Treatment options for children and adolescents with inflammatory bowel disease: is granulomonocytapheresis an effective alternative to drug therapy?

INTRODUCTION: Patients with inflammatory bowel diseases (IBD) require life-long medications, which even if effective have the potential to cause adverse effects as additional morbidity factors. In pediatric patients, drug therapy has more serious limitations, including impaired physical and mental development. A non-drug therapeutic option is believed to be depletion of elevated and activated granulocytes and monocytes known to release inflammatory cytokines, like the CD14+CD16+ monocyte phenotype known to release tumor necrosis factor-α. Areas covered: Granulomonocyteapheresis (GMA) with an Adacolumn as a treatment option for IBD patients has been applied for the past 15 years. This article reviews the argument that GMA is a relevant and effective non-pharmacologic intervention in pediatric IBD setting. Expert commentary: GMA with an Adacolumn has shown promise in adult, pediatric, and adolescent patients with active IBD. There is evidence of post-GMA immunomodulation in terms of increased regulatory T-cell and B-cell activities. Additionally, patients who respond to GMA may attain a favorable long-term clinical course by avoiding pharmacologicals during an early phase of their active IBD. GMA has a good safety profile, especially in difficult-to-treat and pediatric settings. An additional trial is warranted to assess the efficacy of GMA in the early phase of pediatric IBD to optimize patient selection.

Efficacy of a new oxygenator-integrated fat and leukocyte removal device.

We evaluated the effectiveness of a new oxygenator-integrated device for removing lipid particles and leukocytes from shed mediastinal blood in 20 patients undergoing elective cardiac surgery under cardiopulmonary bypass. Another 20 patients undergoing cardiac surgery without the device served as controls. After filtration with the RemoveLL device, lipid particles, leukocytes, and fats were significantly reduced compared to preoperative levels. In the control group, blood fats and lipid particles at the end of cardiopulmonary bypass were significantly increased compared to preoperative levels. Leukocyte counts at the end of bypass were significantly lower in patients who had the filtration device compared to the control group. Platelets counts and hematocrit changes were not significantly different between the 2 groups.

Acute hypotension associated with leucocyte depletion filters during cell salvaged blood transfusion.

Summary Intra-operative cell salvage is used in more than 75% of NHS hospitals in the United Kingdom and is a safe and cost effective alternative to allogenic blood transfusion. We report a case of acute hypotension during reinfusion of cell salvaged blood through a leucocyte depletion filter that occurred during a caesarean section. We review the literature of hypotension associated with the use of bedside leucocyte depletion filters.

Granulocytapheresis is useful as an alternative therapy in patients with steroid-refractory or -dependent ulcerative colitis.

BACKGROUND: Recently, granulocyte and monocyte adsorption apheresis (GCAP) has been shown to be safe and effective for active ulcerative colitis (UC). We analyzed the safety and efficacy of GCAP (G-1 Adacolumn) in patients with steroid-refractory and -dependent UC. G-1 Adacolumn is filled with cellulose acetate carriers that selectively adsorb granulocytes and monocytes/macrophages. METHODS: Forty-four patients with UC were treated with GCAP. These patients received 5 apheresis sessions over 4 weeks. Twenty patients had steroid-refractory UC (group 1) and 10 had steroid-dependent UC (group 2). Fourteen patients who did not want readministration of steroids were treated with GCAP at the time of relapse, just after discontinuation of steroid therapy (group 3). RESULTS: Of 44 patients treated with GCAP, 24 (55%) obtained remission (CAI < or = 4), 9 (20%) showed a clinical response, and 11 (25%) remained unchanged. Only 2 of 10 patients (20%) with severe steroid-refractory UC (CAI > or = 12) achieved remission, whereas 7 of 10 patients (70%) with moderate steroid-refractory UC achieved remission (p < 0.05). The dose of corticosteroids was tapered in 9 of 10 (90%) patients with steroid-dependent UC after GCAP therapy. Twelve (86%) of 14 patients in group 3 showed an improvement in symptoms and could avoid re-administration of steroids after GCAP. No severe adverse effects occurred. CONCLUSIONS: The findings of this study suggest that GCAP may be a useful alternative therapy for patients with moderate steroid-refractory or -dependent UC, although cyclosporin A or colectomy is necessary in patients with severe UC. GCAP may also be useful for avoiding re-administration of steroids at the time of relapse. Randomized, controlled clinical trials are needed to confirm these findings.

Collection of peripheral blood progenitor cells with an automated leukapheresis system.

