Cytapheresis practice: recommendations of New York Cytapheresis Task Force.
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Treatment with cytapheresis for antineutrophil cytoplasmic antibody-associated renal vasculitis and its effect on anti-inflammatory factors.
To evaluate the efficacy of cytapheresis for the treatment of rapidly progressive glomerulonephritis (RPGN) caused by myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA)-associated vasculitis, the renal prognosis and the mortality rate at 1 year after treatment were compared between a Cytapheresis Group and a Steroid Pulse Group. The Cytapheresis Group included 10 patients who were treated with cytapheresis and oral corticosteroids. Five had granulocytapheresis with the Adacolumn (Japan Immuno Research Laboratories Co. Ltd, Takasaki, Japan) and the remaining five had leukocytapheresis with the leukocyte removal filter, Cellsorba (Asahi Medical Co. Ltd, Tokyo, Japan). The Steroid Pulse Group was comprised of 12 patients who were treated with methylprednisolone pulse therapy and oral corticosteroids. In the Cytapheresis Group, renal function recovered in 70% of the patients and the mortality rate was 10%. In the Steroid Pulse Group, renal function recovered in 66.7% and the mortality rate was 33.3%, with infection as the cause of death. Total doses of corticosteroids converted to prednisolone dose during a 1 month period, ranged from 280 mg to 1226 mg in the Cytapheresis Group. On the other hand, these dosages ranged from 2375 mg to 8380 mg in the Steroid Pulse Group. These results indicated that the mortality rate by infection could be reduced by adding cytapheresis therapy. Concerning the mechanism of cytapheresis, anti-inflammatory factors such as soluble tumor necrosis factor receptor, and interleukin-10 reduced after cytapheresis. These changes might be responsible for the efficacy of cytapheresis. In conclusion, cytapheresis is thought to be one of the effective treatments for RPGN caused by MPO-ANCA-associated vasculitis, reducing the levels of anti-inflammatory factors.
Adrenal Cortex Hormones↗
In vitro and in vivo evaluation of Adacolumn cytapheresis in healthy subjects.
Adacolumn is a medical device for adsorptive cytapheresis. It has been developed for selective adsorption of granulocytes and monocytes from peripheral blood of patients with immune disorders, such as autoimmune diseases and chronic inflammatory diseases. A double blind sham-controlled crossover study design was used in order to evaluate in vivo biological responses of leukocytes as well as biocompatibility during and after Adacolumn cytapheresis in healthy volunteers. In addition, experiments were undertaken to further evaluate leukocyte reactions to Adacolumn carrier (G-1: cellulose diacetate) beads in vitro. Six healthy volunteers, 4 males and 2 females, with a mean age of 26.7 years were randomly assigned to one of the two treatment arms in a crossover fashion. Three subjects received a single Adacolumn treatment, followed by a single sham treatment at an interval of 7 days. The other three subjects received the two treatments in reverse order. All subjects were followed up 7 days after the last treatment. Additionally, in vitro investigations were carried out using blood from the healthy donors to examine the effect of G-1 beads on granulocyte functions. In vitro exposure of human peripheral blood to G-1 beads caused downregulation of L-selectin expression and upregulation of Mac-1 expression on granulocytes, leading to a marked reduction of adhesive capacity of granulocytes to endothelial cells. The exposure also led to decreased granulocyte chemotactic activity to IL-8. The number of granulocytes and monocytes clearly decreased during Adacolumn cytapheresis. Granulocytes showed marked phenotypic changes of L-selectin(Low) and Mac-1(Hi) after passing through Adacolumn in vivo. Expression of TNF-alpha and chemokine receptors was downregulated. In addition, TNF-alpha and IL-1beta producing capacity of peripheral blood leukocytes was decreased after Adacolumn cytapheresis and these changes lasted even one week after the cytapheresis. The level of complement fragments, C3a and C5a, increased, while bradykinin concentration did not change during Adacolumn cytapheresis. Exposure of human peripheral blood to G-1 beads, both in vitro and in vivo, caused a significant reduction of adhesive capacity and proinflammatory cytokine producing capacity of peripheral blood leukocytes. Such changes were not observed after sham apheresis. Despite complement activation, tolerability of Adacolum cytapheresis was not influenced. These findings may at least partly explain the beneficial effect of Adacolumn cytapheresis in the treatment of autoimmune diseases.
