All concepts, explanations, trials, and studies have been re-written in plain English and may contain errors. I am not a doctor ----------------------------------------------------------- B-cells = lymphocytes that have antibody molecules on their surface, involved in immune reactions Leukocytes = white blood cells that attack infections, involved in immune reactions Lymphocytes = cells such as B-cells and T-cells Macrophages = cells like leukocytes that fight infections and act strongly in immune reactions Pheresis = same as plasmapheresis, explained in article below Platelets = disc-shaped blood cell more prone to clumping T-cells = kind of leukocyte that acts strongly in immune reactions Thrombosis = formation of a blood clot ---------------------- APHERESIS Apheresis is a process. Whole blood is removed from a person. The blood goes through a centrifuge-type machine that separates the different components of the blood. One of the separated components is then removed and the rest sent back into the patient. The components separated and removed may include : 1) Plasma : fluid part of the blood (plasmapheresis) 2) Platelets : cells that help blood clot (plateletpheresis) 3) Leukocytes : white blood cells (leukapheresis) The purpose of apheresis is to remove the part of the blood that makes a disease worse or that causes an unhealthy condition. Examples include : PLATELETPHERESIS In rare disorders, the platelet count can be very high. Removing platelets can help avoid complications like blood clots. LEUKOPHERESIS In some cases of leukemia with very high white blood cell counts, removing excess leukocytes may help prevent complications like blood clots. PLASMAPHERESIS A process in which the fluid part of the blood - called plasma - is separated from blood cells by a device called a cell separator. The separator works either by spinning the blood at high speed to separate the cells from the fluid or by passing the blood through a membrane with holes so small that only the fluid part of the blood can pass through. The cells are returned to the person, while the plasma - which contains antibodies - is discarded and replaced with other fluid. A blood 'thinner' is often given during this procedure. A plasmapheresis treatment takes several hours. It may be uncomfortable but should not be painful. The number of treatments needed depends on the condition. An average series of 'plasma exchanges' is 6 to 10 treatments over 2 to 10 weeks. A small catheter is inserted into a vein - usually in the crook of an arm - and another tube is placed in the opposite side. Blood goes to the cell separator from one tube while the separated blood cells and replacement fluids return to the patient through the other tube. The most common problem is a mild drop in blood pressure. Other adverse reactions may begin with tingling around the mouth or in the arms or legs, muscle cramps, or a metallic taste in the mouth. Such symptoms must be reported quickly because if left unchecked, they can lead to an irregular heart beat. For patients taking drugs every day, the doses need careful monitoring and may need adjustment. This is because some drugs can be removed from the blood by the procedure. PHOTOPHERESIS (Extracorporeal PhotoChemotherapy or ECP) This is used to reverse organ rejection that does not respond to drug therapy. First you swallow a chemical called 8-methoxypsoralen or 8-MOP (methoxsalen). This chemical is only active when exposed to ultraviolet A light, so it does not harm cells not exposed to such light. The 8-MOP binds to certain parts of blood cells, especially T-cells. This makes the T-cells very sensitive to ultraviolet A light. Two hours after taking the chemical, you have leukopheresis. Your blood goes through the cell separator where white blood cells are removed temporarily, while the rest of your blood returns to your circulation. The removed T-cells are subjected to ultraviolet A light, then they are also returned to your circulation. The affected T-cells - a big factor in organ rejection - usually die within 48 hours. The affected T-cells also somehow trigger a response that suppresses T-cells that did not receive the treatment. This further reverses the rejection episode. Photopheresis takes about 4 hours and is considered safe, causing few, if any, side effects. However, your eyes must be protected for a time with glasses that block ultraviolet light to prevent them from being affected by the photoactive chemical you took. For acute organ rejection, treatment is given on 2 consecutive days followed by weekly treatments for 2 weeks, followed by treatments as needed. The procedure may also be used to fight chronic Graft-Versus-Host disease, a very serious form of 'reverse' organ rejection. Photopheresis is also used to treat T-cell lymphoma (cancer). ====================================================== The information above was taken from various medical dictionaries, encyclopedias, and other online sources. It was combined and rewritten by Jon to make it easier to understand and may contain errors. For some of the main source material, see : http://www.emedicine.com/derm/topic566.htm http://www.usc.edu/hsc/info/pr/hmm/spring99/reject.html http://www.regence.com/trgmedpol/medicine/med70.html http://www.aetna.com/cpb/data/CPBA0241.html ====================================================== CLINICAL TRIAL SUMMARIES We studied the safety and effectiveness of photopheresis for PREVENTING acute rejection of transplanted hearts. 