author index to abstracts

Abstracts

1Successful Treatment With Plasma Exchange in a PatientWith Stiff-Person SyndromeGrapsa E1, Papaioannou N1, Pandelias K1, Panagiotou M1,Lagouranis A1, Maticas N2

1Renal Unit Alexandra Hospital, University of Athens,2Neurological Department, Evangelismos Hospital,Athens, Greece

Objective: The association of specific autoantibodies with Stiff-person syndrome has led to TPE with both positive and negativeresults. Through this presentation we would like to present atreatment with TPE in patient with Stiff-person syndrome, resis-tant to pharmacological and immunoglobulin therapy. Method: Aforty- five year old man came to our unit from the neurologicaldepartment in order to undergo TPE suffering from Stiff-personsyndrome which is resistant to conventional therapy. His clinicalstatus was severe because he was unable to hold his body inupright position. He also mentioned insomnia due to painfulmuscle spasms. Plasma exchange was performed using the COBESpectra machine and one plasma volume was treated. Albumin5% (2/3) and colloid plasma hydroxyethyl starch (6% HES, 1/3)were used as a replacement fluids. Peripheral vein was used asvascular access. No side-effects were observed. Results: After thesecond treatment, the patient had lower muscle pain and wasable to sleep. He improved significantly after six procedures.Thus, since he had an advancing improvement, we performedtreatment once a week for one month and after that every15 days for another month and once a month for 2 months.Autoantibodies anti GAB were negative after 12 procedures. Atthat time he was stable but as soon as we terminated the treat-ment he had a relapse of symptoms. Hence, we commenced onceagain, on a monthly basis, and his clinical status is stable.Conclusion: TPE was a very useful treatment in order to alleviatethe patient’s symptoms (painful muscle spasms) and improve thequality of his life.

2Efficacy of IAPP Therapy for AQP 4-Antibody PositiveNeurological Syndrome and Antibody Removal CapacitySatoru Ohji, Shoko Isaki, Takako Iguchi, Takao Mitsui,Kyoich NomuraDepartment of Neurology, Saitama Medical Center,Saitama Medical University, Saitama, Japan

Purpose, Methods: Anti-aquaporin 4 (AQP4)-antibody positivecases may manifest in various different clinical forms, such as

typical Neuromyelitis Optica (NMO), tumefactive lesions, brain-stem lesions and so on (AQP4-antibody positive neurologicalsyndrome: AQP4-NS). We studied (1) the efficacy of immunoad-sorption plasmapheresis (IAPP) therapy for different clinicalforms of the syndrome, (2) the changes in anti-AQP4 antibody(AQP4-Ab) titers just before and after IAPP, and (3) the associa-tion between the changes in the antibody titers and the clinicalcourses in eight patients with steroid-resistance. Results: Eightpatients with AQP4-NS had a total of 23 exacerbating events: 18events in spinal cord lesions (SCL) (78.3%), 3 events in tumefac-tive lesions (TL) (13.0%), 1 event in a brain stem lesion (4.3%),and 1 event in optic neuritis (4.3%). For treatment of the 23 events,56 IAPP sessions were performed. IAPP was effective for 12 of 18SCL (66.6%) and for other forms of the disease. AQP4-Ab titerssignificantly decreased just after IAPP (P 0.015).The IAPP adsorp-tion column successfully removed AQP4-Ab. In general, thetherapy was effective in patients who had decreased in theAQP4-Ab titers after IAPP; however, the therapy was not effectivein patients with longer duration of the disease who had manyexacerbating events. Conclusion: IAPP is effective for AQP4-NS.IAPP successfully removes the AQP4-Ab and significantlydecreases the antibody titer.The therapy was generally effective inpatients who had decreases in AQP4-Ab titers.