BACKGROUND: Apheresis devices designed for the collection of mature blood elements are being used for the collection of peripheral blood progenitor cells (PBPCs). The collection of PBPCs differs from that of other cells in the rarity of the target cell and in the fact that donors may undergo several days of collection. A consequence of this process may be a depletion of blood cells such as platelets from the blood. The disposable set and operating software for an apheresis device (Spectra, COBE BCT) was modified by the manufacturer to automate the collection of PBPCs and reduce the collection of unwanted blood cells. STUDY DESIGN AND METHODS: A study was initiated to compare the collection of PBPCs with the new device, the AutoPBSC (version [V]6.0 with AutoPBSC tubing set), and that with the MNC (mononuclear cell) procedure (V4.7 with white cell tubing set), for patients and healthy donors. RESULTS: Patients whose blood was processed by either theV6.0 orV4.7 procedure achieved the target dose of 5 x 10(6) CD34+ cells per kg of patient weight in similar numbers of procedures, even though the calculated collection efficiency for CD34+ cells using the automated V6.0 procedure was significantly less than that with the V4.7 procedure for both allogeneic donors and patients donating PBPCs. The collection efficiency for platelets was lower with the V6.0 procedure, and components collected in this manner contained fewer platelets. Apheresis by the V6.0 procedure required 30 to 60 more minutes per procedure than apheresis by the V4.7 procedure. Review of engraftment kinetics after transplantation did not reveal any effect of the collection procedure on recipients of either allogeneic or autologous transplants. CONCLUSION: The collection efficiencies of the V6.0 procedure for both CD34+ cells and mature blood cells are lower than those of the V4.7 procedure. The lower collection efficiency for platelets results in a smaller drop in peripheral blood platelet count after the procedure. The automated features of the V6.0 procedure may simplify PBPC collection, but this procedure requires a longer apheresis.

The effects of a neutrophil elastase inhibitor (ONO-5046.Na) and neutrophil depletion using a granulotrap (G-1) column on lung reperfusion injury in dogs.

BACKGROUND: Activated neutrophils are reported to be closely involved in ischemia-reperfusion injury after lung transplantation. We investigated the beneficial effects of a new recombinant specific neutrophil elastase inhibitor, ONO-5046.Na, and an extracorporeal-type granulotrap (G-1) column on ischemia-reperfusion lung injury, by using an in situ warm lung ischemia model in dogs. METHODS: Warm ischemia was induced for 3 hours by clamping the pulmonary arteries and veins. The left main bronchus was bisected and reanastomosed prior to reperfusion. The left lung was collapsed for 3 hours. A total of 27 adult mongrel dogs were divided into three groups: the control group (n = 9) treated with a saline vehicle; the ONO group (n = 9), in which ONO-5046.Na was continuously administrated from before induced ischemia and to ending 2 hours after reperfusion; and the G-1 group (n = 9), in which a G-1 column was applied for 90 minutes starting 30 minutes before reperfusion under passive bypass support. RESULTS: Circulating neutrophils in the G-1 group decreased significantly (p<.05) compared to preischemia, and significantly decreased compared with the other groups after reperfusion. Oxygenation was improved actually and pulmonary vascular resistance was kept lower level after the administration of ONO-5046.Na. The increase of lung weight was significantly ameliorated in both the G-1 and ONO groups. In the histopathological study, lungs from the control group demonstrated diffuse alveolar edema, neutrophil infiltration, massive alveolar exudate and hemorrhage, and thickening of the interstitium. Lungs from the G-1 group showed mild swelling of the alveolar wall and neutrophil infiltration. Lungs from the ONO group showed virtually no abnormalities. CONCLUSION: This study demonstrated that a neutrophil elastase inhibitor and neutrophil depletion prevented lung reperfusion injury. These treatments may prevent ischemia and reperfusion injury in lung transplantation.

[Activation of bradykinin formation cascade on receiving autologous blood transfusion through a white cell-reduction filter in a patient treated with an ACE inhibitor].

We have experienced a case of anaphylactoid reaction on receiving autologous blood transfusion through a WBC filter for packed red blood cell (PRBC). The patient was a 71-year-old man with a history of hypertension treated with oral antihypertensive drug; enalapril, an angiotensin converting enzyme (ACE) inhibitor, who received anesthesia for Y-graft replacement. Autologous blood was obtained after the induction of general anesthesia in the operating room. Upon starting to return the stored blood with an unintentional use of a WBC filter, arterial blood pressure (ABP) fell within the first minute of the transfusion. We obtained three blood samples; pre-filtered blood (PRE), postfiltered blood (POST) and arterial blood (CIRC) after the event, and analyzed concentrations of bradykinin (BK), high molecular weight kininogen (HMWK) and high molecular weight kininogen-light chain (HMWK-LC). BK was higher in POST than in PRE. HMWK was lower in POST than in PRE, while HMWK-LC was higher in POST than in PRE. HMWK in CIRC was lower than in PRE, and HMWK-LC was higher in CIRC than in PRE. HMWK and HMWK-LC changes after the event suggest that BK formation cascade in the patient was activated on receiving the transfusion. ACE inhibitors were reported to augment such activation. The WBC filter has the negatively charged surface on filteration material and may activate the cascade. While WBC filters can avoid transfusion related reactions, hemodynamic responses should be watched closely in patients treated with ACE inhibitors.

