Leukocytapheresis Sessions Research Articles

Combination of ibrutinib and venetoclax followed by Chimeric Antigen Receptor T-cell therapy in the first line of treatment in an elderly patient with mantle cell lymphoma with hyperleukocytosis and mutation in the TP53 gene

Introduction. The tactics of therapy for elderly comorbid patients with mantle cell lymphoma with unfavorable prognosis factors (complex karyotype, 17p13 deletion, mutations in the TP53 gene) have not been developed. The use of intensive chemotherapy regimens and transplantation of allogeneic hematopoietic stem cells (allo-HSCT) is impossible due to severe comorbidity in elderly patients. A rational approach is the use of a combination of ibrutinib and venetoclax. As an alternative to allo-HSCT, a new option for elderly patients with poor prognostic factors is Chimeric Antigen Receptor T-cell therapy (CAR-T) cell therapy.Aim — to present the experience of using ibrutinib and venetoclax with CAR-T-cell therapy in the first line of treatment in an elderly patient with MCL with a mutation in the TP53 gene and hyperleukocytosis.Main findings. Patient M., 68 years old. The examination revealed hyperleukocytosis 978 × 109/L, anemia (55 g/L), thrombocytopenia (30 × 109/L), and splenomegaly 250 × 180 mm. According to the results of laboratory studies, the diagnosis of lymphoma from mantle cells with a complex karyotype, deletion 17p13, 13q14 and mutation p.R248W in exon 7 of the TP53 gene (VAF = 26 %) was verified. For cytoreductive purposes, two sessions of leukocytapheresis and prephase with cyclophosphamide (200 mg/m2) and dexamethasone (10 mg/m2) were performed. From day 3, therapy with ibrutinib 420 mg/day and venetoclax 100 mg/day was started. After 2 days, the leukocytes were 0.7 × 109/L, and the size of the spleen decreased, as a result of which the development of tumor lysis syndrome was noted. As a result of intensive therapy, the patient’s condition stabilized, which allowed him to resume treatment. After 7 days, the number of leukocytes was 2.5 × 109/L, neutrophils — 70 %, platelets — 90 × 109/L, hemoglobin — 95 g/L. According to immunophenotyping, the population of B-lymphocytes was 4 %. According to NGS data, the allelic load of the mutation in the TP53 gene is 0.8 %. The patient underwent anti-CD19 CAR-T-cell therapy and achieved complete remission. Three months after therapy, MRD remains-negative remission and the persistence of CAR-T cells is determined.

Polymorphism of Interleukins and Tumor Necrosis Factor a Genes in Multiple Myeloma Patients with Autologous Hematopoietic Stem Cell Transplantation

Aim. To assess polymorphism value of interleukins (IL6, IL1B, IL10) and tumor necrosis factor α (TNF) genes in multiple myeloma (MM) patients who received autologous hematopoietic stem cell transplantation (auto-HSCT). Materials & Methods. The study enrolled 37 MM patients (15 men and 22 women) aged 38-66 years (mean age 54.5 ± 6.4 years), who received auto-HSCT. After transplantation, partial (PR), very good partial (VGPR), and complete (CR) responses were reported in 11, 7, and 19 patients, respectively. In 23 (62.2 %) patients CD34+ cell collection on the day of the first leukocytapheresis session exceeded the suboptimal level of 2.5 <sup>x</sup> 10<sup>6</sup>/kg. The control group included 236 healthy subjects. Genotyping by PCR with subsequent analysis of restriction fragment length polymorphism of amplified products was performed. To identify between-group differences in genotype distribution, Fisher's exact test with measurements of odds ratio (OR) and р-value was used. Results. The study group of patients was distinguished from the control group by more than twofold increased proportion of homozygous IL1B -31C (OR 2.7; p = 0.029). The proportion of heterozygous -174G/C allelic variant of IL6 gene in the subgroup of patients with CR after auto-HSCT was considerably higher than in patients with VGPR and PR (OR 5.6; p = 0.022). In the subgroup of patients with CD34+ cell collection > 2.5 x 10<sup>6</sup>/kg the proportion of those with IL10 -592C/C genotype was twice as high as in patients with lower CD34+ cell collection (OR 3.9; p = 0.091). Conclusion. The present study confirms the relationship of -31C/T polymorphism in IL1B gene in homozygous state with higher MM risk. It proved the association of -174G/C polymorphism in IL6 gene and -592C/A polymorphism in IL10 gene with the chosen criteria for auto-HSCT efficacy. To precisely clarify the value of variants in the above genes for predicting chemotherapy effect in MM, further studies involving more patients are required.