3Thromboelastography for Monitoring Hemostasis afterTherapeutic Plasma Exchange and Membrane DifferentialFiltration Apheresis: A Prospective StudyMariano M., Malavolti R., Bevini M., *Begliomini B.,Zaldini P., De Palma MTransfusion Medicine, *Department of Surgery, AziendaUniversitaria-Ospedaliera Policlinico di Modena, Italy

BACKGROUND: Different apheresis systems are used to treatimmunological and metabolic disorders. More selective methodsthan therapeutic plasma exchanges (TPE), now available, promisemore targeted treatments and fewer complications. Here, we reportthe changes of hemostatic parameters and TEG dynamic process inTPE and Membrane Differential Filtration Apheresis (MFDA).METHODS: TPE were performed with 4% albumin, MDFAby plasma filtration through Cascadeflo EC-50 W/RheofilterER-4000. From January 2007 to October 2008, 122 patients under-went TPE (54 pts, 367 procedures) or MDFA (68 pts, 510 proce-dures). Parameters tested are below. TEG analysis was done on 20samples on citrated native blood. Statistical analysis was done bypaired and unpaired T test, Mann Whitney U test and Wilcoxon.RESULTS: media % variation after TPE and MFDA

Therapeutic Apheresis and Dialysis 13(1):A1–A20doi: 10.1111/j.1744-9987.2009.00677.x© 2009 The AuthorsJournal compilation © 2009 International Society for Apheresis

A1

PT aPTT Fibr. ATIII Pr. S Pr. C FVIII FXIII

TPE albumin +42 +25 -54 -52 -48 -45 -49 -54Cascadeflo +28 +27 -56 -17 -37 -18 -58 NdRheofilter +33 +27 -60 -19 -38 -19 -51 -64

After apheresis procedures there were no pathological changes ofTEGs, still, a different trend could be evidenced between TPE andMFDA. No bleeding complications were observed, however, a caseof recurrent superficial venous thrombosis was observed in apatient immediately afterTPE:this finding was consistent withTEGanalysis. CONCLUSION: TEG could overcome the limitation ofconventional coagulation tests and could be a useful tool in studyingthe hemostatic abnormalities after apheresis procedures.Predictingthe haemostatic alterations induced by different procedures wouldhelp to prevent patients from procedure-related complications.

4Plasma Exchange in 4 Renal Transplant Patients WithProteinuriaGrapsa E, Psimenou E, Papaioannou N, Pantelias K,Lagouranis A, and Dimopoulos MARenal Unit Alexandra Hospital, University of Athens,Athens, Greece

Objective: Therapeutic Plasma Exchange (TPE) has been used inthe management of patients with Focal Segmental Glomeruloscle-rosis (FSGS) in transplanted kidney. Our experience is presentedwith 4 such patients who developed proteinuria 1 to 12 months afterrenal transplantation. FSGS was the primary renal disease asrevealed diagnosed by renal biopsy. Method: TPE was performedusing the COBE Spectra machine and one plasma volume wastreated. Albumin 5% (2/3) and colloid plasma hydroxyethyl starch(6% HES, 1/3) were used as replacement fluids. Pre-existing arte-riovenus fistula was used as vascular access in three patients andperipheral vein in one. No side-effects were observed during theprocedures. Results: Proteinuria was decreased in all 4 patients andrenal function was stable during the treatment.After 6 procedures,one of the patients had lower than 0.5 g of proteinuria and hestopped. One year later his urine is negative for proteinuria and hisrenal function is stable. Unfortunately proteinuria was increased assoon as we boosted the TPE intervals by more than 30 days in theother 3 patients. Thus, a fortnightly program has been arranged inorder to maintain proteinuria lower than 1 g/24 h. After a year, allthe patients have stable renal function and proteinuria lower than1.5 g/24 h. Conclusion: Plasma exchange was a useful treatment forour patients in order to decrease the proteinuria and protect therenal transplant function, but additional treatments are needed inorder to maintain the results.

Table 1. Data of the FSGS transplant patients withproteinuria

Patients First Second Third Fourth

Age(years-old)

55 40 31 58

Sex Male Male Male FemaleProteinuria

Pre TPE7.5 gr (12 mo.

after Tx)1.6 gr (6 mo.

after Tx)3.8 gr (1 mo.

after Tx)7 gr (6 mo.

after Tx)Proteinuria

Post TPE1 gr (After

10 TPEs)0.2 gr (After



6 TPEs)Relapse (+) (-) (+) (+)On periodic

TPEYes No Yes Yes

5Transition of the Peripheral Regulatory T-cell During theAdsorptive Granulocyte/Monocyte Apheresis for ActiveRefractory Ulcerative Colitis PatientsKoji Kamikozuru, Ken Fukunaga, Takayuki MatsumotoDepartment of Internal Medicine, Division of LowerGastroenterology, Hyogo College of Medicine, Hyogo,Japan

