Leukocytapheresis Therapy Research Articles

Treatment of inflammatory bowel disease by leukocytapheresis

Studies about leukocytapheresis have emerged with the need of search for alternatives to conventional treatment in inflammatory bowel diseases (IBD). Leukocytapheresis is a novel non-pharmacologic approach for active ulcerative colitis (UC) and Crohn’s disease (CD), in which leukocytes are mechanically removed from the circulatory system. Patients with active IBD treated with leukocytapheresis using a Cellsorba E column between 2012 and 2015, were enrolled in Turkey. In our experience, the results of leukocytapheresis therapy in 6 patients with CD and 20 patients with active UC were overviewed. Leukocytapheresis (10 sessions for remission induction therapy, 6 sessions for maintenance therapy) was applied to the patients with their concomitant medications. Intensive leukocytapheresis (≥4 leukocytapheresis sessions within the first 2 weeks) was used in 30% patients with active severe UC. The overall clinical remission rate in patients with UC was 80%, and the mucosal healing rate was 65%. Patients were followed for an average of 24 months. It was observed that clinical remission has continued in 65% of patients with UC. Mild relapse was observed in 3 patients with UC during follow up period. In 5 patients with CD significant clinical remission was achieved except only one patient. Surgical needs were disappeared in 3 patients with obstructive type Crohn’s disease. Adverse events were seen in only 4.3% of 416 sessions. Any concomitant medications did not increase the incidence of adverse events. Our results indicate that leukocytapheresis is efficacious in improving remission rates with excellent tolerability and safety in patients with IBD.

Univariate analysis to examine predictors of response to leukocytapheresis in ulcerative colitis patients.

Leukocytapheresis (LCAP) is reportedly effective for the treatment of active ulcerative colitis (UC) and is a therapeutic option for steroid-dependent or steroid-resistant patients with UC. However, a consensus regarding the use of LCAP for UC patients has not yet been established. Therefore, we analyzed patients' records to identify predictors of response to LCAP therapy and subsequent recurrence. Between October 2001 and March 2011, we recruited 41 patients who had been diagnosed as having UC and had received LCAP therapy. Patients diagnosed with moderate to severe UC with left-side or total colitis and received LCAP therapy for the first time were enrolled. We retrospectively performed a univariate analysis using the patients' medical records to identify factors affecting the therapeutic effect of LCAP. Body mass index exceeding 18.5 kg/m(2) was found to influence the therapeutic effect of LCAP. Male sex was correlated with a rapid response to LCAP treatment and the maintenance of remission. UC patients experiencing their first attack or had an elevated C-reactive protein level prior to LCAP therapy exhibited a relatively long remission period. In the "after LCAP therapy" group, a low Rachmilewitz endoscopic score, low erythrocyte sedimentation rate, or high white blood cell count was associated with a long remission period. Our results suggest that LCAP should be performed for the treatment of early-onset UC. LCAP can be expected to induce a long remission period, enabling mucosal healing, although the factors that affected the remission period did not influence the therapeutic effect and responsiveness.

AB0475 Increased Plasma Lactoferrin Levels in Leukocytapheresis Therapy in Patients with Rheumatoid Arthritis

ObjectivesTo clarify the mechanism of leukocytapheresis (LCAP) in patients with rheumatoid arthritis (RA).MethodsProtein profiles of blood samples from 2 patients with RA obtained via LCAP column inlet and outlet lines...

Ultrasound Evaluation of the Effects of Leukocytapheresis on Rheumatoid Arthritis

Leukocytapheresis (LCAP) is effective in treating rheumatoid arthritis (RA). Ultrasound (US) examination of joints is useful for evaluating disease activity and therapeutic effects in RA, but the clinical assessment of LCAP therapy with US has been little reported. We investigated the usefulness of US for evaluating the effects of LCAP in patients with RA. US examination was performed in six patients (total of seven cases) who underwent LCAP. Twenty-eight joints (bilateral shoulders, elbows, wrists, 1st to 5th metacarpophalangeal joints, 1st to 5th proximal interphalangeal joints, and knee joints) were evaluated by a systematic multiplanar grey-scale and power Doppler (PD) examination. Disease activity of RA was evaluated using the 28-joint Disease Activity Score with erythrocyte sedimentation rate (DAS28-ESR). Moderate or good responses to LCAP based on the DAS28-ESR were observed in four of the seven cases although C-reactive protein (CRP) and ESR did not decrease. LCAP significantly reduced the mean total PD score 17.3 ± 11.6 to 13.0 ± 10.5 (P = 0.0469). The total PD score decreased in six of the seven cases, and the number of joints with PD score ≥ 2 decreased in five of the seven cases. The rate of decrease in the number of joints with PD score ≥ 2 correlated strongly with the DAS28-ESR and its components, especially swollen joint counts and evaluator's global assessment, but not with the rate of decrease in CRP and ESR. US imaging of joints may be useful for evaluating the therapeutic effects of LCAP on RA compared to other inflammatory parameters.

