Journal of Gastroenterology

, Volume 47, Issue 1, pp 49–55

Processed blood volume impacts clinical efficacy in patients with ulcerative colitis undergoing adsorptive depletion of myeloid lineage leucocytes

  • Naoki Yoshimura
  • Tokuma Tadami
  • Takaaki Kawaguchi
  • Minako Sako
  • Hiroshi Yoshimoto
  • Toshihiko Yamaka
  • Masakazu Takazoe
Original Article—Alimentary Tract



Hitherto, therapeutic depletion of granulocytes and monocytes by adsorption (GMA) has been associated with significant and insignificant efficacy in patients with ulcerative colitis (UC). Further, the processed blood volume in one GMA session has been fixed at 30 mL/min × 60 min, regardless of patients’ body weight (BW). We were interested to see the efficacy and safety of GMA when administered in relation to patients’ BW.


Sixty patients were randomly assigned to the routine GMA (n = 30) and to GMA adjusted to patients’ BW, 60 mL/kg (n = 30). GMA was done with the Adacolumn, up to 10 sessions over 10 weeks. At entry and 1 week post last GMA, patients were clinically and endoscopically evaluated. Remission was defined as clinical activity index (CAI) ≤4, whereas mucosal remission was defined as endoscopic index (EI) ≤3.


In the BW group, the processed volume/session was 3,260 ± 581 versus 1,800 mL in the routine group (P < 0.001). In the BW group, 25 of 30 patients (83.3%) achieved remission versus 19 of 30 patients (63.3%) in the routine group. The average CAI in the BW group fell from 9.6 ± 2.6 to 2.3 ± 2.1 versus from 9.1 ± 2.4 to 4.0 ± 2.1 (P < 0.05) in the routine group. Similarly, the EI in the BW group fell from 9.4 ± 1.3 to 2.1 ± 2.1 versus from 9.2 ± 1.8 to 4.5 ± 2.3 (P < 0.01).


GMA adjusted to patients’ BW and at a vastly greater processed volume produces significantly higher efficacy as compared with the routine GMA protocol. Further, in this study, up to twofold higher processed volume caused no safety concern.


Ulcerative colitis Myeloid lineage leucocytes Processed blood volume Granulocytes and monocytes adsorptive apheresis Body weight 