INTRODUCTION: An inadequate CD4+CD25High+ regulatoryT-cell (Treg) function has been accepted to have a direct relation-ship to the activity of ulcerative colitis (UC). Granulocyte/monocyte apheresis (GMA) has been accepted as a non-pharmacological therapy in Japan for active UC. AIMS &METHODS: We have aimed to evaluate transition of the periph-eral Treg during/ after remission induction therapy with GMA.Twenty-two active steroid refractory UC patients, whom couldachieve clinical remission after 10 weekly GMA, were enrolled.Blood specimens were obtained before and after each GMAsession. Moreover, six out from 22 subjects were asked to with-draw their blood at 35 weeks after finishing GMA. 12 of volun-teers were asked to donate their peripheral blood as control(HC). Samples were immediately stained with anti-CD4/CD25antibodies for FACS. RESULTS: Mean of %Treg before eachGMA was lower than that of HC (P < 0.05). A significant increasein %Treg was associated with 1 hour of GMA session (P < 0.05).This Treg up-regulation has dropped during session intervals, andit decreased as initial level by the next GMA. The %Treg wasincreased as same as HC when they have been in remission and ithas maintained at 35 weeks after. CONCLUSIONS: %Treg hasbeen proven to indicate an immune-disturbance in acute UC.Obtained Treg up-regulation might be a key to understand thetherapeutic mechanism of GMA. And, intensive performance ofGMA, e.g. 2 or 3 times a week, could achieve stronger clinicalefficiency by shorten interval between GMA sessions.

6Immunoadsorption Through Ig-Therasorb Columns in theTreatment of Hyperimmunized Patients Undergoing HeartTransplantationGiancarlo Isacchi1, 2, Stefano Ceccarelli2,Giovanna Del Principe2, Attilio Landolfo2

1Department of Biopathology, ImmunohematologySection, Tor Vergata University, 2Department of PediatricOncohematology and Transfusion Medicine, BambinoGesù Hospital, Rome, Italy

The PRA (panel reactive antibody) uses complement-dependentcytotoxicity techniques in order to reveal the presence of anti-HLAantibodies. Recently, a more sensitive technique has been intro-duced based on flow-cytometry as an alternative approach in orderto reveal the appearance of anti-HLA class I and class II antibodies.In heart transplantation the presence of these antibodies has beenrelated with reject episodes and with post-transplant death. Apositive PRA (>10–15%) in the recipients, determines a positivecross-matches that reduces or prevents the possibility of assigningthe heart.The immunoadsorption after antibody depletion throughIg-Therasorb columns, combined with or without pharmacologicaltherapy, can modify the antibody profile of these patients so theycan undergo a transplant with a lower risk.The goal of this study hasbeen to lead such patients to transplant with a meaningful reductionof the PRA and monitoring the successive outcome.Five candidates

AbstractsA2

© 2009 The AuthorsJournal compilation © 2009 International Society for ApheresisTher Apher Dial, Vol. 13, No. 1, 2009

to heart transplant with a PRA�20% for HLA class I and IIantibodies have been treated consecutively. The number of proce-dures for single patient is related to the value of the PRA. Theimmunoadsorption is not reported in literature with the indicationswe propose.The number of patients with congenital cardiac pathol-ogy that arrive hyperimmunized to the transplant is growing andthere still is no solution. Because the intent is to make patients witha PRA > 20% transplantable and to control the rejection in theshort post-transplant period, immunoadsorption may become animportant resource in the future of organ transplantation.

7Albumin Dialysis as Predictive Criteria for the Outcome inPatients With Acute Liver Failure?G. Novelli1, M. Rossi1, V. Morabito1, F. Ruberto2,S. Novelli3, R. Haiberger2, P.B. Berloco1

1Dipartimento “Paride Stefanini” Chirurgia Generale eTrapianti d’Organo, 2Dipartimento di ScienzeAnestesiologiche Medicina Critica e Terapie del Dolore,3Dipartimento di Ingegneria Clinica, La Sapienza, Roma,Italy