Successful leukocytapheresis therapy in a patient with rheumatoid arthritis on maintenance hemodialysis

Successful leukocytapheresis therapy in a patient with rheumatoid arthritis on maintenance hemodialysis

Microarray analyses of peripheral whole blood cells from ulcerative colitis patients: Effects of leukocytapheresis

Complementary DNA microarray technology allows the simultaneous analysis of the expression of hundreds to thousands of genes. We applied this technique to clarify the molecular mechanisms underlying the therapeutic effects of leukocytapheresis (LCAP) therapy in patients with ulcerative colitis (UC). A 776-gene microarray analysis was performed using whole blood cells from six normal subjects and six patients with active UC who had undergone filtration LCAP. Widespread gene upregulation was observed in patients with UC, compared with normal subjects. After LCAP, genes with proinflammatory actions, such as CD97, CD74, human leukocyte antigen-DRβ1 and -DP light chain, were downregulated, while genes responsible for antimicrobial actions, such as neutrophil gelatinase-associated lipocalin, and acute phase reactions, such as haptoglobin α1S and α1-acid glycoprotein, were upregulated. In conclusion, we identified several genes expressed in the whole blood cells of UC patients as well as the transcriptional events following LCAP. Following LCAP, the gene profile shifted toward a pattern indicating disease improvement. These results suggest a basis for the molecular mechanisms leading to the therapeutic effects of LCAP and also indicate new therapeutic targets, providing important prognostic information.

Multicenter prospective study for clinical and endoscopic efficacies of leukocytapheresis therapy in patients with ulcerative colitis

Objective.This study aimed to assess the efficacy and tolerability of leukocytapheresis (LCAP) and to investigate predictive factors for mucosal healing and a sustained clinical response in steroid-free and steroid-refractory patients with ulcerative colitis (UC). Material and methods.Thirty-one steroid-free or steroid-refractory patients with active UC were enrolled. Five or ten consecutive sessions of LCAP were performed in each patient. The efficacy and tolerability was then evaluated at weeks 3 and 6. Endoscopic examination was performed at week 6 to evaluate the mucosal healing, and the sustained cumulative response rate was evaluated at 12 months. Results.At week 6, the mean Mayo clinical activity score had decreased significantly from 8.0 to 4.6 in the steroid-free patients and from 8.3 to 3.9 in the steroid-refractory patients. Rachmilewitz's endoscopic index had also decreased significantly from 9.1 to 6.1 in the steroid-free patients and from 10.0 to 5.7 in the steroid-refractory patients. Forty-seven percent of the steroid-free patients and 33% of the steroid-refractory patients achieved mucosal healing. The peripheral platelet counts had decreased significantly at weeks 3 and 6 in the mucosal healing group, compared with the non-mucosal healing group. The patients with a more than 15% platelet reduction had a significantly higher cumulative response rate, compared with the patients without a platelet reduction (p = 0.015). Conclusions.LCAP is beneficial for the induction of mucosal healing in steroid-free and steroid-refractory patients with UC. The degree of platelet reduction during LCAP might be a predictive marker for mucosal healing and a sustained clinical response.

Leukocytapheresis therapy in rheumatoid arthritis in our hospital

Leukocytapheresis therapy in rheumatoid arthritis in our hospital

Su1484 Significance of Endoscopic Mucosal Healing on the Leukocytapheresis Therapy in the Patients With Ulcerative Colitis

Su1484 Significance of Endoscopic Mucosal Healing on the Leukocytapheresis Therapy in the Patients With Ulcerative Colitis

Steroid-sparing strategies in the management of ulcerative colitis: Efficacy of leukocytapheresis