Adult↗
Cytapheresis for the treatment of myeloperoxidase antineutrophil cytoplasmic autoantibody-associated vasculitis: a pilot study of 21 patients.
Twenty-one patients with myeloperoxidase-antineutrophil cytoplasmic autoantibody (MPO-ANCA)-associated vasculitis were treated using cytapheresis. Of these, 17 were treated for glomerulonephritis and four were treated for pulmonary hemorrhage. The overall survival rate was 85.7% with a follow-up duration of 24.0 +/- 13.8 months. In the 17 patients with MPO-ANCA-associated glomerulonephritis, pretreatment creatinine was 3.2 +/- 1.6 mg/dL, and renal function recovered in 76.5%. Pulmonary hemorrhage was ameliorated in all four patients. Abdominal pain occurred in three of the 21 patients but symptoms resolved soon after the cytapheresis procedure was completed. No other adverse effects occurred during cytapheresis. From these results, cytapheresis can be considered a safe and effective treatment for MPO-ANCA-associated vasculitis. As for the mechanism of its action, soluble tumor necrosis factor receptor 1 (sTNFR), sTNFR2 and interleukin 1 receptor antagonist were elevated soon after cytapheresis and those levels 2 h after the cytapheresis procedure were higher than before the procedure in some cases. These elevations might be related to the efficacy of cytapheresis.
Aged↗
Current topics on cytapheresis technologies.
Cytapheresis has been investigated recently for the treatment of autoimmune related diseases, such as rheumatoid arthritis (RA), inflammatory bowel disease (IBD), multiple sclerosis, and so on. A large number of physicians have indicated that patients with autoimmune diseases respond to cytapheresis treatment. The effective mechanism of cytapheresis for immune disorders is still controversial. However, the removal of the leukocyte including granulocyte, lymphocyte, and monocyte may play a crucial role in correcting imbalance of the immune system. A session of cytapheresis including leukocytapheresis (LCAP) and granulocytapheresis (GCAP) may not create a sufficient amount of cell removal for the human body. However, the cell removal can be a trigger of the immunomodulation as the treatment for immune disorder. Furthermore, not only cell removal but also reaction by blood contacting with medical device materials may play a role as an immunomodulation for immune disorders. This review introduces current cytapheresis technologies and attempts to elucidate the effective mechanism of cytapheresis for immune disorders, focused on LCAP and/or GCAP for RA or IBD.
Arthritis, Rheumatoid↗
Concurrent comparison of the safety of paid cytapheresis and volunteer whole-blood donors.
BACKGROUND: Historically, paid blood donors were found to transmit hepatitis at higher rates than volunteers. In those older studies, paid donors frequently were recruited from prisons or slum areas--a finding consistent with the belief that monetary payment in itself did not necessarily lead to the high-risk status of commercial blood. Instead, it was the population base from which the donors were recruited that was important. STUDY DESIGN AND METHODS: Today, cytapheresis donors are in great demand. Because payment is one incentive that might entice donors to undertake the increased commitment of repeated cytapheresis donation, the results were studied of infectious disease history and laboratory testing performed concurrently in 917 volunteer whole-blood donors and 1240 paid cytapheresis donors, who were enrolled in distinct programs at the DeGowin Blood Center from October 7, 1987, through November 30, 1990. RESULTS: When first, repeat, and overall donations made by these donors were evaluated separately, paid cytapheresis donors were found to exhibit no increase in infectious disease history or test results beyond those of volunteer whole-blood donors. CONCLUSION: Thus, paid cytapheresis donors, when managed within a formal program, should not necessarily be presumed to be more dangerous than volunteers, from an infectious disease aspect. However, definitive proof of safety (comparison of transfusion-transmitted infection rates in two groups of patients receiving blood components exclusively from either paid cytapheresis or volunteer donors) was not pursued by long-term follow-up studies.
Blood Donors↗
[Sezary syndrome treated by cytapheresis. Short and long-term results].
