Kazuki Kakimoto ¹, Minoru Matsuura ², Takumi Fukuchi ³, Hitoshi Hongo ⁴, Tsuguhiro Kimura ⁴, Nobuo Aoyama ⁵, Yorihide Okuda ⁶, Kazuki Aomatsu ⁷, Noriko Kamata ⁸, Yoko Yokoyama ⁹, Chiemi Mizuno ¹⁰, Takuya Inoue ¹, Takako Miyazaki ¹, Shiro Nakamura ¹, Kazuhide Higuchi ¹, Hiroshi Nakase ¹¹ , Crohns Colitis 360. 2020 Sep 23;2(4):otaa073.

GMA shows effectiveness in inducing remission in UC patients not receiving steroid.

https://pubmed.ncbi.nlm.nih.gov/34192247/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7797742/pdf/otaa073.pdf

Daniel Vasile Balaban, Mariana Jinga, Crohn’s Disease Recent Advances

While leukocyte-derived proinflammatory cytokines have been validated as successful targets in IBD treatment, so should leukocytes themselves be considered as treatment options. As activated leukocytes migrate into the bowel wall and drive the inflammatory cascade in IBD patients, their depletion by apheresis techniques are considered beneficial to control the mucosal inflammation.

Leukapheresis, consisting in either granulomonocyte apheresis or leukocyte apheresis, are cell-based therapies with promising results in some patient categories and with a good safety profile. They have been studied as an alternative in patients with steroid toxicity, dependency or refractoriness, or in the event of contraindications to conventional therapy. Most of the early studies were not controlled, with only a few randomized controlled trials providing quality data on their efficacy. Future studies should be designed to look at selection of IBD patients who benefit most and safely from this non-pharmacological therapy.

https://www.intechopen.com/chapters/73330

Anand Padmanabhan ¹, Laura Connelly-Smith ², Nicole Aqui ³, Rasheed A Balogun ⁴, Reinhard Klingel ⁵, Erin Meyer ⁶, Huy P Pham ⁷, Jennifer Schneiderman ⁸, Volker Witt ⁹, Yanyun Wu ¹⁰, Nicole D Zantek ¹¹, Nancy M Dunbar ¹², Guest Editor Joseph Schwartz ¹³ ,J Clin Apher. 2019 Jun;34(3):171-35

The American Society for Apheresis (ASFA) Journal of Clinical Apheresis (JCA) Special Issue Writing Committee is charged with reviewing, updating and categorizing indications for the evidence-based use of therapeutic apheresis (TA) in human disease. Since the 2007 JCA Special Issue (Fourth Edition), the committee has incorporated systematic review and evidence-based approaches in the grading and categorization of apheresis indications. This Eighth Edition of the JCA Special Issue continues to maintain this methodology and rigor in order to make recommendations on the use of apheresis in a wide variety of diseases/conditions. The JCA Eighth Edition, like its predecessor, continues to apply the category and grading system definitions in fact sheets. The general layout and concept of a fact sheet that was introduced in the Fourth Edition, has largely been maintained in this edition. Each fact sheet succinctly summarizes the evidence for the use of TA in a specific disease entity or medical condition. The Eighth Edition comprises 84 fact sheets for relevant diseases and medical conditions, with 157 graded and categorized indications and/or TA modalities. The Eighth Edition of the JCA Special Issue seeks to continue to serve as a key resource that guides the utilization of TA in the treatment of human disease.

https://pubmed.ncbi.nlm.nih.gov/31180581/

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.

https://academic.oup.com/ecco-jcc/article/13/Supplement_1/S281/5301146?login=true

N Ueno, Y Murakami, T Iwama, T Sasaki, T Kunogi, K Takahashi, K Tanaka, K Ando, S Kashima, Y Inaba, K Moriichi, H Tanabe, M Taruishi, M Fujiya, T Okumura, Journal of Crohn’s and Colitis, Volume 13, Issue Supplement_1, March 2019

Fcal is considered to be a useful and objective predictor of the efficacy of GMA treatment in UC patients and superior to symptomatic scores and blood parameters

https://academic.oup.com/ecco-jcc/article/13/Supplement_1/S423/5300757

Mariko Sawada

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.

http://www.atalacia.com/isfa/data/abstract.pdf

Kengo Furuichi, Takashi Wada Contrib Nephrol  2018;196:188-193. doi: 10.1159/000485721. Epub 2018 Jul 24

Plasma exchange or double filtration plasmapheresis for rapidly progressive glomerulonephritis, and low-density lipoprotein (LDL) apheresis or leukocytapheresis for nephritic syndrome are two major apheresis therapies for kidney diseases. In addition to these apheresis therapies, plasma exchange for lupus nephritis or LDL apheresis for refractory focal segmental glomerulonephritis is clinically valuable and established. Although several possibilities of apheresis for kidney diseases were speculated in animal experiments or human studies, clinical applications have thus far been limited. In addition to clinical benefits of apheresis, reports revealed suggestive mechanisms of apheresis for the diseases. Moreover, these therapies would have a great potential for kidney diseases. Further studies are needed to establish the effectiveness of apheresis in kidney diseases in more depth.

Apheresis for Kidney Disease – PubMed (nih.gov)

Rolf Bambauer ¹, Reinhard Latza ², Daniel Burgard ³, Ralf Schiel ⁴ ,

Ther Apher Dial 2017 Feb;21(1):6-21.

Here, the authors provide an overview of the most important pathogenic aspects indicating that TA can be a supportive therapy in systemic autoimmune diseases such as renal and neurological disorders. For the immunological diseases that can be treated with TA, the guidelines of the German Working Group of Clinical Nephrology and of the Apheresis Committee of the American Society for Apheresis are cited.

https://pubmed.ncbi.nlm.nih.gov/28078733/

Masanao Sakanoue ¹, Yuko Higashi ¹, Takuro Kanekura ¹ ,Ther Apher Dial. 2017 Dec;21(6):628-634.

The clinical effectiveness of GMA may be attributable to the inhibition of pro-inflammatory cytokines and the induction of anti-inflammatory MDSCs by iC3b activation via the CA beads in the GMA column.

https://pubmed.ncbi.nlm.nih.gov/28941055/

Zhenfei Liu ¹, Xueliang Jiang ², Chengcheng Sun ³ ,Eur J Intern Med. 2016 Dec;36:e26-e27.

https://pubmed.ncbi.nlm.nih.gov/27614377/