BACKGROUND: The aim of our study is directed towards theassessment of these resources in our possession that could facili-tate a decision to transplant or not. For this reason, we examinedwhether the Molecular Adsorbent Recycling System (MARS) canbe seen as a predictor of survival in patients with Acute LiverFailure. METHODS: In Intensive Care Unite (ICU) we treated 44patients with Fulminant Hepatitis (FH). Continuous MARS treat-ment was carried out on all patients. During treatment, the con-centration of albumin and albumin bound-toxins changes both inthe circuit and in the patient from hour to hour. We found idealconcentrations for every patient supported by a study among ourclinical data and the mathematical model. Detoxification is directlycorrelated to albumin concentration in patient. The higher theconcentration, the more toxins are removed. RESULTS: Of the 44patients, thirty one of which survived, 18 went to the transplantwhile 14 have continued extracorporeal methods for a maximumperiod of 17 days indicating a positive resolution of the clinicalcondition. When we obtain an improvement of GCS (>10), lactatelevels (<3 mmol/L), intracranial pressure (<15 mmHg) and achange in hemodynamic instability from hyperkinetic to normalkinetic condition between 30 and 50 hours with the treatmentMARS, we decide to continue extracorporeal treatment. Twelvepatients have died, including 3 before transplant for multiorganfailure, while nine died after transplantation. CONCLUSION: Theresults urge us to continue in this search by adjusting the numberof patients to be treated. Given favorable results (?), we have todoubt if the protocols to define a Fulminant Hepatitis are totallysatisfactory or some FH are not such!

8Successful Allograft Rescue With Immunotherapy in Anti-body Mediated Cardiac Transplant RejectionHofmann, Jan C.1,2; Weisshaar, Dana M.3; Pham, Michael4;Kiprov, Dobri D.1,2

1Apheresis Care Group, and 2Division of Immunotherapy,California Pacific Medical Center, San Francisco; 3KaiserPermanente Heart Transplant Program, NorthernCalifornia Kaiser Permanente, Santa Clara; 4AdvancedHeart Failure and Cardiac Transplant Program, VA PaloAlto Health Care System, Palo Alto, CA, USA

Introduction: Antibody-mediated rejection (AMR) in cardiactransplant patients is primarily mediated by donor-specific antibod-ies (DSAs) and is associated with reduced long-term graft andrecipient survival. Methods: We reviewed the medical records of15 heart transplant patients (pts) referred for immunotherapy,between September,2002 and October,2008,to treatAMR.Medianage of pts was 55 years (19–68 years old). Pts presented with symp-toms of CHF, diastolic and/or systolic dysfunction, and decreasedEF. 13 pts (87%) had endomyocardial biopsy results demonstratingAMR and/or evidence of circulating DSAs at the time of rejection.All pts were DSA and T-cell crossmatch negative at time of trans-plant. At time of rejection, 10 pts (67%) had circulating DSAs(including A23, B7, B53, DR13, DR53, DQ7, and DQ8). Treatment:All pts received plasma exchange (PE). 10 pts (67%) receivedpost-PE intravenous immunoglobulin (IVIg). 11 pts received con-current intravenous corticosteroids. 4 pts received other adjunctivetreatment (antithymocyte globulin, rituximab, cyclophosphamide,lymphoid irradiation). Results: 15 pts underwent PE every otherday or 3 X/week (4–6 PE treatments/course). 8 pts (53%) hadsignificant clinical improvement and 5 pts (33%) had slight-to-moderate improvement in allograft function. Of these 13 pts, 10 pts(77%) had normalization of systolic/diastolic function or substan-tial improvement in EF. 8 of 11 pts (73%) in whom DSAs weremeasured had significant reduction of class I MHC levels. 4 pts(27%) have recurrent AMR requiring chronic PE. Conclusion: PEand IVIg can be effective in providing successful graft rescue forheart transplant patients with antibody-mediated rejection.

9Autologous Platelet Rich Plasma as a Biological Adhesivein Lamellar KeratoplastyF. Luengo1,, J.I. Ferro2, S. Gatto2, S. Arias2, J.O. Croxatto3

and J.E. Gallo1

1Department of Ophthalmology, 2Medical TransfusionalService, Hospital Universitario Austral and Facultad deCiencias Biomedicas, Pilar, Buenos Aires, 3OcularPathology, Fundacion Oftalmologica Argentina “JorgeMalbran”, Buenos Aires, Argentina

Purpose: To demonstrate the usefulness of autologous platelet richplasma (PRP) as a biological adhesive in lamellar keratoplasty(LK). Methods: An autologous six millimeters lamellar graft wasperformed in 12 albino rabbits. Autologous PRP was applied onthe stromal surface and the corneal botton was replaced. Topicaltobramicin and dexametasone were postoperatively used. Rabbitswere euthanized for histological evaluation at 48 h, 1, 4, and12 weeks after surgery. Results: Clinically, all the rabbits showedsuccessful graft attachment and clear cornea at 12 weeks. Histo-pathologic examination showed mild inflammation in the initialstages and a well adhered lamellar graft with mild keratocyteactivity at 12 weeks. Conclusions: Autologous platelet rich plasmamay be a useful tool in lamellar keratoplasty and flap adherenceafter LASIK.