60 consecutive first-time heart recipients randomly got either standard 3-drug therapy of cyclosporine, azathioprine, and prednisone ; or these same drugs plus photopheresis. The photopheresis group got 24 treatments, given in pairs on 2 consecutive days, for 6 months after transplant. All heart biopsy samples were graded in a blinded manner at a central pathology lab. Blood from a subgroup of 34 patients (57%) was tested for CMV (cytomegalovirus) DNA. After 6 months of follow-up, the average number of acute rejection episodes per patient was 1.44 in the standard-therapy group versus 0.91 in the photopheresis group. Significantly more photopheresis patients had only one or none rejection episodes (27 of 33) than in the standard-therapy group (14 of 27). Significantly fewer photopheresis patients had 2 or more rejection episodes (6 of 33) than in the standard-therapy group (13 of 27). There was no difference in survival at 6 and 12 months after heart transplant. CMV DNA was detected less often in the photopheresis group. CONCLUSION : Adding photopheresis to triple-drug anti- rejection therapy significantly reduced risk of organ rejection without increasing risk of infection. Title: Photopheresis for the prevention of rejection in cardiac transplantation. Authors: Photopheresis Transplantation Study Group, Barr ML, Meiser BM, Eisen HJ, Roberts RF, Livi U, Dall'Amico R, Dorent R, Rogers JG, Radovancevic B, Taylor DO, Jeevanandam V, Marboe CC Source: N Engl J Med 1998 Dec 10;339(24):1744-51 PMID: 9845709 ------------------------------------------------------- Between May of 1990 and January of 1991, seven heart transplant patients averaging 42 years old, taking 3 anti-rejection drugs (cyclosporine, steroids, and azathioprine) had 9 episodes of moderate rejection that were treated with photopheresis. The episodes did not include worsened heart function and occurred an average of 114 days after transplant. Average blood level of 8-methoxypsoralen after swallowing the chemical was 129 ng/ml. Photopheresis was done twice when less than 5 x 10 to the 9th mononuclear cells got treated with the first procedure. Of 9 rejection episodes treated, 5 required one procedure and 4 required 2 procedures. Eight of 9 rejection episodes were successfully reversed, as proven by heart biopsy done 7 days after treatment. Biopsy analysis showed that cell counts of T-cells, B-cells, and macrophages were lower than before treatment ; and had been reduced enough to account for reversal of rejection. No adverse effects were seen from the photopheresis. CONCLUSION : This small, short-term study suggests that photopheresis may be effective and safe for treating moderate rejection in heart recipients with preserved heart function. This may be an alternative to intense steroid therapy for acute rejection. Title: Successful treatment of heart transplant rejection with photopheresis. Authors: Costanzo-Nordin MR, Hubbell EA, O'Sullivan EJ, Johnson MR, Mullen GM, Heroux AL, Kao WG, McManus BM, Pifarre R, Robinson JA. Source: Transplantation 1992 Apr;53(4):808-15 PMID: 1566346 ------------------------------------------------------- We studied whether photopheresis safely reverses grades 2, 3A, and 3B heart rejection without harming heart function. Sixteen heart recipients with rejection of grades 2, 3A, and 3B got either photopheresis or steroid therapy (pulse therapy). On average, 9.8 x 10 to the 9th mononuclear cells were treated per photopheresis procedure. Photopheresis reversed 8 of 9 episodes and steroids reversed 7 of 7 episodes of rejection. Average time from starting treatment to reversing rejection was 25 days in the photopheresis group and 17 days in the steroid group. Heart function remained unchanged. NO ILL EFFECTS WERE CAUSED BY PHOTOPHERESIS. CONCLUSION : These short-term results suggest that photopheresis may be as effective as steroids for treating grades 2, 3A, and 3B rejection. The lack of side effects and apparent effectiveness of photopheresis make its further study in treating heart transplant rejection attractive. Title: Photopheresis versus corticosteroids in the therapy of heart transplant rejection. Preliminary clinical report. Authors: Costanzo-Nordin MR, Hubbell EA, O'Sullivan EJ, Johnson MR, Mullen GM, Heroux AL, Kao WG, McManus BM, Pifarre R, Robinson JA. Source: Circulation 1992 Nov;86(5 Suppl):II242-50 PMID: 1424007 ------------------------------------------------------- We studied 21 bone marrow transplant recipients (10 men and 11 women) averaging 36 years old, who had cancers of the blood producing system. Six patients had acute graft-versus-host disease (GVHD) from grade 2 to grade 3, not responding to cyclosporine and prednisone. In 15 patients - 2 to 24 months after bone marrow transplant - extensive chronic GVHD involving skin (15 patients), liver (10 patients), mouth (11), eyes (6), and white blood cells (3) developed, and did not respond to drug therapy. All patients were treated with photopheresis on 2 consecutive days every 2 weeks for the first 3 months, then every 4 weeks until GVHD cleared up. Treatment was tolerated excellently without any significant side effects. After an average of 14 treatments: 1) acute GVHD resolved completely in 4 of 6 patients (67%) 2) acute GVHD partially resolved in another 2 patients 3) chronic GVHD involving the skin completely resolved in 12 of 15 (80%) patients 4) mouth ulcers resolved in all patients 5) 7 of 10 patients (70%) with liver involvement completely resolved 6) no severe infections were seen after treatments ended CONCLUSION : Our findings suggest that photopheresis is safe and effective for acute and extensive chronic graft-versus-host disease with skin and organ involvement that resists drug therapy. Title: Successful use of extracorporeal photochemotherapy in the treatment of severe acute and chronic graft-versus-host disease. Authors: Greinix HT, Volc-Platzer B, Rabitsch W, Gmeinhart B, Guevara-Pineda C, Kalhs P, Krutmann J, Honigsmann H, Ciovica M, Knobler RM. Source: Blood 1998 Nov 1;92(9):3098-104 PMID: 9787144 ------------------------------------------------------ Recent evidence suggests that photopheresis may prolong life and help 50 to 75% of people with advanced skin T-cell Lymphoma. Also, a 20 to 25% complete response rate with photopheresis has been seen at our center in patients with Sezary syndrome. These complete responses include complete disappearance of atypical cells from the skin and blood. Sensitive testing techniques also confirm the disappearance of the malignant T-cell clone from the blood of patients with complete responses. Title: Photopheresis: clinical applications and mechanism of action. Authors: Rook AH, Suchin KR, Kao DM, Yoo EK, Macey WH, DeNardo BJ, Bromely PG, Geng Y, Junkins-Hopkins JM, Lessin SR. Source: J Investig Dermatol Symp Proc 1999 Sep;4(1):85-90 PMID: 10537015