INTRODUCTION: Sezary syndrome is usually resistant to most treatments. The aim of this work was to evaluate short and long-term results of cytapheresis in patients with Sezary syndrome. PATIENTS AND METHODS: Twenty-two patients with Sezary syndrome were included in the study (13 men, 9 women, man age 58 +/- 35.4 years). The mean duration of Sezary syndrome before cytapheresis was 6.5 +/- 2 months. Extra-cutaneous involvement was observed in 16 of the patients. Each patient underwent 33 +/- 63 cytapheresis sessions (total number = 685). Complete remission in "responders" was defined as the absence of clinical signs and Sezary cells < 1,000/mm3. In "non responders" partial remission was defined as incomplete regression of clinical signs and Sezary cells > 1,000/mm3 and failure as lack of improvement or worsened clinical situation. RESULTS: Complete remission was obtain in 10/22 patients (45.5 p. 100), partial remission in 4/22 (18 p. 100) and failure in 8/22 (36.5 p. 100). There was no significant difference between responders and non-responders for age, duration of the Sezary syndrome before cytapheresis, the number of sessions, extracutaneous involvement, or another associated treatment. In the responders, mean survival was 90 +/- 42 months. Two patients were alive at 5 years and 1 at 10 years. In the non responders, mean survival was 8 +/- 1.4 months and median survival was 11 months. CONCLUSION: There was no significant evidence suggesting a difference between responders and non-responders. Nevertheless, mean survival was longer in patients who had achieved complete remission. Cytapheresis is thus justified for the treatment of patients with Sezary syndrome.
Adult↗
Therapeutic cytapheresis for inflammatory bowel disease.
Cytapheresis therapy has recently been investigated as a treatment for several diseases, especially autoimmune related diseases such as rheumatoid arthritis, systemic lupus erythematosus, and inflammatory bowel disease. The removal of leukocyte components has been performed by the centrifugal method; however, using fiber technology or column technology, leukocyte components can be removed simply, and these technologies are more effective than the centrifugal method in removing numbers of cells. Each of 3 types of leukocytapheresis methods removes a different kind of cell in its therapeutic principle. Thus, if we understand what kind of cells should be removed, we can choose the best method for removing leukocytes. For this reason, the authors propose an international standard for unifying names. The therapy that makes use of a centrifuge to selectively remove about 40% of neutrophils and more than 60% of lymphocytes may be called a lymphocyte removal therapy, lymphocytapheresis (LCA). Using cellulose acetate beads in a G-1 granulocyte removal column, granulocytes and monocytes are removed but not lymphocytes, so we suggest calling this granulocytapheresis (GCAP). In addition, using a leukocyte removal filter, the Cellsorba leukocyte removal filter, 99% of both granulocytes and monocytes and about 70% of lymphocytes are removed. We propose calling this leukocytapheresis (LCAP). In the near future, we hope that we will be able to select one of these methods for cytapheresis for each disease pathogenesis or cellular immune abnormality. Presently, a lot of research is on-going to analyze how cytapheresis is effective for the immune related diseases. The mechanism of cytapheresis will be clarified by investigators. We strongly believe that cytapheresis therapies offer good news to those patients suffering from incurable diseases as well as their physicians.
Humans↗
Critical care by cytapheresis.
We report our experience of cytapheresis using a nonwoven polyester fiber filter to treat critical states of immune diseases. In 7 critical states of ulcerative colitis (UC), cytapheresis was effective in improving symptoms of UC. Administration of steroids was important in some cases. In 3 cases of renal transplantation, cytapheresis was also effective in controlling rejection. IgA nephropathy of transplanted cases was well controlled. Furthermore, an original disease such as focal segmental glomerulosclerosis (FCGS) in a transplant patient was well treated by extracorporeal immune modulation of the cytapheresis.
Adult↗
Pilot clinical study of Adacolumn cytapheresis in patients with systemic lupus erythematosus.
The aim of this study is to investigate the clinical effects of cytapheresis using the Adacolumn system (selective removal of circulating monocytes and granulocytes by means of an extracorporeal type column) in patients with active systemic lupus erythematosus (SLE). An open uncontrolled multicenter pilot study was conducted in 18 SLE patients who were showing a SLEDAI score of 8 or more under conventional medication. Patients with lupus nephritis (>class 1, WHO classification) were excluded. Extracorporeal cytapheresis with the Adacolumn system was administered once a week for five consecutive weeks. The efficacy of the treatment was evaluated using the SLEDAI for 10 weeks after the first cytapheresis session. The median SLEDAI decreased from 16 at baseline to six at week 11 (10 weeks after the first apheresis) (p<0.001). Significant improvements in musculoskeletal and dermal systems were observed. Arthritis and alopecia were present in 14 and nine patients at baseline and this number decreased to five and one patients, respectively by week 11. Three mild and one moderate adverse events out of the 42 reported events were judged 'probably related' to the treatment; no serious adverse events were reported. Selective removal of monocytes and granulocytes from the blood in an extracorporeal circulation system was associated with clinical improvement in this small series of patients with SLE. Since this approach seems not to have the disadvantages of pharmacological immunosuppression, further controlled studies of Adacolumn cytapheresis are warranted in SLE.