A multicenter, retrospective, observational study of the clinical outcomes and risk factors for relapse of ulcerative colitis at 1\xa0year after leukocytapheresis

BackgroundExtracorporeal leukocytapheresis (LCAP) is effective for inducing remission of ulcerative colitis (UC). This retrospective observational study aimed to evaluate the clinical outcome at 1 year and identify risk factors for relapse of UC after LCAP.MethodsPatients with active UC treated with LCAP between 2010 and 2012 were enrolled from 54 medical facilities in Japan. Clinical data evaluated at 1 year after the last LCAP session included the incidence of relapse, 1-year cumulative relapse-free rate, risk factors for relapse, and history of re-induction treatment following relapse. Relapse was defined by the addition of treatment to induce remission. The primary endpoint was the 1-year cumulative relapse-free rate. Secondary endpoints were risk factors for relapse and outcomes of re-induction treatment after relapse.ResultsFor 314 patients, the 1-year cumulative relapse-free rate was 63.6%. Following LCAP, a Lichtiger clinical activity index (CAI) of 3 or 4 and high leukocyte count (cut-off value: 7790/mm3) were associated with a greater risk of relapse. Intensive LCAP (≥4 sessions within the first 2 weeks) was associated with favorable long-term outcomes in corticosteroid-refractory patients. The response rate was 85.1% among 30 patients who required re-treatment with LCAP.ConclusionsThe majority of patients (>60%) with UC treated with LCAP achieved clinical remission within 1 year and remained relapse-free. A higher Lichtiger CAI and leukocyte count following LCAP were risk factors for relapse. Re-induction therapy with LCAP was effective for relapse of UC.

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.

Treatment in adult patients with acute myeloid leukemias and hyperleukocytosis at disease onset

To evaluate the efficiency of the treatment policy for patients with acute myeloid leukemia (AML) and hyperleukocytosis (HL), which is aimed at preventing rapid hypercytolysis and massive tumor lysis (cytolysis) syndrome and/or at reducing the degree of the latter at the start of induction polychemotherapy. In 2010 to 2014, the Hematology Research Center, Ministry of Health of Russia, treated 92 patients with AML, out of them 18 patients were found to have white blood cell counts of 100 to 408-10(9)/1 (median, 130-10(9)/l) at the onset of the disease. All the examinees received cytoreductive therapy with hydroxyurea and, in presence of leukostasis and/or leukocytosis (≥150-10(9)/1), with leukocytapheresis. In case of reduced leukocytosis, plasmapheresis was carried out to prevent (treat) cytolysis. Daunorubicin was injected on days 3-5 of the 7+3 induction cycle. The signs of leukostases were detected in more than half of the 18 patients with higher white blood cell counts: 13 (72%) with lung injury, including 5 of them with signs of respiratory distress syndrome, 6 (27.8%) with neurological symptomatology, 7 (38.9%) with disseminated intravascular coagulation syndrome, including 1 with intracranial hemorrhage. Cytoreduction therapy with hydroxyurea (10 mg/kg/day) was performed 1-5 (median 2) days before initiating induction chemotherapy in 17 patients; 9 patients underwent 1-2 (median 2) leukocytapheresis sessions. Sixteen patients received 1-4 (median 2) plasmapheresis sessions prior to and within the first days of the 7+3 treatment regimen. Daunorubicin (60 mg/m2) was administered to 16 patients on days 5-7 of the 7+3 cycle and to 2 patients on days 3-5 of the cycle. There were no signs of severe cytolysis with the development of multiple organ dysfunction in any patient. 50% (9/18) achieved remission after the first 7+3 cycle and 7 more examinees did after the second cycle. Thus, the remission rate was 89%; early mortality was 5.5% (1/18), three-year overall and relapse-free survival rates were 50%. Adequate cytoreductive and accompanying therapies for AML with HL can virtually completely prevent massive tumor cytolysis syndrome and early mortality during the first days of induction chemotherapy.

Therapeutic leukapheresis: 9-year experience in a University Hospital.

