2 The procedure

2.1 Indications

2.1.1 Ulcerative colitis and Crohn's disease are the most common forms of inflammatory bowel disease. Ulcerative colitis causes inflammation and ulceration of the rectum and colon. Symptoms include bloody diarrhoea and rectal bleeding. Crohn's disease usually causes inflammation and ulceration of the small intestine, but it can affect any part of the digestive tract. The main symptoms are abdominal pain, diarrhoea and weight loss. Both ulcerative colitis and Crohn's disease are chronic conditions characterised by periods of clinical relapse and remission.

2.1.2 Conservative treatments include dietary measures and medication to control inflammation, which may include immunosuppressants. Patients with ulcerative colitis that does not respond to medical therapy may be treated with surgery to remove the colon. Although surgery may also be used for patients with Crohn's disease, it may not be curative and the disease often recurs in a different part of the digestive tract.

2.2 Outline of the procedure

2.2.1 Leukapheresis involves extracorporeal removal of leukocytes from the blood, either by centrifugation or through an adsorptive system. In each system, venous blood is removed in a continuous flow, anticoagulated, processed to deplete the leukocytes and returned to the circulation.

2.2.2 Different apheresis systems remove different populations of white blood cells. Leukapheresis using centrifugation removes a proportion of neutrophils and lymphocytes. Filter columns, which may contain cellulose acetate beads or a polyester fibre filter, remove a large proportion of granulocytes and monocytes and some also remove lymphocytes. The exact mode of action of these procedures is unknown.

2.3 Efficacy

2.3.1 In one randomised controlled trial of patients with ulcerative colitis, 74% (29/39) of patients treated with leukapheresis had an 'excellent' or 'moderate' improvement in symptoms, compared with 38% (14/37) of patients treated with high-dose steroids (p = 0.005).

2.3.2 In four case series, 54% (24/44) to 82% (32/39) of patients with ulcerative colitis had an initial remission of disease after treatment. In one study, the proportion of patients in clinical remission dropped from 82% (32/39) at 12 weeks to 67% (26/39) at 12 months after the final treatment. In two further studies, 30% (10/33) and 39% (13/33) of patients relapsed during maintenance therapy after initial complete remission.

2.3.3 In a small randomised controlled trial of patients with Crohn's disease, 100% (12/12) of patients treated with leukapheresis were successfully withdrawn from steroid therapy, compared with 67% (10/15) of patients who were not treated with leukapheresis (p = 0.074). There was no significant difference between the two groups in disease recurrence at 18-month follow-up. For more details, refer to the Sources of evidence.

2.3.4 The Specialist Advisors stated that some uncertainty remained about the efficacy of leukapheresis for inflammatory bowel disease because data from randomised controlled trials were insufficient.

2.4 Safety

2.4.1 Most studies reported only mild adverse events such as dizziness, light headedness, headache and flushing. In three case series, the proportion of patients experiencing at least one non-severe adverse event ranged from 9% (5/53) to 18% (7/39).

2.4.2 In a randomised controlled trial, the incidence of adverse events was significantly lower in the group treated with leukapheresis than in the group treated with high-dose steroids (24% versus 47%, p < 0.001). In the same trial, adverse events were described as moderate or severe in 12% (5/42) of patients treated with leukapheresis: one patient had toxic shock, one patient had chest pain, one patient had anaemia and two patients had a headache. For more details, refer to the Sources of evidence.

2.4.3 The Specialist Advisors stated that potential adverse events included infection, headache, palpitations, nausea, vomiting, fever, chills, respiratory distress and chest discomfort.

2.5 Other comments

2.5.1 It was noted that leukapheresis is an established technique for other conditions.

2.5.2 It was also noted that there are different techniques for leukapheresis, and these may have different risk and benefit profiles.

Andrew Dillon
Chief Executive
June 2005