• adsorptive cytapheresis
• efficacy
• inflammatory bowel diseases
• mechanisms of action
• safety
• side effects
• ulcerative colitis

• Humans
• Aged
• Colitis, Ulcerative/therapy
• Biosimilar Pharmaceuticals/therapeutic use
• Cytapheresis
• Adrenal Cortex Hormones/therapeutic use
• Remission Induction
• Tumor Necrosis Factor-alpha
• Treatment Outcome
• Granulocytes
• Monocytes

• apoptotic neutrophils
• inflammatory bowel disease
• interleukin-10
• mucosal lesions
• myeloid lineage leukocytes
• pediatrics and adolescents
• regulatory b-cells
• therapeutic granulomonocytapheresis

• Adacolumn
• Crohn’s disease
• Ulcerative colitis
• adsorptive granulocyte and monocyte apheresis
• biomarkers
• inflammatory bowel disease

• gastroenterology
• haematology
• immunology
• inflammatory bowel disease

• Blood Component Removal
• Colitis, Ulcerative/therapy
• Granulocytes
• Humans
• Monocytes
• Remission Induction

• Grant of the Hungarian Science Foundation
• Economic Development and Innovation Operative Programme Grant
• Human Resources Development Operational Programme Grants

The etiology and pathogenesis of inflammatory bowel disease (IBD), including ulcerative colitis and Crohn’s disease, are not fully understood so far. Therefore, IBD still remains incurable despite the fact that significant progress has been achieved in recent years in its treatment with innovative medicine. About 20 years ago, selective granulocyte and monocyte apheresis (GMA) was invented in Japan and later approved by the Japanese health authority for IBD treatment. From then on this technique was extensively used for IBD patients in Japan and later in Europe. Clinical trials from Japan and European countries have verified the effectiveness and safety of GMA therapy in patients with IBD. In 2013, GMA therapy was approved by China State Food and Drug Administration for therapeutic use for the Chinese IBD patients. However, GMA therapy has not been extensively used in China, although a few clinical studies also showed that it was effective in clinical and endoscopic induction of remission in Chinese IBD patients with a high safety profile. This article reviews past history, present clinical application as well as the future prospective of GMA therapy for patients with IBD.

• Inflammatory bowel disease
• Ulcerative colitis
• Crohn’s disease
• Granulocyte and monocyte apheresis
• Therapy
• Efficacy

• Crohn’s disease
• anti-inflammatory
• biologics
• inflammatory bowel diseases
• natural products drugs
• small molecule drugs
• ulcerative colitis

• adsorptive granulocytes and monocytes apheresis
• complement activation fragments
• granulomonocytapheresis
• inflammatory bowel disease
• myeloid lineage leucocytes
• treating inflammatory bowel disease without drugs

• Ambulatory Care/standards
• Child
• Child Nutritional Physiological Phenomena
• Colitis, Ulcerative/diagnosis
• Colitis, Ulcerative/therapy
• Europe
• Female
• Humans
• Male
• Societies, Medical

• Ulcerative colitis
• devices
• granulocyte/monocyte adsorptive apheresis
• inflammatory bowel disease
• large intestine

• Adacolumn granulomonocytapheresis
• Crohn’s disease
• Inflammatory bowel disease
• adolescents
• myeloid lineage leukocytes
• pediatrics
• ulcerative colitis

• Ulcerative colitis
• adacolumn
• apheresis

AIM: To investigate efficacy and safety for granulocyte, monocyte apheresis in a population of pediatric patients with ulcerative colitis.

METHODS: The ADAPT study was a prospective, open-label, multicenter study in pediatric patients with moderate, active ulcerative colitis with pediatric ulcerative colitis activity index (PUCAI) of 35-64. Patients received one weekly apheresis with Adacolumn^® granulocyte, monocyte/macrophage adsorptive (GMA) apheresis over 5 consecutive weeks, optionally followed by up to 3 additional apheresis treatments over 3 consecutive weeks. The primary endpoint was the change in mean PUCAI between baseline and week 12; the secondary endpoint was improvement in PUCAI categorized as (Significant Improvement, PUCAI decrease of ≥ 35), Moderate Improvement (PUCAI decrease of 20 < 35), Small Improvement (PUCAI decrease of 10 < 20) or No change (PUCAI decrease of < 10).