  1. 1.
    Hanauer SB. Inflammatory bowel disease: epidemiology, pathogenesis, and therapeutic opportunities. Inflamm Bowel Dis. 2006;12:S3–9.PubMedCrossRefGoogle Scholar
  2. 2.
    Allison MC, Dhillon AP, Lewis WG, Pounder RE, editors. Inflammatory bowel disease. London: Mosby; 1998. p. 9–95.Google Scholar
  3. 3.
    Present DH. How to do without steroids in inflammatory bowel disease. Inflamm Bowel Dis. 2000;6:48–57.PubMedCrossRefGoogle Scholar
  4. 4.
    van Dullemen HM, van Deventer SJ, Hommes DW. Treatment of Crohn’s disease with anti-tumour necrosis factor chimeric monoclonal antibody (cA2). Gastroenterology. 1995;109:129–35.PubMedCrossRefGoogle Scholar
  5. 5.
    Rutgeerts P, Sandborn WJ, Feagan BG, Reinisch W, Olson A, Johanns J, et al. Infliximab for induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2005;353:2462–76.PubMedCrossRefGoogle Scholar
  6. 6.
    McCarthy DA, Rampton DS, Liu Y-C. Peripheral blood neutrophils in inflammatory bowel disease: morphological evidence of in vivo activation in active disease. Clin Exp Immunol. 1991;86:489–93.PubMedCrossRefGoogle Scholar
  7. 7.
    Tibble JA, Sigthorsson G, Bjarnason I. Surrogate markers of intestinal inflammation are predictive of relapse in patients with inflammatory bowel disease. Gastroenterology. 2000;119:15–22.PubMedCrossRefGoogle Scholar
  8. 8.
    Passlick B, Flieger D, Ziegler-Heitbrock HW. Identification and characterization of a novel monocyte subpopulation in human peripheral blood. Blood. 1989;74:2527–34.PubMedGoogle Scholar
  9. 9.
    Belge KU, Dayyani F, Horelt A. The proinflammatory CD14+CD16+DR++ monocytes are a major source of TNF. J Immunol. 2002;168:3536–42.PubMedGoogle Scholar
  10. 10.
    Hanai H, Iida T, Takeuchi K, Watanabe F, Yamada M, Kikuyama M, et al. Adsorptive depletion of elevated proinflammatory CD14+CD16+DR++ monocytes in patients with inflammatory bowel disease. Am J Gastroenterol. 2008;103:1210–6.PubMedCrossRefGoogle Scholar
  11. 11.
    Cohen RD. Treating ulcerative colitis without medications—“Look Mom, no drugs!” Gastroenterology. 2005;128:235–6.PubMedCrossRefGoogle Scholar
  12. 12.
    Sands BE, Sandborn WJ, Feagan B, Löfberg R, Hibi T, Vandervoort MK, et al. A randomized, double-blind, sham-controlled study of granulocyte/monocyte apheresis for active ulcerative colitis. Gastroenterology. 2008;135:400–9.PubMedCrossRefGoogle Scholar
  13. 13.
    Saniabadi AR, Hanai H, Takeuchi K, Umemura K, Nakashima M, Adachi T, et al. Adacolumn, an adsorptive carrier based granulocyte and monocyte apheresis device for the treatment of inflammatory and refractory diseases associated with leukocytes. Ther Apher Dial. 2003;7:48–59.PubMedCrossRefGoogle Scholar
  14. 14.
    Shimoyama T, Sawada K, Hiwatashi N, Sawada T, Matsueda K, Munakata A, et al. Safety and efficacy of granulocyte and monocyte adsorption apheresis in patients with active ulcerative colitis: a multicenter study. J Clin Apher. 2001;16:1–9.PubMedCrossRefGoogle Scholar
  15. 15.
    Hanai H, Watanabe F, Takeuchi K, Iida T, Yamada M, Iwaoka Y, et al. Leukocyte adsorptive apheresis for the treatment of active ulcerative colitis: a prospective, uncontrolled study. Clin Gastroenterol Hepatol. 2003;1:28–35.PubMedCrossRefGoogle Scholar
  16. 16.
    Suzuki Y, Yoshimura N, Saniabadi AR, Saito Y. Selective granulocytes and monocyte adsorptive apheresis as a first-line treatment for steroid naïve patients with active ulcerative colitis: a prospective uncontrolled study. Dig Dis Sci. 2004;49:565–71.PubMedCrossRefGoogle Scholar
  17. 17.
    Saniabadi AR, Hanai H, Suzuki Y, Ohmori T, Sawada K, Yoshimura N, et al. Adacolumn for selective leukocytapheresis as a non-pharmacological treatment for patients with disorders of the immune system: an adjunct or an alternative to drug therapy? J Clin Apher. 2005;20:171–84.Google Scholar
  18. 18.
    Muratov V, Lundahl J, Ulfgren AK, Elvin K, Fehrman I, Ahlborg N, et al. Down-regulation of interferon-gamma parallels clinical response to selective leukocyte apheresis in patients with inflammatory bowel disease: a 12-month follow-up study. Int J Colorectal Dis. 2006;21:493–504.PubMedCrossRefGoogle Scholar
  19. 19.
    Maiden L, Takeuchi K, Baur R, Bjarnason I, O’Donohue J, Forgacs I, et al. Selective white cell apheresis reduces relapse rates in patients with IBD at significant risk of clinical relapse. Inflamm Bowel Dis. 2008;14:1413–8.PubMedCrossRefGoogle Scholar
  20. 20.
    Naganuma M, Funakoshi S, Sakuraba A, Takagi H, Inoue N, Ogata H, et al. Granulocytapheresis is useful as an alternative therapy in patients with steroid-refractory or -dependent ulcerative colitis. Inflamm Bowel Dis. 2004;10:251–7.PubMedCrossRefGoogle Scholar