Cardiopulmonary bypass for adult patients: a survey of equipment and techniques.

OBJECTIVES: The techniques and equipment used for cardiopulmonary bypass for adult cardiac surgery vary among institutions and may change over time. This study sought to document the changing patterns of practice. DESIGN: Voluntary survey of meeting participants. SETTING: 13th Annual San Diego Cardiothoracic Surgery Symposium (February 1993). PARTICIPANTS: There were 331 responses from perfusionists (79.5%), cardiac surgeons (11.2%), and anesthesiologists (6.3%). The majority of these participants were from institutions where more than 1,000 cardiac operations were performed annually. MEASUREMENTS AND MAIN RESULTS: It was found that 91.5% of the respondents used membrane oxygenators currently, compared with 5% in 1982 (as reported in a previous survey). Over 80% of the institutions surveyed used some type of perioperative cell-salvaging technique. Arterial line filters were used by 92% of the respondents compared with 64% in 1982. Also, 80% of the respondents were aware of the availability of leukocyte-depleting filters. CONCLUSIONS: The probable reasons for the increased utilization of membrane oxygenators and arterial line filters include less damage to the formed elements of blood, fewer gaseous microemboli, and better control of carbon dioxide elimination and oxygenation. The authors anticipate that future surveys will document increased use of leukocyte-depleting filters because of the literature implicating neutrophils as mediators of tissue destruction in various disease processes, including myocardial reperfusion injury.

A strategy for processing of peripheral blood stem cells utilizing the small volume collection chamber and cryopreservation without a rate controller using pentastarch.

Standardization of protocols for processing peripheral blood stem cells (PBSC) will be important for multiinstitutional studies. For this reason, a strategy was developed utilizing the small volume collection chamber (SVCC) in the Fenwal CS-3000 PLUS Blood Cell Separator and cryopreservation without a rate controller in medium containing pentastarch. Use of the SVCC allows for a small extracorporeal volume, extraction of a minimal number of platelets, and a high efficiency of mononuclear cell (MNC) removal. Advantages of the pentastarch cryopreservation technique include reduction in technician time compared to controlled rate cryopreservation and use of lower concentrations in DMSO. Clinical studies using the SVCC and pentastarch technique demonstrate that these goals have been accomplished. Furthermore, patients transplanted with cells that were processed by this technique engrafted faster and were discharged sooner than patients receiving autologous bone marrow transplants.

Large volume leukapheresis to maximize peripheral blood stem cell collection.

Large volume leukapheresis, defined as the processing of greater than three volumes of blood at one sitting, can be safely and easily performed using a variety of cell separators in a range of patients. This paper describes the history, technique, outcome, complications, and proposed uses for this procedure.

Successful collection of peripheral blood stem cells from an infant with acute lymphoblastic leukemia using the Haemonetics V50.

Peripheral blood stem cells (PBSC) were collected using the Haemonetics V50 from an 8 month old infant weighing 7.8 kg suffering from acute lymphoblastic leukemia in the first complete remission. Leukapheresis was performed according to an exchange transfusion procedure by the two arm method using only a single lumen Broviac catheter. No problem occurred in the patient during this procedure except for a reduction (by half) of the initial platelet count. This method enables one to collect PBSC very safely, even from infants, in a manner that is painless for patients.

[Permselect--a new substance for leukocyte elimination]. / Permselect--ein neues Material für die Leukozytenelimination.

Permselect particles consisting of purified plant cell wall ghosts obtained from the biomass of a suspension culture of Chenopodium album L. show a very high efficiency for leukocyte binding. A package containing 1 g dry Permselect eliminates 99-100% of leukocytes from 80 ml of fresh blood, preserved whole blood, or red blood cell concentrates. At comparable conditions Permselect shows a higher efficiency of leukocyte binding than commercial filter material (cotton, cellulose acetate). The vitality parameter of filtered erythrocytes and their stability during storage were not altered. The data are discussed with respect to causality of leukocyte binding to the pectin-containing surface of the cell wall particles.

[Tumor cell separation by cell saver and membrane filter passage]. / Tumorzellseparation durch Cell-Saver und Membranfilterpassage.