RESULTS: Twenty-five patients (mean age 13.5 years; mean weight 47.7 kg) were enrolled. In the intention-to-treat set (ITT), the mean value for PUCAI improvement was 22.3 [95%CI: 12.9-31.6; n = 21]. In the per-protocol (PP) set, the mean improvement was 36.3 [95%CI: 31.4-41.1; n = 8]. Significant Improvement was recorded for 9 out of 20 patients (45%); 5 out of 20 patients (25%) had Moderate Improvement and one patient (5%) had No Change in PUCAI score at week 12. In the PP set, six out of eight patients (75%) showed Significant Improvement; and in two out of eight patients (25%) Moderate Improvement was recorded. The endoscopic activity index (EAI) decreased by 3 points on average. Seven (7) out of 21 (33%) patients in ITT and 4 out of 8 (50%) patients in PP have used steroids during the clinical investigation. The mean steroid dosage for these patients in the ITT set decreased from a mean 12.4 mg to 10 mg daily on average from Baseline to week 12.

CONCLUSION: Adacolumn^® GMA apheresis treatment was effective in pediatric patients with moderate active Ulcerative Colitis. No new safety signals were reported. The present data contribute to considering GMA apheresis as a therapeutic option in pediatric patients having failed first line therapy.

• Granulocyte-monocyte apheresis
• Pediatric
• Ulcerative colitis
• Inflammatory bowel disease
• Therapy
• Steroids
• Clinical trial

• Adolescent
• Blood Component Removal/adverse effects
• Child
• Colitis, Ulcerative/therapy
• Female
• Granulocytes
• Humans
• Macrophages
• Male
• Monocytes
• Prospective Studies

• Crohn's disease
• Granulocyte monocyte adsoption apheresis
• Inflammatory bowel disease
• Ulcerative colitis

Granulocyte and monocyte adsorptive apheresis (GMA) has shown efficacy in patients with active Crohn’s disease (CD). However, with routine weekly therapy, it may take several weeks to achieve remission. This study was performed to assess clinical efficacy and safety of intensive GMA in patients with active CD.

In an open-label, prospective, randomized multicentre setting, 104 patients with CD activity index (CDAI) of 200 to 450 received intensive GMA, at two sessions per week (n = 55) or one session per week (n = 49). Clinical remission was defined as a CDAI score <150. Patients in each arm could receive up to 10 GMA sessions. However, GMA treatment could be discontinued when CDAI decreased to <150 (clinical remission level).

Of the 104 patients, 99 were available for efficacy evaluation as per protocol, 45 in the weekly GMA group, and 54 in the intensive GMA group. Remission was achieved in 16 of 45 patients (35.6 %) in the weekly GMA and in 19 of 54 (35.2 %) in the intensive GMA (NS). Further, the mean time to remission was 35.4 ± 5.3 days in the weekly GMA and 21.7 ± 2.7 days in the intensive GMA (P = 0.0373). Elevated leucocytes and erythrocyte sedimentation rate were significantly improved by intensive GMA, from 8005/μL to 6950/μL (P = 0.0461) and from 54.5 mm/hr to 30.0 mm/hr (P = 0.0059), respectively. In both arms, GMA was well tolerated and was without safety concern.

In this study, with respect to remission rate, intensive GMA was not superior to weekly GMA, but the time to remission was significantly shorter in the former without increasing the incidence of side effects. UMIN registration # 000003666.

The online version of this article (doi:10.1186/s12876-015-0390-3) contains supplementary material, which is available to authorized users.

• Anastomosis ileoanal con reservorio
• Cirugía
• Colitis ulcerosa
• Inmunosupresor
• Tratamiento

• Colitis, Ulcerative/complications
• Colitis, Ulcerative/diagnosis
• Colitis, Ulcerative/therapy
• Combined Modality Therapy
• Disease Progression
• Europe
• Gastrointestinal Agents/therapeutic use
• Humans
• Ileostomy
• Immunosuppressive Agents/therapeutic use
• Induction Chemotherapy
• Maintenance Chemotherapy
• Proctocolectomy, Restorative
• Severity of Illness Index