Adult↗
Effects of cytapheresis on cell cycle distribution of peripheral blood and bone marrow cells in some hematological malignancies.
Feulgen-DNA cytophotometry and 3H-thymidine autoradiography were used to evaluate therapeutic cytapheresis effects on cell cycle distributions of peripheral blood leukemic cells in 15 acute leukemia, 5 CML and 8 CLL patients and of bone marrow erythroblasts in 18 PV patients. Both individual cytapheresis procedures and a long-term program of cytapheresis altered cell cycle distributions and biochemistry which may be summarized as follows: An increase in percentage of cells in S-phase (acute leukemia, CML); a decrease in the differences between values of S-cell number obtained by cytophotometry and autoradiography (acute leukemia, CML, PV); a decrease in some cases in enlarged fraction of cells in G2 (blast crisis of CML, PV); an activation of G0----G1 transition and an increase in the PAS-positive lymphocyte fraction in CLL patients. An apparent increase of blasts in S-phase was found after a pheresis in acute leukemia patients who responded to subsequent chemotherapy. In "nonresponders", a pheresis had no effect on cell cycle distributions. The results of the study demonstrate that despite the wide variability of individual responses, cytapheresis activates cell proliferation and metabolic processes in patients with hematological malignancies.
Blast Crisis↗
Cytapheresis for the treatment of myeloperoxidase antineutrophil cytoplasmic antibody-associated vasculitis: report of five cases.
To minimize the adverse effects of high-dose administration of steroids and cyclophosphamide in patients with myeloperoxidase (MPO) antineutrophil cytoplasmic antibody (ANCA), granulocytapheresis (GCAP) or leukocytapheresis (LCAP) was performed to reduce inflammation. Four patients with rapidly progressive glomerulonephritis (RPGN) and one patient with pulmonary hemorrhage due to MPO-ANCA-associated vasculitis were treated by cytapheresis. The prednisolone (PSL) dose was 0.28 +/- 0.15 mg/kg/day (mean +/- SD) (range 0.18-0.50 g/kg/day). In the 4 RPGN patients, the peak serum creatinine level was 3.7 +/- 1.9 mg/dl (range 1.7 to 5.6 mg/dl). GCAP was performed in 3 RPGN patients and in 1 pulmonary hemorrhage patient. LCAP was performed in 1 RPGN patient. In the 4 RPGN patients, renal function improved after combined therapy with cytapheresis and corticosteroids. In the pulmonary hemorrhage patient, evidence of pulmonary hemorrhage on chest computed tomography scanning diminished after combined therapy with cytapheresis and corticosteroids. Cytapheresis, when combined with a low-dose or intermediate-dose PSL regimen, is effective in the treatment of ANCA-associated vasculitis.
Aged↗
Evaluation of granulocyte-releasing products and chemiluminescence during cytapheresis.
During the procedures of centrifugation leukapheresis and plateletpheresis, donors occasionally experience adverse clinical reactions. The possibility of whether the activation of granulocytes and the subsequent release reactions, which may have been triggered by this extracorporeal circuit, were responsible for these adverse effects was evaluated. Six blood samples were obtained at set intervals during cytapheresis. Of these samples, four were taken directly from the donor. The remaining two were drawn from the efferent lines, i.e., those which return blood from the cytapheresis machine to the donor. Reactive oxygen species produced by granulocytes were measured by chemiluminescence (CL) using microamounts of whole blood or isolated granulocytes. Furthermore, secreted granulocyte products such as neutral proteinase elastase, which is present in plasma in a complex with alpha-1-proteinase inhibitor (E-alpha-1-PI), and lysosomal beta-glucuronidase were examined. A complete blood cell count and the values of hemoglobin, hematocrit, lactate dehydrogenase, protein, albumin, and proteinase inhibitors such as alpha-2-macroglobulin and alpha-1-proteinase inhibitor were also determined. Clinical chemical and cytologic values, with the exception of those for E-alpha-1-PI, were 10 to 17 percent lower than values before apheresis. These results can be attributed to inherent plasma volume expansion. Reduced CL was observed on the stimulation of phagocytes in the whole blood assay, as well as with stimulated granulocytes. Unstimulated granulocytes, on the other hand, showed an increased native CL. These data do not indicate a cytapheresis-mediated activation of the oxidative metabolism of granulocytes, and the concomitant discharge of proteolytic enzymes remains, therefore, of no clinical importance.
