Ikeda, Hitoshi; Ishimaru, Yuki; Takayasu, Hajime; Fujino, Junko; Kisaki, Yoshiyuki; Otani, Yushi; Yamagishi, Junko; Tahara, Kazunori. J Pediatr Gastroenterol Nutr 2006; 43:592-6. doi: 10.1097/01.mpg.0000237928.07729.79

Objectives: Granulocyte apheresis (GCAP), involving the removal of granulocytes from the blood, may improve clinical symptoms and facilitate a reduction in the dose of steroids in adult patients with ulcerative colitis. As a preliminary trial, GCAP was used to taper the dose of steroids in 4 pediatric patients with ulcerative colitis. Methods: Three males and 1 female ranging from 11 to 17 years old were treated with GCAP once per week for 5 consecutive weeks/course. The ages of patients at clinical onset ranged from 8 to 12 years and the length of time from the clinical onset to GCAP treatment ranged from 28 to 58 months (median, 38.5 months). Results: In 2 patients, symptoms and signs indicating disease activity improved after 2 courses of GCAP. Laboratory data and endoscopic findings also improved after treatment and the clinical efficacy was judged to be excellent in these patients. In 1 patient, GCAP improved laboratory and endoscopic hallmarks, but bloody stools persisted. Finally, the treatment was ineffective in the fourth patient who eventually underwent surgery. Conclusions: GCAP is effective in improving clinical symptoms and may play an important role in converting steroid therapy to other treatments in children with steroid-refractory or steroid-dependent ulcerative colitis.

https://journals.lww.com/jpgn/FullText/2006/11000/Efficacy_of_Granulocyte_Apheresis_in_Pediatric.8.aspx

Takayuki Yamamoto, Satoru Umegae, Koichi Matsumoto February 2006 World Journal of Gastroenterology 12(4):520-5 DOI:10.3748/wjg.v12.i4.520

Active ulcerative colitis (UC) is frequently associated with infiltration of a large number of leukocytes into the bowel mucosa. Therefore, removal of activated circulating leukocytes by apheresis has the potential for improving UC. In Japan, since April 2000, leukocytapheresis using Adacolumn has been approved as the treatment for active UC by the Ministry of Health and Welfare. The Adacolumn is an extracorporeal leukocyte apheresis device filled with cellulose acetate beads, and selectively adsorbs granulocytes and monocytes / macrophages. To assess the safety and clinical efficacy of granulocyte and monocyte adsorptive apheresis (GMCAP) for UC, we reviewed 10 open trials of the use of GMCAP to treat UC. One apheresis session (session time, 60 min) per week for five consecutive weeks (a total of five apheresis sessions) has been a standard protocol. Several studies used modified protocols with two sessions per week, with 90-min session, or with a total of 10 apheresis sessions. Typical adverse reactions were dizziness, nausea, headache, flushing, and fever. No serious adverse effects were reported during and after GMCAP therapy, and almost all the patients could complete the treatment course. GMCAP is safe and well-tolerated. In the majority of patients, GMCAP therapy achieved clinical remission or improvement. GMCAP is a useful alternative therapy for patients with steroid-refractory or -dependent UC. GMCAP should have the potential to allow tapering the dose of steroids, and is useful for shortening the time to remission and avoiding re-administration of steroids at the time of relapse. Furthermore, GMCAP may have efficacy as the first-line therapy for steroid-naive patients or patients who have the first attack of UC. However, most of the previous studies were uncontrolled trials. To assess a definite efficacy of GMCAP, randomized, double blind, sham-controlled trials are necessary. A serious problem with GMCAP is cost; a single session costs ¥145 000 ($1 300). However, if this treatment prevents hospital admission, re-administration of steroids and surgery, and improves a quality of life of the patients, GMCAP may prove to be cost-effective.

https://www.researchgate.net/publication/7286897_Safety_and_clinical_efficacy_of_granulocyte_and_monocyte_adsorptive_apheresis_therapy_for_ulcerative_colitis