Active ulcerative colitis (UC) is frequently associated with infiltration of a large number of leukocytes into the bowel mucosa. Leukocytapheresis is a novel nonpharmacologic approach for active UC, in which leukocytes are mechanically removed from the circulatory system. Current data indicate that leukocytapheresis is efficacious in improving response and remission rates with excellent tolerability and safety in patients with UC. Corticosteroid therapy remains a mainstay in the treatment of active UC; however, long-term, high doses of corticosteroids usually produce predictable and potentially serious side effects. If leukocytapheresis can spare patients from exposure to corticosteroids, the risk of steroid-induced adverse events should be minimized. This may be of great benefit to patients because severe side effects of steroids seriously impair health-related quality of life. In this article, we reviewed current evidence on whether leukocytapheresis can avoid or reduce the use of corticosteroids in the management of patients with UC. Several studies have shown that leukocytapheresis was effective for steroid-naïve patients with active UC. Furthermore, both short-term and long-term studies have demonstrated the steroid-sparing effects of leukocytapheresis therapy in patients with UC. Although the evidence level is not striking, the available data suggest that leukocytapheresis can avoid or reduce the use of corticosteroids in the management of UC. Large, well-designed clinical trials are necessary to more accurately evaluate the steroid-sparing effects of leukocytapheresis in the management of UC.

Leukocytapheresis for steroid-dependent ulcerative colitis in clinical practice: results of a nationwide Spanish registry

Several small, prospective, open studies suggest that leukocytapheresis might be efficient in patients with steroid-dependent ulcerative colitis (UC). To evaluate the short- and long-term effectiveness of leukocytapheresis for the management of steroid-dependent UC in clinical practice. A Web-based, nationwide database specifically designed to record the efficacy and safety data of leukocytapheresis therapy in UC was available from September 2007 in Spain. Clinical data were collected at treatment baseline, 1 month after the last apheresis session (initial efficacy), and 6 and 12 months thereafter (long-term efficacy). Remission was defined as a Mayo Clinic index ≤2 together with complete steroid withdrawal and response as a decrease of ≥3 from the baseline score. A total of 142 steroid-dependent UC patients were included in the registry, most of them treated with the Adacolumn™ system. In 69% of patients thiopurine therapy failed to achieve steroid-free clinical remission. Initial clinical remission was obtained in 37% of cases. The initial corticosteroid dose, the number and frequency of apheresis sessions, or the previous failure of thiopurines and/or infliximab did not influence the initial remission rate, but a greater decrease in CRP levels was associated with a higher probability to obtain initial remission. At 6 and 12 months, 41 and 36% of patients were in clinical remission, respectively. Only one serious adverse effect was recorded. In clinical practice, apheresis allows long-term steroid-free clinical remission in up to one third of steroid-dependent UC patients, even in those with prior failure of thiopurines.

Images of colonic real-time tissue sonoelastography correlate with those of colonoscopy and may predict response to therapy in patients with ulcerative colitis

BackgroundReal-time tissue sonoelastography (EG) is a new non-invasive technique that visualizes differences in tissue strain. We evaluated the usefulness of EG in patients with ulcerative colitis (UC) by investigating the association between EG and colonoscopic findings and disease activity.MethodsThirty-seven UC patients undergoing EG and colonoscopy were invited to enroll. EG findings were classified as normal, homogeneous, random, or hard, and colonoscopic findings as normal, mucosal edema and erosion, punched-out ulcer, and extensive mucosal abrasion. Clinical findings were evaluated using clinical activity index (CAI) scores for each patient at colonoscopy.ResultsOn EG, 10 cases were classified as normal, 11 as homogeneous, 6 as random, and 10 as hard. EG findings showed a significant correlation those of colonoscopy (p < 0.001). Seven of 10 (70%) normal-type patients were in the remission phase, while all 6 random-type patients were in the active phase. Among active-phase patients, 4 of 7 (57%) homogeneous-type patients responded to steroid or leukocytapheresis therapy, while 3 of 6 (50%) random-type patients required treatment with cyclosporine. Three of 10 (30%) hard-type patients required colectomy.ConclusionsIn this small series, EG findings reflected colonoscopic findings and correlated with disease activity among patients with UC.

A multicenter study of the efficacy and safety of leukocytapheresis therapy without concomitant systemic steroid treatment in patients with active ulcerative colitis

We conducted a multicenter study to investigate the efficacy of leukocytapheresis (LCAP) without concomitant steroid therapy in active ulcerative colitis (UC) patients. Twenty patients were enrolled. LCAP was performed twice a week for 3 weeks. The results revealed a significant decrease of the Lichtiger’s clinical activity index (CAI) from 11.7 ± 2.6 at baseline to 6.6 ± 4.1 after the therapy. The endoscopic index and serum C-reactive protein levels also decreased significantly after the therapy. Of the 20 patients, 15 (75%) were assessed as responders (CAI ⩽ 4 or ΔCAI ⩾ 3), and 7 (35%) achieved complete remission (CAI ⩽ 4). No serious adverse reactions were encountered. The results suggest that LCAP is an effective and safe option for patients with active UC who had not received systemic steroid treatment.