Hyperleucocytosis is associated with higher morbidity and mortality related to possible development of leucostasis, tumour lysis syndrome and/or disseminated intravascular coagulation. There is insufficient evidence of the need for leukocytapheresis during early treatment of hyperleucocytosis, and its efficiency remains controversial, although leucoreduction is a measure that can prevent adverse events and death. The aim of this study was to analyse the safety and effectiveness of therapeutic leukocytapheresis and its influence on early mortality in our case series, adjusted to independent mortality risk factors described in the literature. This was a retrospective review (June 2003-June 2012) of procedures carried out for the treatment of hyperleucocytosis at the Haematology and Haemotherapy Service of Miguel Servet University Hospital. The patients' data and technical information were prospectively registered for each leukocytapheresis session. Thirteen patients underwent a total of 27 leukocytapheresis procedures. After an average of two sessions, a statistically significant drop in the initial leucocyte counts was observed (p<0.01), as well as a relevant drop in lactate dehydrogenase levels. The only analytical value statistically related to early mortality in univariate analysis was initial creatinine level greater than 1.2 mg/dL (p=0.012, OR=2.5). Despite the small size and limited homogeneity of our case series, we can conclude that leukocytapheresis is a safe and effective therapeutic measure for leucoreduction in haematological pathologies of any lineage, particularly in patients without acute myeloid leukaemia. Patients with acute myeloid leukaemia had worse outcomes within 6 months of having finished leukocytapheresis sessions, as well as in terms of mean global survival and mean time of mortality. However, global mortality rates were similar in patients with or without acute myeloid leukaemia.

A large-scale, prospective, observational study of leukocytapheresis for ulcerative colitis: Treatment outcomes of 847 patients in clinical practice

Background and aimsLeukocytapheresis is an extracorporeal therapy for ulcerative colitis. However, no large-scale study on leukocytapheresis has been reported. This large-scale, prospective, observational study aimed to evaluate the treatment outcomes of leukocytapheresis for active ulcerative colitis in clinical practice. MethodsPatients with active ulcerative colitis treated with leukocytapheresis using a Cellsorba E column between May 2010 and December 2012 were enrolled from 116 medical facilities in Japan. ResultsA total of 847 patients were enrolled, and 623 were available for efficacy analysis. Out of 847 patients, 80.3% of the patients had moderate to severe disease activity, and 67.6% were steroid refractory. As concomitant medications, 5-aminosalicylic acids, corticosteroids, and thiopurines were administered to 94.8%, 63.8%, and 32.8% of the patients, respectively. In addition, infliximab and tacrolimus were concomitantly used in 5.8% and 12.3%, respectively. Intensive leukocytapheresis (≥4 leukocytapheresis sessions within the first 2weeks) was used in >70% of the patients. Adverse events were seen in 10.3% (87/847), which were severe in only 5 patients (0.6%). Any concomitant medications did not increase the incidence of adverse events. Intensive leukocytapheresis was as safe as the conventional weekly procedure. The overall clinical remission rate was 68.9% (429/623), and the mucosal healing rate was 62.5% (145/232). Clinical remission was achieved more frequently and rapidly in the intensive group than in the weekly group. ConclusionsThis large-scale study indicates that leukocytapheresis, including intensive procedure, is a safe and effective therapeutic option for active ulcerative colitis.

Successful remission induced by plasma exchange combined with leukocytapheresis against refractory systemic juvenile idiopathic arthritis

Systemic juvenile idiopathic arthritis (sJIA) is an inflammatory cytokine-related disorder associated with overproduction of interleukin (IL)-6, IL-1β, and IL-18. Macrophage activation syndrome (MAS) is a critical and lethal complication of sJIA. Therefore, prompt induction of remission in the active phase of sJIA is important for prevention of MAS. However, treatment of corticosteroid-resistant sJIA is still challenging. We propose a new strategy to induce remission in the active phase of sJIA. A 7-year-old boy with new-onset sJIA was treated with oral prednisolone, methylprednisolone pulse therapy, and parenteral cyclosporine, but he continuously showed remittent high fever, arthralgia, skin rash, and elevation of inflammatory markers, including hyperferritinemia. Because of impending MAS, plasma exchange was started, but he was resistant to plasma exchange. Therefore, we combined leukocytapheresis with PE. After five PE and two leukocytapheresis sessions, he finally achieved remission in accordance with a reduction in inflammatory cytokines. Elevated serum tumor necrosis factor-α, interferon-γ, and IL-12 levels returned to normal 10 days after initiating plasma exchange combined with leukocytapheresis, with a reduction in white blood cell count. In conclusion, plasma exchange combined with leukocytapheresis is a new alternative option to induce remission for patients with methylprednisolone pulse therapy- or cyclosporine-refractory sJIA.