[Article in Korean ]Hyo Jong Kim ¹, Joo Sung Kim, Dong Soo Han, Suk-Kyun Yang, Ki Baik Hahm, Woo In Lee, Seog-Woon Kwon, Jai Hyun Choi, Won Ho Kim, Kyu Yong Choi, In Sung Song Korean J Gastroenterol  2005 Jan;45(1):34-44. PMID: 15665566

Background/aims: In chronic inflammatory conditions such as ulcerative colitis (UC), the migration of granulocytes and monocytes/macrophages from the circulation into the colonic mucosa is especially important in maintaining inflammation. The aim of this trial was to assess safety and efficacy of granulocyte and monocyte adsorption apheresis in patients with moderate-to-severe UC refractory to conventional drug therapies. Methods: Twenty-seven patients with moderate (55.6%) to severe (44.4%) active UC refractory to conventional drug therapies who had no changes in their conventional therapy regimen in the past two weeks before the recruitment were enrolled in an open-label trial. Concomitant medications were allowed, and steroids were tapered down according to the clinical activity during the course. We used an adsorptive type extracorporeal column (Adacolumn; JIMRO, Takasaki, Japan), which selectively adsorb granulocytes and monocytes. Patients took five apheresis sessions, each with 60 minutes duration for 5 consecutive weeks. The primary efficacy variables were clinical disease activity, short inflammatory bowel disease questionnaire (SIBDQ), C-reactive protein (CRP), and endoscopic scores. These variables were scored at regular intervals, and analyzed at week 7 on an intention-to-treat (ITT) principles. Results: At 7 weeks, 70.4% of patients showed overall improvement. Clinical disease activity (p < 0.0001), endoscopic score (p < 0.001), and the quality of life as assessed by SIBDQ (p < 0.0001) were significantly improved after the therapy. In 56.3% of concomitant steroid users, tapering down or discontinuation of steroids was possible. Treatment was well tolerated, and no severe adverse events were observed. Conclusions: Adacolumn was very efficacious in patients with moderate-to-severe active UC refractory to conventional drug therapy, but further assessment is needed.

https://pubmed.ncbi.nlm.nih.gov/15665566/

Cuenca, F & Paredes, J & Mendoza, J & Cruz, D & Herrero, A & Díaz-Rubio, M.Revista española de enfermedades digestivas : organo oficial de la Sociedad Española de Patología Digestiva .2004,96. 501-3, 504. DOI:10.4321/S1130-01082004000700007.

Objective: To describe our experience with granulocyte apheresis to induce remission in patients with active Crohn’s disease refractory to conventional treatment. We summarize the results previously obtained with this technique.

Conclusions: Granulocyte apheresis is a safe and well tolerated therapeutic modality that can be a valid therapeutic alternative in the induction of remission in inflammatory bowel disease, although controlled clinical trials must be conducted to define long-term efficacy, as well as to establish “optimal patient” selection, re-treatment interval, and number of sessions.

https://pubmed.ncbi.nlm.nih.gov/15283632/

Masakazu Takazoe ¹, Torao Tanaka, Kenji Kondo, Toshiki Ichimori, Toshio Shinoda Ther Apher 2002 Aug;6(4):305-11. doi: 10.1046/j.1526-0968.2002.00445.x.

The immunological and genetic pathogeneses of inflammatory bowel disease (IBD) have been well elucidated in the recent years. The pharmacologic treatment of IBDs accordingly becomes to focus upon the individual pathologic step (targeting therapy), whereas the therapeutic action is not yet a pinpoint one. It has been known recently that new drugs such as biological immunomodulating agents and anti-inflammatory cytokines have better short-term effects in some respects than the conventional drugs, and they might alter the treatment strategy of IBDs in the near future. The limitation of pharmacologic treatments mainly results from adverse effects of the drugs, i.e. infection susceptibility, oncogenesis, teratogenesis and so forth. The extracorporeal therapy such as leukocytapheresis and photopheresis is reportedly effective for IBDs probably through immunomodulation such as decrease in circulating activated T-lymphocytes and activated granulocytes that play a central role in the pathogenesis of IBD. It can be said that these extracorporeal treatment methods have advantage of rapid action and lack of serious adverse effects to drug therapy.

https://pubmed.ncbi.nlm.nih.gov/12164801/