10Membrane Plasmapheresis in Treatment of FulminantHepatic Failure Due to Overdose With Anabolic Steroids:A Case ReportKovac J, Knap B, Marn-Pernat A, Buturovic-Ponikvar J,Bren AF and Ponikvar RDepartment of Nephrology, University Medical Centre,Ljubljana, Slovenia

Abstracts A3

© 2009 The AuthorsJournal compilation © 2009 International Society for Apheresis Ther Apher Dial, Vol. 13, No. 1, 2009

Objectives: A 33-year old professional football player suffered anacute hepatic failure as a result of the excessive use of anabolicsteroids. In the treatment of this fulminant hepatic failure, mem-brane plasmapheresis (MPF) was performed. During the first tendays of hospitalization, hepatic failure was progressive. During thefollowing three days, three MPF procedures were performed.Methods: Table 1 presents data about the MPF procedures.

Body mass 82 kgHematocrit 0.34Estimated 1 plasma volume 3.5 LInfusion fluid

Hemofiltration fluid 3 L (bicarbonate conc. 32 mmol/L)20 % human albumin 0.5 L

Anticoagulation Standard heparinVascular access 2 peripheral veinsBlood flow 70–110 ml/minDuration of MPF 2 h 30′—2 h 45′Complications 0

Results: Table 2 presents laboratory data before and after threeMPF procedures.

Laboratorytest

Before1st MPF

After1st MPF

Before2nd MPF

After2nd MPF

Before3rd MPF

After3rd MPF

Bilirubin total(mmol/L)

1060 715 906 605 818 510

Bilirubin direct(mmol/L)

678 546 639 470 588 420

Ammonium(mmol/L)

40 23 38 11 24

Total proteins(g/L)

56 44

Albumin(g/L)

38 36

Fibrinogen(g/L)

2.8 2.0

INR 1.1 1.2 1.4

Conclusion: Before MPF was performed, hepatic failure was pro-gressing fulminantly.With the above-mentioned treatment, hepaticfailure was reversed. During the following course of treatment thepatient regained normal hepatic function and later also success-fully continued his professional career.

112007 International Apheresis RegistryPaul S. Malchesky1, Anna P. Koo2, Christine Skibinski2,Angela T. Hadsell1, Lisa A. Rybicki2

1The International Center for Artificial Organs andTransplantation, Painesville and 2Cleveland Clinic,Cleveland, OH, USA

The developments in apheresis technologies and techniques andtheir clinical applications worldwide are technologically, socio-logically, and economically motivated. As in past apheresissurveys, the statistics have highlighted both the differences bygeographic region in clinical practice and in the types of tech-nologies utilized. While a national view of apheresis is veryimportant, an international view is likely more representativeoverall of this therapeutic modality than national results that arehighly dependent on the local economics and the available tech-nologies. These regional differences have provided a basis for sci-entific and clinical assessment of these apheresis technologiesand their clinical outcomes and have impacted the marketing and

business developments of new technologies worldwide. The Inter-national Apheresis Registry for 2007 reports data from 19 centersin 15 countries on over 1,700 patients. The data, collected fromthe volunteering participating centers via an internet-basedwebsite, includes patient demographics, medical history, diseasestreated, treatment specifics (type, methodology, access type, anti-coagulants and drugs used), side-effects, clinical responses andpayment providers. The results of this 2007 International Apher-esis Registry will be discussed in light of the reported resultsfrom the national registries. The results will also illustrate differ-ences in treatment modalities as well as new developments intherapeutic apheresis technologies and their application world-wide. These results can then be further assessed to determineemerging trends as well as the efficacy and clinical outcomes ofthese apheresis therapies.