Tacrolimus: rescue therapy or experimental drug for severe ulcerative colitis? authors’ reply

1. Hart AL, Ng SC. Review article: optimal medical management of acute severe ulcerative colitis. Aliment Pharmacol Ther 2010; 32: 615–27. 2. Yamamoto S, Nakase H, Mikami S, et al. Long-term effect of tacrolimus therapy in patients with refractory ulcerative colitis. Aliment Pharmacol Ther 2008; 28: 589–97. 3. Baumgart DC, Wiedenmann B, Dignass AU. Rescue therapy with tacrolimus is effective in patients with severe and refractory inflammatory bowel disease. Aliment Pharmacol Ther 2003; 17: 1273–81. 4. Ogata H, Matsui T, Nakamura M, et al. A randomized dose finding study of oral tacrolimus (FK506) therapy in refractory ulcerative colitis. Gut 2006; 55: 1255–62. 5. Nakase H, Mikami S, Matsuura M, et al. Rescue therapy with tacrolimus for a patient with severe ulcerative colitis refractory to combination leukocytapheresis and high-dose corticosteroid therapy. Intern Med 2007; 46: 717–20.

The mechanism of the efficiency of Leukocytapheresis on Rheumatoid Arthritis

Several clinical trials revealed that leukocytapheresis (LCAP) was safe and effective therapy for patients with rheumatoid arthritis (RA). In this article, the mechanism of the efficiency of LCAP on RA is reviewed. The counts of activated CD4(+) T cells and CD4(+)CD29(+) T cells were significantly reduced in the synovial fluid after LCAP. Serum tumor necrosis factor alpha, interleukin (IL)-15 and RANTES were significantly reduced, while serum IL-10 significantly increased and this level increased significantly only in the responder group after treatment. P-glycoprotein (Pgp), which causes drug resistance by exclusion of intracellular drugs, expression on Th1 cells following LCAP therapy was significantly decreased after 4 sessions of treatment and 6 months after the last procedure in the responder group. Moreover, remarkable improvements of regulatory T cell (Treg) function were observed in good responders. Our findings suggest that LCAP may cause a reduction of activated T cells from affected joints, down-regulation of Pgp on helper T cells and restoration of Treg function, and that may modify the abnormal cytokine balance. These findings may explain some of the mechanisms by which the articular symptoms are improved by LCAP.

Mucosal healing in patients with ulcerative colitis during a course of selective leukocytapheresis therapy: A prospective cohort study

During active ulcerative colitis (UC), vast numbers of granulocytes, monocytes/macrophages (GM) infiltrate the mucosal tissue and can potentially exacerbate inflammation and injury. Accordingly, we were interested to see if selective depletion of GM by adsorption (GMA) impacts mucosal healing (MH) in UC patients. In all, 124 patients with clinically and endoscopically active UC received 5 or 10 GMA sessions at one or two sessions/week. The endoscopic severity of mucosal inflammation at entry and 1 week after the last GMA session were scored as follows: 0 = normal mucosa and inactive disease; 1 = mild inflammation; 2 = moderate inflammation; 3 = severe inflammation. Likewise, a score 0 or 1 at post-GMA course was defined as MH. At entry the endoscopic severity of the mucosal inflammation was 2 in 100 patients (81%) and 3 in 24 patients (19%). Following the course of GMA, 56 patients (45%) achieved clinical remission (normal stool frequency and no rectal bleeding). Thirty-four of these 56 responders achieved MH; 32 (94%) of the 34 patients with MH had an endoscopic score of 2 (moderate inflammation) at entry. The maintained clinical remission rate was significantly higher in the 34 patients who achieved MH as compared with 22 patients who achieved clinical remission without MH (P = 0.0005). MH is achieved more frequently in patients with moderate than with severe endoscopic severity at entry. Further, patients with MH have a reduced risk of future clinical relapse as compared with patients who achieve remission without MH.

