Leukocytapheresis

Accumulating evidence suggests that an abnormal T-cell-specific immune response to host flora may be a driving force in abnormal inflammation in UC. There is also reasonable consensus that the intestinal epithelium in patients with UC is dominated by leukocytes, macrophages and CD4+ lymphocytes with a T-helper 2 phenotype. Recruitment of these inflammatory cells from the systemic circulation into the intestinal epithelium may be a critical step in the amplification of the inflammatory response. Each cell can generate pro-inflammatory mediators such as cytokines, chemokines, growth factors and nitric oxide radicals which will deteriorate inflamed epithelium. Leukocytapheresis (LCAP) is a therapy based on a selective removal of leukocytes from systemic circulation, obtained by the passage of blood either through a column or through a filter. So far, this form of therapy has mainly been studied in Japan. Recent studies demonstrated that LCAP might be useful for active Crohn's disease and UC after failure of conventional drug treatments.

In an early study, the effect of LCAP on maintaining remission was evaluated in steroid-refractory UC after induction of remission with the same therapeutic procedure. Via induction-LCAP, six patients reached complete remission and one reached partial remission and was then treated with maintenance-LCAP. Four of them were maintained in remission without steroid treatment over 12 months. Recurrence was observed in three patients 3-6 months after the beginning of maintenance, and two of them re-entered remission by re-induction. One patient then presented a second recurrence and underwent a total colectomy [75].

Sakata et al. evaluated 51 UC patients with severe or moderate disease, who failed to respond to conventional therapy. Thirty-three patients went into complete remission after the first induction therapy with significant improvement of the activity score. Ten of them relapsed, but 21 maintained remission with LCAP maintenance [76].

In another study [77], 60 UC patients on sul-fasalazine for at least 8 weeks prior to the treatment received a total of 10 sessions of LCAP therapy (once or twice a week). Most patients were also on pred-nisolone at entry, and had steroids tapered or discontinued during the study depending on the level of improvement. Fifty patients responded to therapy, 14 by achieving a complete remission, with no serious adverse effects.

The endoscopic severity scores were markedly improved in 22 of 46 patients and 68% of steroid-dependent cases could stop steroids. The average dose of steroid after 10 sessions decreased from 15.3 to 3.6 mg/day. In terms of symptom activity, LCAP is more effective in patients who during the course of their disease had received a low cumulative dosage of steroids. There was a highly significant association between symptomatic improvement of diarrhoea, abdominal pain and rectal bleeding and duration of apheresis or number of sessions per week. Five of the non-responders to LCAP improved with conventional therapy, the other five underwent elective colecto-my. No additional maintenance therapy was provided. The improvement continued for a mean duration of 199 days (range: 21-614). The time to relapse was negatively correlated with endoscopic and histologic findings and the cumulative dosage of steroids. Further studies will clarify whether this approach will also prove cost-effective in Western populations.

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