12Diabetes Mellitus and Autologous Bone Marrow DerivedProgenitor Cell Transplant (A-BMDPCT): CooperativeInternational Study, Uruguay-MéxicoNovoa JE, Medina A, Gordillo F, Pérez Chavez F,Soto Valdez M, Pérez Chavez A, Ortega A, Cazares R,Estela R, Olivet C, Caride RHospital Policial, Montevideo.Uruguay, UniversidadAutónoma de Nuevo León, México, Clínica Real,Montevideo, Hospital de San Carlos, Maldonado, MSP,Uruguay

Introduction: Diabetes mellitus (DM) accounts for more than 250million people around the world. Aims: To improve the quality oflife of diabetic patients obtaining its metabolic control and even-tual side effects of the Autologous Bone Marrow Derived Progeni-tor Cell Transplant (A-BMDPCT). Methods and Patients: FromJuly 2004 to March 2008, 165 diabetic patients were evaluated forthis study. 85 men and 80 women with a median age of 66 years old(range 8–92) were studied. 65 patients were from Uruguay (Hos-pital Policial, MSP) and 100 from México (UANL). 39 patients hadType 1 DM, and 126 had Type 2 DM. All signed informed consentforms. We excluded patients with cancer in the last five years,IV degree diabetic retinopathy, active smoking, morbid obesityand life expectancy less than 6 months. Cell concentration wasobtained by gradient of density. Mobilization with filgrastim wasemployed; 5 ug/kg/weight in two doses 48 h before transplantation.Local anesthesia was used in 161/165 for harvest and transplanta-tion in the gastrocnemius muscle. In four patients intravenousanesthesia with propofol was employed. Unmanipulated bonemarrow progenitor cells were implanted applying the Conzi’seffect in one of the lower limbs in two ml aliquots. Mean volume ofharvest was 2.8 ml/kg/body weight.The mean number of implantedmononuclear cells was 2.4 ¥ 109/kg body weight. 24 h after trans-plant, the patients received nadroparine 3800 IU anti-Xa s/c, clo-pidogrel 75 mg p/o daily and pentoxiphilin 400 mg p/o daily, during30 days. Each patient was evaluated regularly for glycemia, A1chemoglobin, C peptide, and BMI (body mass index).The mortalityrelated to the A-BMDPCT was 0%. The only complication washematoma in the transplanted leg (4.5%). Results: 85% of type 2and 44% of type 1 diabetic patients obtained metabolic control,discontinuing the oral or insulin treatment for more than 180 days.Conclusion: Autologous bone marrow derived progenitor celltransplant applying the Conzi’s effect, can be performed safely andappears to be a beneficial complementary therapy for human dia-betes mellitus.

AbstractsA4


13Leukocytapheresis for Severe Active Ulcerative ColitisPatient Concomitant With Cytomegalovirus InfectionKoji Nogami1, Ken Fukunaga1, Yoko Yokoyama1,Koji Kamikozuru1, Kyouichi Kato1, Katuyuki Tozawa1,Shiro Nakamura1, Hiroto Miwa2, Takayuki Matsumoto1

Department of Internal Medicine, 1Division of LowerGastroenterology, 2Division of Upper Gastroenterology,Hyogo College of Medicine, Hyogo, Japan

Background: CMV infection is an exacerbation factor inulcerative colitis (UC) patient. Approximately 30% of UC withsteroid-refractory acute flare has been reported to complicateCMV colitis. We have investigated clinical effectiveness of leuko-cytapheresis (LA), a non-steroidal therapy, for such CMVinfected UC patient with severe flare. Aims & Method: 47 severeUC were admitted to us from February to October, 2008. And, 18(38.3%) patients had CMV infection on admission. Their CMVinfection was diagnosed by either CMV DNA-PCR (colonicbiopsy) or C7-HRP (serology). 11 of 18 had received LA. Wehave compared the remission ratio between LA and non-LAgroups. Moreover in LA group, we have evaluated their clinicaland endoscopic backgrounds. Result: 9/11 (81%) achieved clinicalremission after 10 weekly LA sessions, whereas that of non-LAgroup was only 2/7 (28%). In the LA group, only clinical activityindex, established by Lichtiger, was significantly different betweenLA responder and non-responder groups in their clinical back-ground(P < 0.05). And in LA non-responders, their colorectalmucosa has been revealed to have deep and multiple ulcers,which has been accepted as specific endoscopic findings of CMVinfection. Conclusion: The CMV colitis could be appeared inpatients under immune-deficient condition. Since current medica-tions, such as steroid and immunosuppressants, for active UChave aimed to suppress patients’ immune-reaction, there are con-flicting interests of the treatments for these two diseases. Effec-tiveness and safety of LA have been proven to be appropriate foractive UC patient concomitant CMV infection.