Filtration Leukocytapheresis Therapy Ameliorates Lipopolysaccharide-Induced Systemic Inflammation in a Rat Model

Systemic inflammation, which is associated with various conditions such as sepsis, pneumonia, and trauma, can lead to multiple organ dysfunction syndrome. Systemic inflammation can be life-threatening and is often associated with conditions seen in the intensive care unit. Leukocytes exert a proinflammatory effect and damage various tissues during systemic inflammation. The purpose of this study was to determine whether leukocytapheresis therapy can prevent lipopolysaccharide (LPS)-induced systemic inflammation in a rat model. Male Wistar rats weighing 250 to 300 g were used for all experiments. Rats received an LPS injection, followed 6 h later by filtration leukocytapheresis or mock treatment for 30 min under sevoflurane anesthesia. Systemic inflammation was induced in rats by intravenous LPS injection (7.5 mg/kg) followed by filtration leukocytapheresis. Following blood filtration, we evaluated lung and liver histology, serum cytokine levels, and survival rate of rats for each treatment group. Histologic examination revealed markedly reduced inflammatory injury in lung and liver tissue harvested from rats 24 h after leukocytapheresis therapy compared with mock treatment. LPS-induced tumor necrosis factor (TNF)-α and interleukin (IL)-6 secretion was also inhibited by leukocytapheresis therapy. Moreover, survival was significantly increased in rats treated with high-efficiency leukocytapheresis compared to mock-treated rats (P<0.05). Taken as a whole, our findings indicate that filtration leukocytapheresis therapy protects against LPS-induced systemic inflammation. Therefore, leukocytapheresis shows potential as a new therapy for various systemic inflammatory diseases.

Alteration of CXCR4 Expression and Th1/Th2 Balance of Peripheral CD4-positive T Cells Can Be a Biomarker for Leukocytapheresis Therapy for Patients with Refractory Ulcerative Colitis

Alteration of CXCR4 Expression and Th1/Th2 Balance of Peripheral CD4-positive T Cells Can Be a Biomarker for Leukocytapheresis Therapy for Patients with Refractory Ulcerative Colitis

Effectiveness of leukocytapheresis in suppressing the occurrence of surgical site infections following surgery for ulcerative colitis

Surgical site infections (SSIs) occur more frequently in surgery for patients with ulcerative colitis than in regular colon surgery. We report here on a joint study that was prospectively conducted by six facilities to verify that performing leukocytapheresis (LCAP) therapy immediately following surgery regulates neutrophil activity and acts to suppress the occurrence of SSIs. LCAP was performed using Cellsorba EX with nafamostat mesilate as an anticoagulant; therapy was begun within 2 h postoperatively. Subjects were 143 patients undergoing surgery in cases of ulcerative colitis (LCAP group, 40 patients; control group, 103 patients). 1) With regard to the SSI incidence rate, SSIs occurred in 4 of 37 patients (10.8%) in the LCAP group overall, whereas they occurred in 29 of 103 patients (28.2%) in the control group overall; in the LCAP group, the occurrence of SSIs tended to be suppressed (P = 0.069). With 2-stage surgery in particular, SSIs occurred in the LCAP group in 1 of 28 patients (3.6%) and in the control group in 21 of 86 patients (24.4%); in the LCAP group, the occurrence of SSIs was significantly lower (P = 0.013). The length of postoperative hospitalization was 24.9 +/- 11.1 days for the 36 patients in the LCAP group and 31.2 +/- 14.6 days for the 103 patients in the control group; the length was significantly reduced in the LCAP group (P = 0.018). 2) From pre-surgery to day 1 of hospitalization, the granulocyte elastase level rose both in patients who experienced SSIs and in patients who did not experience them. It remained high in patients who experienced SSIs in comparison with patients who did not experience SSIs and was significantly higher prior to LCAP in particular. 3) While LCAP was being performed, there were adverse events in 5 of 40 patients (12.5%), but these were all transient; it was determined that LCAP presented no problems in terms of safety. LCAP therapy was effective in suppressing the occurrence of SSIs following 2-stage surgery for ulcerative colitis and also reduced the length of postoperative hospitalization.

Leukocytapheresis for the treatment of active pouchitis: a pilot study

Pouchitis is a major long-term complication of ileal pouch-anal anastomosis for ulcerative colitis. The aim of this study is to investigate the efficacy of leukocytapheresis for the treatment of active pouchitis. Eight patients with active pouchitis received leukocytapheresis weekly for 5 weeks in an open-label treatment protocol together with baseline therapy. Patients showed significant improvement in their pouchitis disease activity index scores, from 9.5 (range, 8-10) to 4.0 (range, 2-8) (P < 0.05). Six (75%) of the 8 treated patients achieved remission. No adverse events were observed. Leukocytapheresis therapy could be a new therapeutic strategy for patients with pouchitis after ileal pouch-anal anastomosis for ulcerative colitis. These encouraging results lead us to propose a randomized controlled trial.