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.

A new paradigm in ulcerative colitis: Regulatory T cells are key factor which induces/exacerbates UC through an immune imbalance

Leukocytapheresis (LCAP) appears to remove or inactivate inflammatory cells and to reset immunological responses, resulting to cure responders of ulcerative colitis (UC). The changes of T cell subsets were investigated in UC patients treated with LCAP. Levels of T cell subsets in peripheral blood before and after LCAP were analysed by flow cytometric analysis. Of 20 UC patients, 13 (65%) achieved remission and 2 (10%) showed the improvement of UC symptoms. Ratios of some T cell subtypes such as regulatory T (Treg) cells and memory T cells to CD4+ T cells changed significantly only in responders. Especially, ratio of resting Treg/CD4+ T cells was significantly increased after the first LCAP session, and then one of activated Treg/CD4+ T cells was increased after 2 week. This may lead to the development of a new UC paradigm in which an imbalance in Treg cell subsets triggers the onset and/or exacerbation of UC.

Optimal apheresis treatment volume for the efficacy and safety of leukocytapheresis with cellsorba in patients with active ulcerative colitis

Leukocytapheresis (LCAP) is used as an adjunct therapy for patients with active ulcerative colitis (UC). Although, LCAP is routinely performed at 3,000 mL per session, we were interested to see that if this can be replaced with bodyweight (BW) adjusted volume. In an open label prospective trial, the clinical response to BW adjusted LCAP (BWA-LCAP) was evaluated in 14 patients with active UC. Fourteen demography matched UC patients who had been treated with the routine 3,000 mL LCAP were randomly sampled from our database as a control group. All patients were given 10 weekly LCAP sessions. In the BWA-LCAP group, the processed blood volume (PBV) was set at 30 mL/kg × BW/session. Baseline demographic measures were not significantly different between the two groups. The average PBV in the BWA-LCAP group was 1971.0 ± 330.0 mL, range 1,020-2,460. In both groups, the average UC clinical disease activity index, the endoscopic index, and the concomitant prednisolone dosage were significantly and equally reduced during the course of 10 LCAP. Accordingly, at the end of the trial, no significant difference was seen in any outcome measure between the two groups. However, a significantly higher incidence of adverse event (AE) was observed in the routine 3,000 mL LCAP group as compared with the BWA-LCAP group (P < 0.01). The outcomes of this investigation showed that the therapeutic efficacy of LCAP based on 30 mL/kg × BW is similar to the routine 3,000 mL per session LCAP. However, BWA-LCAP should be favored if one is to see the full potential of LCAP without AE.

S2018 The Processed Blood Volume Per Leukocytapheresis Session in Patients With Ulcerative Colitis

S2018 The Processed Blood Volume Per Leukocytapheresis Session in Patients With Ulcerative Colitis

Leukocytapheresis (LCAP) decreases the level of platelet-derived microparticles (MPs) and increases the level of granulocytes-derived MPs: a possible connection with the effect of LCAP on rheumatoid arthritis

Microparticles (MPs) are believed to play an important role in inflammatory diseases such as rheumatoid arthritis (RA). Leukocytapheresis (LCAP) is one of the options available for the treatment of RA. We analyzed the levels of MPs in RA, by flow cytometry, especially in relation to the effect of LCAP. Twenty female patients with RA were recruited into this study. Six of the 20 patients with RA further received LCAP. Plasma levels of platelet-derived MPs were high in patients with RA and are correlated with disease activity. LCAP significantly improved RA in all six patients. The numbers of platelet-derived MPs significantly decreased after the first session of LCAP, which was probably due to direct removal by LCAP. Mean numbers of platelet-derived MPs after four sessions of LCAP markedly decreased. The numbers of granulocyte-derived MPs, which are suggested to have an anti-inflammatory effect, were markedly increased after the first session of LCAP. These data suggest that removal of platelet-derived MPs and increase of granulocyte-derived MPs are novel mechanisms of LCAP as effective treatment in RA.