Definite suspensions of malignant cells from three human tumor cells lines (bladder, prostate and renal cell carcinom) were passed through a cell saver (Althin Mediplast) and a leucozyte removal filter (PALL RC 100) under standard conditions. The examination of the solutions did not detect any malignant cells at all. If investigations with malignant cells in the blood will confirm these results, the use of intraoperative autotransfusion in urological tumor surgery would be possible.

Concurrent comparison of the Cobe Spectra and Fenwal CS3000 for the collection of peripheral blood mononuclear cells for autologous peripheral stem cell transplantation.

Hematopoietic stem cells, collected by leukapheresis from peripheral blood, can be used as an alternative to autologous bone marrow transplantation following high-dose chemotherapy as treatment of several malignancies. We compared the ability of the Cobe Spectra and the Fenwal CS3000 to collect peripheral blood mononuclear cells (MNC) for autologous peripheral blood stem cell transplantation. Ten patients experienced repeated leukapheresis (10 L blood processed per procedure) using both instruments. Procedures were alternated between the two until a total of 7 x 10(8) MNC/kg was collected. Data from 61 Spectra and 50 CS3000 collections were analyzed. The yield (mean per procedure) of nucleated cells (NC) and MNC was higher (P less than .005) with the Spectra (0.77 x 10(10) NC and 0.54 x 10(10) MNC) than with the CS3000 (0.59 x 10(10) NC and 0.40 x 10(10) MNC). However, colony forming units (CFU-GM) were not different (P greater than .05) for Spectra (0.92 x 10(4)) and Fenwal (0.65 x 10(4) collections. Platelet contamination was lower (P less than .001) with the Spectra (2.2 x 10(11)) than the CS3000 (5.0 x 10(11)). This correlated with a higher patient blood platelet count immediately following Spectra collections (117 x 10(9)/L) versus the CS3000 (86 x 10(9)/L). Using the methods described, the Spectra product contained greater yields of NC and MNC with less platelet contamination than did the CS3000.

Peripheral blood stem cell transplantation as an alternative to bone marrow transplantation: an overview.

Stem cells capable of restoring hematopoiesis following lethal bone marrow injury circulate in the blood of many animals, including humans. When collected through leukapheresis and reinfused following high-dose chemotherapy, stem cells offer a treatment option not currently open to some patients who are unable to undergo autologous bone marrow transplantation because of tumor involvement in the pelvis, prior pelvic radiation, or intolerance to general anesthesia. After stem cell infusion, hematologic and immunologic recovery are rapid in comparison to that after autologous bone marrow reinfusion; however, in some cases platelet engraftment is slower. There is some evidence that tumor contamination in the peripheral blood is much less than in the marrow. In any event, most relapses of malignant disease occur at the site of origin and represent treatment failure rather than growth of reinfused malignant cells. Prospective controlled trials are needed to evaluate stem cell in comparison to autologous bone marrow transplantation.

Peripheral blood mononuclear cell collection from patients undergoing adoptive immunotherapy or peripheral blood-derived stem cell transplantation and from healthy donors.

The demand for collection of mononuclear cells from the peripheral blood of patients for therapeutic purposes is rapidly increasing. Automated blood cell separators are usually designed for collection of blood components from healthy donors. We reviewed safety and efficiency of collection data of a new procedure for the Fenwal CS 3000 blood cell separator in 125 collections from normal donors and 101 collections from patients after IL-2 pretreatment or chemotherapy. The new procedure set red blood cell spillovers to occur at 3.5 minute intervals, using procedure 1 with the interface detector set at 1,000 and the standard granulocyte and collection chambers. Despite significant anemia and thrombocytopenia in a large number of patients no serious procedure-related side effects occurred. The lymphocyte yield was 4.74 +/- 1.6 x 10(9) per 5 liters of blood processed in normal donors and 24.2 +/- 12.0 x 10(9) per 10 liters of blood processed after IL-2 treatment. After chemotherapy the lymphocyte yield was 4.5 +/- 3.1 x 10(9) per 10 liters of blood processed; the collection efficiency was found to be significantly lower in this group. The main problem was the platelet loss of 35.6 +/- 12% of the initial count in normal donors, 40.3 +/- 14.1% after IL-2 treatment, and 42.1 +/- 18.0% after chemotherapy. The platelet loss is, however, closely related to the preapheresis platelet count; patients with thrombocytopenia lose fewer platelets than normal donors. Therefore the procedure was found to be safe for patients with a platelet count as low as 20/nl. This report provides a basis for safe, effective mononuclear cell collection from patients with very abnormal peripheral blood counts.