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Granulocyte and monocyte adsorptive apheresis for pyoderma gangrenosum

Yuko Higashi,Atsuko Ibusuki,Naoko Baba,Miho Hatanaka,Ko-Ichi Tada,Takuro Kanekura, therapeutic apheresis and dialysis  First published: 09 August 2021

Pyoderma gangrenosum (PG), a chronic aseptic inflammatory skin disease characterized by skin ulcers with elevated and undermined borders, is resistant to conventional therapies. PG is elicited by activated neutrophils and macrophages and is often associated with systemic diseases such as inflammatory bowel disease, rheumatoid arthritis, aortitis syndrome, and hematopoietic disorders. This single-center study assessed the efficacy and safety of selectively depleting myeloid-lineage leukocytes in patients with PG. Patients with PG, aged 20 or over, received 5 or 10 treatment sessions of granulocyte and monocyte adsorption apheresis (GMA), once or twice a week. Treatment efficacy was assessed based on the rate of skin ulcer reduction, the visual analog scale of pain, and the physician’s global assessment of the skin lesions. A complete response (CR) was obtained in eight patients, a nearly complete response (nCR) in three patients, and a partial response (PR) in two patients. In four of the other six, the disease remained stable (SD) and in two we observed disease progression (PD). No severe adverse events were recorded. Our results suggest that GMA is a useful and safe treatment modality for PG.

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Granulocyte and monocyte/macrophage apheresis for the treatment of immune-mediated inflammatory arthropathies: case reports

Carro Martínez AV, Montolio Chiva L, Robustillo Villarino M. Drugs Context. 2021;10:2021-8-5.

Drug therapy of immune-mediated inflammatory arthropathies is not always satisfactory, and there is a risk of adverse events. Granulocyte and monocyte/macrophage apheresis (GMA) is a non-pharmacological therapeutic option that is beneficial and very well tolerated. GMA involves passing blood through a column with cellulose acetate beads to remove increased and activated myeloid lineage cells and improve the cytokine profile. The technique reduces pain and inflammation. We present four clinical reports that illustrate the clinical uses of GMA with the medical device Adacolumn® in patients with different backgrounds and immune-mediated inflammatory arthritis. The results were positive, and no adverse events were reported..

dic.2021-8-5.pdf (

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Leukocytapheresis Therapy for Rheumatoid Arthritis: Results Compared with Control Trial

Jia HuangQian WangYongjing ChengYingjuan ChenMing GaoFeng YangBingyao MuRongwei ZhouCibo Huang,

Altern Ther Health Med. 2020 Jul;26(4):36-42.

Context: Rheumatoid arthritis (RA) is a chronic multisystem autoimmune disease, mainly characterized by synovitis and with symmetrical joint involvement. LCAP therapy for RA patients has been shown to be safe and efficacious in some developed countries for over a decade.

Objective: The study intended to evaluate the efficacy and safety of leukocytopheresis (LCAP) for treatment of rheumatoid arthritis (RA) and to study the influence of treatment on the levels of various serum cytokines. Design: The study was a nonblinded, nonrandomized, controlled trial. Setting: The study took place in the Department of Rheumatology and Immunology at Beijing Hospital at the National Center of Gerontology in Beijing, China. Participants: Participants were 51 patients with RA at the hospital with a 28-joint disease activity score (DAS28) exceeding the 3.20 needed to fulfill the classification criteria of the American College of Rheumatology (ACR). Intervention: Participants were divided into 2 groups. One group (intervention group) received LCAP therapy (n = 20), while the control group (n = 31) received disease-modifying antirheumatic drugs (DMARDs). Patients receiving the LCAP therapy were treated using a Cellsorba column every 5 days for a total of 5 treatments. Outcome measures: Clinical assessment of participants’ symptoms included: (1) a tender-joint count, (2) a swollen-joint count, (3) erythrocyte sedimentation rates (ESR), (4) C-reactive protein levels (CRP), (5) a visual analog scale (VAS) for pain, (6) the DAS28 C-reactive protein (DAS28-CRP) scores, and the Health Assessment Questionnaire Disability Index (HAQ-DI). The study also evaluated participants’ scores for the American College of Rheumatology (ACR) Core Data Set. Serum collected before and after therapy from both groups was analyzed for the levels of bradykinin, serotonin, heat shock protein 70, human CXC-chemokine ligand 16 (CXCL16), prostaglandin E2, and macrophage inflammation protein 1α. Results: At week 4 for participants receiving the LCAP therapy, ACR20, ACR50, and ACR70 were observed in 55%, 30%, and 20% of patients, respectively, compared to 19.4%, 3.2%, and 0% for patients in the control group (P < .05). Also, at week 24 of LCAP therapy, ACR20, ACR50, and ACR70 were observed in 70%, 50%, and 30% of patients, respectively, which was significantly higher than the 25.8%, 12.9%, and 3.2% of patients in the control group (P < .05). The serum levels of CXCL16 and serotonin were significantly reduced in the LCAP group compared with control group. Conclusions: This study indicated that LCAP therapy can significantly decrease RA disease activity and is a safe and effective alternative therapy. LCAP therapy significantly reduced serum CXCL16 and serotonin levels, offering a putative mechanism by which it improves the articular symptoms of RA.

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Recommendations for Therapeutic Apheresis by the Section “Preparative and Therapeutic Hemapheresis” of the German Society for Transfusion Medicine and Immunohematology

Nina Worel 1Behrouz Mansouri Taleghani 2Erwin Strasser 3 Transfus Med Hemother 2019 Dec;46(6):394-406. doi: 10.1159/000503937. Epub 2019 Nov 6.