Blood Cell Count↗
Therapeutic cytapheresis using the Fenwal CS-3000 blood cell separator.
20 patients, 16 with acute or chronic leukemia and 4 with thrombocytosis, underwent 47 therapeutic cytapheresis procedures using the Fenwal CS-3000 cell separator. 16 of the 20 patients had acute clinical signs or symptoms secondary to high circulating cell counts; 14 showed symptomatic improvement following cytapheresis. An average of 2.0 whole blood volumes was processed per procedure. A mean white cell reduction of 64% and a mean platelet reduction of 53% were obtained per procedure on patients with leukemia and thrombocytosis, respectively. Hemoglobin levels decreased an average of 1.3 g/dl. Therapeutic cytapheresis procedures in which more than 1.5 blood volumes were processed did not result in significant additional cytoreduction.
Adult↗
In vitro study of immunologic changes in long-term cytapheresis donors.
Several in vitro measurements of immune function were examined retrospectively in a population of active long-term cytapheresis donors (group I; n = 50) and the results were compared to age- and sex-matched controls (group II; n = 50) who had donated only whole blood. In group I, significantly different mean absolute lymphocyte counts (P = .0025), total T-cells (P = .0026) and T-helper cells (P less than .0001), and helper-to-suppressor ratios (P = .0279) were present. No differences were noted between the two groups for peripheral blood mean B-cell count, T-suppressor numbers, lymphocyte responsiveness to mitogens or alloantigen, and serum immunoglobulin level. The reduced mean absolute lymphocyte count in group I was due to the reduction in T-helper cell numbers and accounted for the imbalance in the helper-to-suppressor ratio. These disturbances are currently unexplained and, while no clinical consequences have so far become evident, there is a need to continuously monitor the immunologic status of cytapheresis donors. It is also important to determine whether reversal of the defects occurs and, if so, over what time interval.
Adult↗
Cytapheresis: the first 25 years.
In vivo blood cell separator technology was originally developed in response to a perceived need for granulocytes for septic neutropenic patients. This impetus led to the development of a variety of cell separators which, paradoxically, ultimately have found their main applications in pheresis procedures other than granulocyte collection. In vivo blood cell separators are ideal for the removal of large numbers of normal or abnormal hemopoietic cells. Their early use in chronic myeloid leukemia demonstrated that leukapheresis could be used as definitive therapy for the disease. However, most hematological diseases in which the circulating malignant cells can be pheresed off have definitive and cost effective standard of care therapies, and cytapheresis is limited to specific circumstances. This paper reviews therapeutic cytapheresis and summarizes the current status of its limited specific indications.
Blood Viscosity↗
[Side-effects of continuous and discontinuous cytapheresis].
The authors evaluate the incidence of complications in 767 cytapreheses made on two types of blood cell separators. Complications, incl. technical problems before cytapheresis proper, were encountered more frequently during work with the discontinuous blood cell separators Haemonetics model 30 (27.%) than during work with the continuous automatic blood cell separator Fenwal CS 3000 (13.2%). Most frequently collapse and symptoms of hypocalcaemia were involved. Serious reactions account only for 7.6 and 4.4% of all reactions. The authors discuss the causes and possible prevention of complications during cytapheresis. With regard to the assessed results cytaprehesis by means of a separator can be considered a safe method in blood donors.
Cytapheresis↗
Cytapheresis in a patient with Sezary syndrome.
A patient with Sezary syndrome underwent cytapheresis on the IBM 2997 cell separator. Four procedures were performed over a 12-day period. A total of 8.3 x 10(10) Sezary cells were removed. The patient's skin lesions and lymphadenopathy regressed. Transient thrombocytopenia occurred, requiring platelet transfusion. Although a significant number of platelets were removed by pheresis, this was not sufficient to explain the thrombocytopenia. The patient subsequently died of causes unrelated to the cytapheresis.
Cell Separation↗