory cytokines, like the CD14+CD16+ monocyte phenotype known to release tumor necrosis factor-α. Areas covered: Granulomonocyteapheresis (GMA) with an Adacolumn as a treatment option for IBD patients has been applied for the past 15 years. This article reviews the argument that GMA is a relevant and effective non-pharmacologic intervention in pediatric IBD setting. Expert commentary: GMA with an Adacolumn has shown promise in adult, pediatric, and adolescent patients with active IBD. There is evidence of post-GMA immunomodulation in terms of increased regulatory T-cell and B-cell activities. Additionally, patients who respond to GMA may attain a favorable long-term clinical course by avoiding pharmacologicals during an early phase of their active IBD. GMA has a good safety profile, especially in difficult-to-treat and pediatric settings. An additional trial is warranted to assess the efficacy of GMA in the early phase of pediatric IBD to optimize patient selection.
Granulocyte and monocyte apheresis can control juvenile generalised pustular psoriasis with mutation of the IL36RN gene.
Y Koike 1, M Okubo 1, T Kiyohara 1, R Fukuchi 1, Y Sato 1, S Kuwatsuka 1, T Takeichi 2, M Akiyama 2, K Sugiura 3, A Utani 1 , Br J Dermatol. 2017 Dec;177(6):1732-1736.
Granulocyte monocyte apheresis, a process associated with few adverse events, promptly controlled the GPP of our paediatric patient, and has potential as a suitable alternative treatment for paediatric patients with DITRA.
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.
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