The section “Preparative and Therapeutic Hemapheresis” of the German Society for Transfusion Medicine and Immunohematology (DGTI) has reviewed the actual literature and updated techniques and indications for evidence-based use of therapeutic apheresis in human disease. The recommendations are mostly in line with the “Guidelines on the Use of Therapeutic Apheresis in Clinical Practice” published by the Writing Committee of the American Society for Apheresis (ASFA) and have been conducted by experts from the DACH (Germany, Austria, Switzerland) region.

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Monocyte subsets involved in the development of systemic lupus erythematosus and rheumatoid arthritis

Sachiko Hirose 1Qingshun Lin 1Mareki Ohtsuji 1Hiroyuki Nishimura 1J Sjef Verbeek 1 , Int Immunol. 2019 Oct 16;31(11):687-696

AbstractMonocytes are evolutionally conserved innate immune cells that play essential roles for the protection of the host against pathogens and also produce several inflammatory cytokines. Thus, the aberrant functioning of monocytes may affect not only host defense but also the development of inflammatory diseases. Monocytes are a heterogeneous population with phenotypical and functional differences. Most recent studies have shown that monocytes are divided into three subsets, namely classical, intermediate and non-classical subsets, both in humans and mice. Accumulating evidence showed that monocyte activation is associated with the disease progression in autoimmune diseases, such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). However, it remains to be determined how monocytes contribute to the disease process and which subset is involved. In this review, we discuss the pathogenic role of monocyte subsets in SLE and RA on the basis of current studies by ourselves and others to shed light on the suitability of monocyte-targeted therapies in these diseases.

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Treatment of inflammatory immunologic disease: Leukocytapheresis for inflammatory immunologic disease (tentative)

Mamoru Watanabe 1Daisuke KubotaMasakazu NagahoriTakanori Kanai , Intern Med
. 2007;46(16):1305-6.

Opinion about effectiviness, safety , number of treated patientes and potential indications of LCAP and GMA.

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Adsorptive monocyte and granulocyte apheresis in the chronic inflammatory illness: ulcerous colitis, Crohn’s disease, rheumatoid arthritis and Behcet syndrome

J. Muñoz, M. Clavo, O. Garcia, D. Reina, A. Vidaller, R. Lafuente & L. I. Massuet

ISBT Science Series (2007) 2, 96–101

There is a strong basis to support the modulators properties of innate immunity of GCAP, although there is a lack of data that explains deeply the interactions between the mechanisms involved. GMA may represent a new therapy that offers not a single pathway effect but a global modulation of the most important pathways involved in innate immune response. Future investigations should elucidate the intimate mechanism of action.’s_disease_rheumatoid_arthritis_and_Behcet_syndrome

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Adsorptive granulocyte/monocyte apheresis for the treatment of refractory rheumatoid arthritis: an open pilot multicentre trial

R Sanmartí 1S MarsalJ ValverdeE CasadoR LafuenteN KashiwagiJ-R Rodriguez-CrosA ErraD ReinaJ Gratacós Rheumatology (Oxford) 2005 Sep;44(9):1140-4. doi: 10.1093/rheumatology/keh701. Epub 2005 May 31.

Objective: To assess the efficacy and safety of adsorptive granulocyte and monocyte apheresis (GCAP) in patients with refractory rheumatoid arthritis (RA). Methods: Patients with active and refractory RA were treated with weekly GCAP sessions using a column filled with acetate beads (Adacolumn) over five consecutive weeks. Clinical assessments and response to therapy were analysed at weeks 5, 7, 12 and 20 in an open multicentre trial. The primary outcome measure of clinical response was 20% improvement in the American College of Rheumatology criteria (ACR20) at week 20. EULAR (European League Against Rheumatism) response criteria, based on the disease activity score for 28 joints (DAS28) and disability using the Health Assessment Questionnaire (HAQ), were also assessed. Results: Of 27 patients, 81.5% were women with mean disease duration of 14.4 yr. The mean number of previous disease-modifying antirheumatic drugs (DMARDs) was 3.7, and 48.1% of patients had previously failed on biologicals. On an intention-to-treat basis, 40.7% of patients achieved an ACR20 and 44.4% a therapeutic EULAR response at week 20. These percentages were 50 and 54.5% in 22 patients who completed the trial. In the 10 completers who had previously failed on biologicals, an ACR response was achieved in four patients (ACR20, two; ACR50, one; ACR70, one). A significant decrease was recorded in different ACR response components, including the tender joint and swollen joint counts, pain score and patient and physician global disease assessments, as well as the DAS28 index; most of them improved after week 5. ESR and CRP, but not the HAQ score, had decreased significantly at week 20. The treatment was well tolerated and only one serious adverse event related to the study procedure was documented (sepsis due to a catheter infection). Conclusions: GCAP treatment led to significant clinical improvement in a subset of patients with RA who had failed to respond to DMARDs or biologicals. Further large, placebo-controlled studies are warranted to fully assess the therapeutic value of GCAP for refractory RA.

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Granulocyte apheresis for pouchitis with arthritis and pyoderma gangrenosum after restorative proctocolectomy for ulcerative colitis: a case report

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Granulocyte adsorptive apheresis for leg ulcers complicated by rheumatoid arthritis: a report on three successfully treated cases

Shinya Mori MD,Masakazu Nagashima MD,Kazuhiro Yoshida MD,Kouji Yoshino MD,Mikako Aoki MD,Seiji Kawana MD,Ichiro Hirata BSc,Abby Saniabadi PhD, Shinichi Yoshino MD, International journal of Dermatology First published: 06 April 2004

GMA, which depletes activated neutrophils and monocytes/macrophages, appears to be effective for inflammatory skin ulcers which do not respond to conventional medications.

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