Ulcerative colitis and Crohn’s disease are the major phenotypes of the idiopathic inflammatory bowel disease (IBD), which afflicts millions of individuals throughout the world with debilitating symptoms, impairing function and quality of life. Current medications are aimed at reducing the symptoms or suppressing exacerbations. However, patients require life-long medications, and this can lead to drug dependency, loss of response together with adverse side effects. Indeed, drug side effects become additional morbidity factor in many patients on long-term medications. Nonetheless, the efficacy of anti-tumour necrosis factors (TNF)-α biologics has validated the role of inflammatory cytokines notably TNF-α in the exacerbation of IBD. However, inflammatory cytokines are released by patients’ own cellular elements including myeloid lineage leucocytes, which in patients with IBD are elevated with activation behaviour and prolonged survival. Accordingly, these leucocytes appear logical targets of therapy and can be depleted by adsorptive granulocyte/monocyte apheresis (GMA) with an Adacolumn. Based on this background, recently GMA has been applied to treat patients with IBD in Japan and in the European Union countries. Efficacy rates have been impressive as well as disappointing. In fact the clinical response to GMA seems to define the patients’ disease course, response to medications, duration of active disease, and severity at entry. The best responders have been first episode cases (up to 100%) followed by steroid naïve and patients with a short duration of active disease prior to GMA. Patients with deep ulcers together with extensive loss of the mucosal tissue and cases with a long duration of IBD refractory to existing medications are not likely to benefit from GMA. It is clinically interesting that patients who respond to GMA have a good long-term disease course by avoiding drugs including corticosteroids in the early stage of their IBD. Additionally, GMA is very much favoured by patients for its good safety profile. GMA in 21^st century reminds us of phlebotomy as a major medical practice at the time of Hippocrates. However, in patients with IBD, there is a scope for removing from the body the sources of pro-inflammatory cytokines and achieve disease remission. The bottom line is that by introducing GMA at an early stage following the onset of IBD or before patients develop extensive mucosal damage and become refractory to medications, many patients should respond to GMA and avoid pharmacologics. This should fulfill the desire to treat without drugs.

• Inflammatory bowel disease
• Myeloid lineage leucocytes
• Adsorptive granulocytes/monocytes apheresis
• Corticosteroid sparing effect
• Complement activation fragments
• Treating inflammatory bowel disease without drugs

• Colitis, Ulcerative/blood
• Colitis, Ulcerative/diagnosis
• Colitis, Ulcerative/economics
• Colitis, Ulcerative/immunology
• Colitis, Ulcerative/therapy
• Colonoscopy
• Cost-Benefit Analysis
• Crohn Disease/blood
• Crohn Disease/diagnosis
• Crohn Disease/economics
• Crohn Disease/immunology
• Crohn Disease/therapy
• Cytokines/metabolism
• Health Care Costs
• Humans
• Inflammation Mediators/metabolism
• Leukapheresis/economics
• Leukapheresis/methods
• Predictive Value of Tests
• Treatment Outcome

• Dose intensification
• Double filters
• Granulocyte
• Platelet count
• Rachmilewitz index
• Ulcerative colitis
• monocyte apheresis

• Corticosteroids
• Granulocyte and monocyte adsorption apheresis
• Ulcerative colitis

• Crohn's Disease
• Granulocytapheresis
• Steroid-dependence
• Steroid-resistance
• Ulcerative Colitis

Granulocyte-monocyte apheresis is a relatively new therapy that has been proposed, sometimes with controversial results, for the treatment of inflammatory bowel disease, particularly ulcerative colitis. The aim of the present study was to perform a thorough review of the literature on the application of this type of treatment in ulcerative colitis and discuss the results, in order to provide an opinion on its use which is shared by the involved experts. The review of the literature was performed by searching PubMed with appropriate key words. The results obtained suggest that the major role for this treatment at this moment is for those patients with steroid dependency or with major contraindications to use of steroids. However, promising, albeit very preliminary, results have also been observed in steroid-naïve subjects, and this is of particular interest in consideration of the safety profile of this therapeutic method. As such, the Adacolumn may prove useful in specific subgroups of patients. Future phenotypic, genotypic, and molecular characterization of patients with inflammatory bowel disease might prove useful in defining better those subjects who might benefit most from this treatment modality.

• apheresis
• guidelines
• inflammatory bowel disease
• ulcerative colitis

• Adult
• Colitis, Ulcerative/drug therapy
• Colitis, Ulcerative/therapy
• Databases, Factual
• Female
• Follow-Up Studies
• Humans
• Kaplan-Meier Estimate
• Leukapheresis/methods
• Male
• Remission Induction
• Spain
• Steroids/therapeutic use
• Treatment Outcome