Efficacy of High‐Throughput Leukocytapheresis for Rheumatoid Arthritis With a Reduced Response to Infliximab

Infliximab (INF), a tumor necrosis factor-alpha (TNF-alpha) inhibitor, is an effective drug for patients with rheumatoid arthritis (RA). However, some patients receive no clinical benefit, or the agents gradually lose their effect. Five sessions of high-throughput leukocytapheresis (LCAP) were given at a frequency of once a week using a Cellsorba CS-180S to four patients with a reduced response to INF. The clinical response to LCAP was evaluated using the 28-joint disease activity score with C-reactive protein (DAS28-CRP) and with the erythrocyte sedimentation rate (DAS28-ESR). DAS28-CRP decreased significantly from 5.8 +/- 0.6 before LCAP to 3.9 +/- 0.7 (P = 0.0182) at 1-2 weeks after completion of five sessions of LCAP, and DAS28-ESR decreased significantly from 6.4 +/- 0.6 to 4.6 +/- 0.5 (P = 0.0267). Moreover, all patients had a moderate response according to the European League Against Rheumatism (EULAR) response criteria. The effect of LCAP continued for at least 6 months after its completion in all patients, with no changes in any of their concomitant drugs, and the effect was maintained for at least 1 year in three of the four patients. These results indicate that LCAP is a useful treatment for RA patients with a reduced response to INF.

Leukocytapheresis (LCAP) decreases the level of platelet-derived microparticles (MPs) and increases the level of granulocytes-derived MPs: a possible connection with the effect of LCAP on rheumatoid arthritis

Microparticles (MPs) are believed to play an important role in inflammatory diseases such as rheumatoid arthritis (RA). Leukocytapheresis (LCAP) is one of the options available for the treatment of RA. We analyzed the levels of MPs in RA, by flow cytometry, especially in relation to the effect of LCAP. Twenty female patients with RA were recruited into this study. Six of the 20 patients with RA further received LCAP. Plasma levels of platelet-derived MPs were high in patients with RA and are correlated with disease activity. LCAP significantly improved RA in all six patients. The numbers of platelet-derived MPs significantly decreased after the first session of LCAP, which was probably due to direct removal by LCAP. Mean numbers of platelet-derived MPs after four sessions of LCAP markedly decreased. The numbers of granulocyte-derived MPs, which are suggested to have an anti-inflammatory effect, were markedly increased after the first session of LCAP. These data suggest that removal of platelet-derived MPs and increase of granulocyte-derived MPs are novel mechanisms of LCAP as effective treatment in RA.

Feasibility of Five Days of Consecutive Leukocytapheresis for the Treatment of Ulcerative Colitis: A Preliminary Study

Leukocytapheresis (LCAP) has been applied for the treatment of steroid refractory ulcerative colitis (UC). A standard protocol employs one or two sessions of LCAP per week. Our aim was to determine whether five consecutive LCAP sessions can be performed safely and effectively for UC patients. Six patients with moderately active UC were enrolled. The patients received five days of consecutive LCAP in which the processing volume of blood was limited to 1500 mL per session. The hemoglobin levels in each patient gradually decreased, and the platelet count by the fifth session reached half of the value before the first session. The clinical activity index in two patients improved daily, and they went into remission with an improvement in the colonic endoscopic appearance after one week. This preliminary study showed that five consecutive LCAP sessions are safe and feasible for active UC patients. The therapeutic efficacy and suitable patients for this treatment protocol should be confirmed by further studies.

Ratio of Platelet Reduction is an Early Predictive Factor for the Effectiveness of Leukocytapheresis for Ulcerative Colitis Patients

Leukocytapheresis is effective for ulcerative colitis (UC), and both peripheral leukocyte and platelet counts decrease during apheresis. While leukocyte counts increase and overshoot after finishing the apheresis procedure, platelet reduction continues even after apheresis. The aim of this study is to elucidate the impact of the overshoot of leukocyte and continuous platelet reduction on the efficacy of leukocytapheresis for UC. Leukocyte and platelet counts before and one hour after each leukocytapheresis session of 43 UC cases were examined (31 entered remission, but 12 did not). The correlation between the efficacy of leukocytapheresis and leukocyte overshoot or platelet reduction was examined. The average increase ratio of leukocytes in the initial five sessions of the responders was not significantly different from that of the non-responders (95% vs. 92%, P = 0.28). In contrast, the average decrease ratio of platelets in the initial five sessions of the responders was significantly higher than that of the non-responders (34% vs. 27%, P = 0.0041). Moreover, the platelet reduction at the third and fourth apheresis sessions in the responders was remarkably greater than that in the non-responders (33% vs. 20%, P = 0.0018). The efficiency of platelet reduction could be a predictive factor for the efficacy of leukocytapheresis.