  21. 21.
    Yamamoto T, Umegae S, Kitagawa T. Granulocyte and monocyte adsorptive apheresis in the treatment of active distal ulcerative colitis: a prospective, pilot study. Aliment Pharmacol Ther. 2004;20:783–92.PubMedCrossRefGoogle Scholar
  22. 22.
    Domènech E, Hinojosa J, Esteve-Comas M, Gomollón F, Herrera JM, Bastida G, et al. Granulocyteaphaeresis in steroid-dependent inflammatory bowel disease: a prospective, open, pilot study. Aliment Pharmacol Ther. 2004;20:1347–52.PubMedCrossRefGoogle Scholar
  23. 23.
    Suzuki Y, Yoshimura N, Fukuda K, Shirai K, Saito Y, Saniabadi AR. A retrospective search for predictors of clinical response to selective granulocyte and monocyte apheresis in patients with ulcerative colitis. Dig Dis Sci. 2006;51:2031–8.PubMedCrossRefGoogle Scholar
  24. 24.
    Tanaka T, Okanobu H, Yoshimi S, Murakami E, Kogame A, Imagawa H, et al. In patients with ulcerative colitis, adsorptive depletion of granulocytes and monocytes impacts mucosal level of neutrophils and clinically is most effective in steroid naïve patients. Dig Liver Dis. 2008;40:731–6.PubMedCrossRefGoogle Scholar
  25. 25.
    Hanai H, Watanabe F, Yamada M, Sato Y, Takeuchi K, Iida T, et al. Adsorptive granulocyte and monocyte apheresis versus prednisolone in patients with corticosteroid-dependent moderately severe ulcerative colitis. Digestion. 2004;70:36–44.PubMedCrossRefGoogle Scholar
  26. 26.
    Hibi T, Sameshima Y, Sekiguchi Y, Hisatome Y, Maruyama F, Moriwaki K, et al. Treating ulcerative colitis by Adacolumn therapeutic leucocytapheresis: clinical efficacy and safety based on surveillance of 656 patients in 53 centres in Japan. Dig Liver Dis. 2009;41:570–7.PubMedCrossRefGoogle Scholar
  27. 27.
    Rachmilewitz D, on behalf of an international study group. Coated mesalazine (5-aminosalicylic acid) versus sulphasalazine in the treatment of active ulcerative colitis: a randomized trial. Br Med J. 1989;298:82–6.CrossRefGoogle Scholar
  28. 28.
    Saniabadi AR, Hanai H, Fukunaga K, Sawada K, Shima C, Bjarnason I, et al. Therapeutic leucocytapheresis for inflammatory bowel disease. Transf Apher Sci. 2007;37:191–200.CrossRefGoogle Scholar
  29. 29.
    Hanauer SB. Medical therapy of ulcerative colitis. Gastroenterology. 2004;126:1582–92.PubMedCrossRefGoogle Scholar
  30. 30.
    D’Haens G, Lemmens L, Geboes K. Intravenous cyclosporine versus intravenous corticosteroids as single therapy for severe attacks of ulcerative colitis. Gastroenterology. 2001;120:1323–9.PubMedCrossRefGoogle Scholar
  31. 31.
    Hanauer SB. Can cyclosporine go it alone in severe ulcerative colitis. Curr Gastroenterol Rep. 2001;3:455–6.PubMedCrossRefGoogle Scholar
  32. 32.
    Taffet SL, Das KM. Sulfasalazine-adverse effects and desensitization. Dig Dis Sci. 1983;28:833–42.PubMedCrossRefGoogle Scholar
  33. 33.
    Tanaka T, Okanobu H, Kuga Y, Yoshifuku Y, Fujino H, Miwata T, et al. Clinical and endoscopic features of responders and non-responders to adsorptive leucocytapheresis: a report based on 120 patients with active ulcerative colitis. Gastroenterol Clin Biol. 2010;34:687–95.PubMedCrossRefGoogle Scholar
  34. 34.
    Saniabadi AR, Hanai H. Therapeutic apheresis from the early civilizations to the twenty-first century. Gastroenterol Clin Biol. 2010;34:645–8.PubMedCrossRefGoogle Scholar
  35. 35.
    Sakuraba A, Motoya S, Watanabe K, Nishishita M, Kanke K, Suzuki Y, et al. An open-label prospective randomized multicenter study shows very rapid remission of ulcerative colitis by intensive granulocyte and monocyte adsorptive apheresis as compared with routine weekly treatment. Am J Gastroenterol. 2009;104:2990–5.PubMedCrossRefGoogle Scholar
  36. 36.
    Hanai H, Takeda Y, Eberhardson M, Gruber R, Saniabadi AR, Winqvist O, et al. The mode of actions of the Adacolumn therapeutic leucocytapheresis in patients with inflammatory bowel disease: a concise review. Clin Exp Immunol. 2011;163:50–8.PubMedCrossRefGoogle Scholar
  37. 37.
    Kanke K, Nakano M, Hiraishi H, Terano A. Evaluation of granulocyte/monocyte apheresis therapy for active ulcerative colitis. Dig Liv Dis. 2004;36:512–8.CrossRefGoogle Scholar

Copyright information

© Springer 2011

Authors and Affiliations

  • Naoki Yoshimura
    • 1
  • Tokuma Tadami
    • 1
  • Takaaki Kawaguchi
    • 1
  • Minako Sako
    • 1
  • Hiroshi Yoshimoto
    • 1
  • Toshihiko Yamaka
    • 1
  • Masakazu Takazoe
    • 1
  1. 1.Department of Internal MedicineSocial Insurance Central General HospitalTokyoJapan

Personalised recommendations