A Pilot Study of Leukocytapheresis Efficacy With 1.5 Liter Blood Processing Volume in Patients With Ulcerative Colitis

Standard leukocytapheresis (LCAP) protocols recommend the processing of a 3 L blood volume. In this study, we evaluated the clinical effects of LCAP with 1.5 L of blood processing (1.5L-LCAP) in patients with active ulcerative colitis (UC). Ten patients with moderate to severe UC were enrolled. Their clinical and endoscopic responses, the kinetics of the peripheral blood counts and cytokine responses were evaluated. Clinical and endoscopic effects were assessed using the clinical activity index described by Rachmilewitz, and by Matts' endoscopic classification, respectively. The 1.5L-LCAP induced clinical remission in 8 out of 10 patients (80%). Endoscopic improvement was noted in 6 out of 7 patients (85.7%). Prednisolone (PSL) was used in 8 patients; the PSL dose could be reduced in 6 patients, and weaning was possible in one patient. Adverse effects were not observed during 1.5L-LCAP therapy. During the 1.5L-LCAP session, the leukocyte count reached the minimum at 1.0 L of blood processing, but promptly increased after completion of the session, and reached a maximum after 30 min. Interleukin (IL)-1beta-induced IL-8 and IL-6 secretion by peripheral blood mononuclear cells were both significantly reduced by 1.5L-LCAP therapy. 1.5L-LCAP was clinically effective for active UC patients. Cellular responses induced by 1.5L-LCAP were similar to those induced by a standard LCAP session.

Microarray Analysis of Leukocytapheresis‐induced Changes in Gene Expression Patterns of Peripheral Blood Mononuclear Cells in Patients With Ulcerative Colitis

To elucidate the molecular mechanisms involved in the therapeutic effects of leukocytapheresis (LCAP), we performed microarray analysis for gene expression patterns in peripheral blood mononuclear cells (PBMCs) before and after LCAP therapy in patients with ulcerative colitis (UC). Four patients with UC were enrolled. PBMCs were isolated from peripheral venous blood obtained within 5 min before and after the first session of LCAP therapy. Cells were stimulated with IL-1beta for 12 h, and gene expression patterns were analyzed by an IntelliGene HS Human Expression Chip. The LCAP session reduced various genes, such as proinflammatory cytokines (IL-1alpha, IL-1beta, IL-6, IL-8, TNF-alpha, and IFN-gamma), cytokine receptors (IL-1R and IL-2Ralpha), chemokines, chemokine receptors, and intracellular signal transduction molecules. Genes which had increased after the LCAP session included those regulating anti-inflammatory cytokines and proteins (TGF-beta1 and IL-R antagonist), receptors for anti-inflammatory cytokines (IL-10R and IL-4R), growth factor receptors (IGF-R1, R2) and antioxidant proteins. Total changes in gene expression patterns after LCAP session were a combination of a decrease in pro-inflammatory genes and an enhancement of anti-inflammatory genes. These changes may explain some parts of the mechanisms by which LCAP improves clinical symptoms of UC patients.

Predictive factors of efficacy of leukocytapheresis for steroid-resistant ulcerative colitis patients

Background The effectiveness of leukocytapheresis against ulcerative colitis has been reported. However, the efficacy of this therapy for steroid-resistant ulcerative colitis patients has hardly been examined. Aims The aims of this study are to evaluate the efficacy of leukocytapheresis for steroid-resistant ulcerative colitis patients and to identify clinical factors that predict the efficacy of this therapy for these patients. Methods Clinical factors of 71 steroid-resistant ulcerative colitis patients who underwent leukocytapheresis analysed. Results Of those analysed, 53 (75%) patients showed an initial response to leukocytapheresis. Among cases with initial response, however, only 19 (27%) patients maintained remission for more than 6 months. Steroid-dependent course (Odds ratio = 5.53, 95% confidence interval; 1.24–24.73) and a high C-reactive protein degree (Odds ratio = 1.6, confidence interval; 1.09–2.35) were predictors of initial response to leukocytapheresis. Rapid response, which means remission induction within three leukocytapheresis sessions, was the only predictor of maintenance of remission for more than 6 months after successful leukocytapheresis therapy (odds ratio = 8.01, confidence interval; 1.08–59.37). Conclusions Leukocytapheresis was effective for steroid-resistant ulcerative colitis patients. However, relapse was frequently observed within short periods after the initial response to this therapy. Patients without a rapid response should be treated with alternative or additional therapies.