14Red Cell Exchange Employing Phenotipically MatchedDeglycerolized Red Blood Cells to Treat Acute SickleCell CrisisDel Fante C1, Isernia PM1, Villa MA2, Viarengo GL1,Perotti C1, Salvaneschi L1

1Immunohaematology and Transfusion Service, Center forTransplant Immunology, Fondazione IRCCS Policlinico S.Matteo, Pavia, 2Milano Rare Groups Blood Bank,Fondazione IRCCS Policlinico Ospedale MaggiorePoliclinico, Milano, Italy

Objectives: Red cell exchange (RCE) is a safe and rapid pro-cedure to reduce circulating HbS in order to treat or preventacute complications of sickle cell (SS) disease. Ethnic differencebetween donor population and red blood cell (RBC) recipients iscritical to heighten the possibility of alloimmunization againstforeign antigens. RBC transfusion respecting the patient’s pheno-type is mandatory even in presence of RBC’s rare phenotype. Wedescribe our experience by RCE in treating a pts with SS crisisusing deglycerolized RBC obtained from Milano Rare BloodBank, respecting the rare pts’ phenotype: 0, ccDee,K-k+,Fy(a-b-).Methods: An 18 yo African male with SS crisis (acute pain, mor-phine resistant and inability to walk), was first treated in urgency

with 4 deglycerolized RBC using Fresenius COM.TEC device.A second (after 88 days) and a third (after 200 days) RCE wereprogrammed employing 3 fresh identical and 3 deglycerolizedRBC units/procedure to prevent SS crisis. Pts and procedure char-acteristics are shown in Table 1. Summary of Results: Post proce-dure pts’ laboratory tests are shown in Table 1. Pts’ symptomsresolved immediately after RCE. There was no evidence of intraor post-procedure hemolysis. No immediate or late RCE relatedside effects were recorded. At 9 months, pts’ follow up docu-mented a stabilization of the clinical conditions and laboratorytests. Conclusions: Our experience demonstrates feasibility andsafety of RCE using deglycerolized RBC units permitting theideal transfusion management thus abolishing the risk of alloim-munization.

PreRCE pts dataRCE

characteristicsPostRCEpts data

n. TBV(ml)

HbS/HbC(%)

Tot bili(mg/dL)

K+mEq/L

DRBC/meanHct%

FRBC/meanHct%

TotRBC(ml)

HbS(%)

K+(mEq/L)

1 4602 50.6/41.7 4.9 3.5 4/37 0 1160 38 3.42 4602 46.9/38.9 5.58 4 3/36.5 3/70 1500 24 3.83 4602 48.4/35.7 6.3 3.8 3/39 3/59 1466 31 3.9

Table 1. Patient’s characteristics before procedure 1, 2 and 3 andcharacteristics of the RBC units exchanged.TBV = pts’ total bloodvolume; DRBC = deglycerolized RBC; FRBC = fresh RBC; TotRBC = Total RBC volume exchanged. Pts’ post procedure values:HbS and HbC are automatically calculated by the FreseniusCOMTEC software basing on the pre-procedure values.

15World Apheresis Association Registry: 2003–2007 DataStegmayr B4, Ptak J3, Wikström B5, Berlin G6,Axelsson CG7, Griskevicius A1, Centoni P2,Liumbruno G2, Molfettini P2, Audzijoniene J1,Mokvist K5, Nilsson Sojka B4, Knutson F12, Norda R 12,Prophet H10, Ramlow W10, Blaha M8, Witt V9,Evergren M13, Tomaz J11, Newman E14,Lalic K15, Stojkovski L16.Vilnius, Lithuania1, Livorno, Italy2, Frydek-Mistek3,Hradec Kralove8, Czech Republic, Umea4, Uppsala5,12,Linkoping6, Orebro7, Huddinge13, Sweden, Rostock,Germany10, Vienna, Austria9, Coimbra, Portugal11,Liverpool, Australia14, Belgrade, Serbia15, Skopje,Macedonia 16

Objectives: 75 centers from many countries have applied for alogin code to the WAA apheresis registry. 18 centers from 10countries have been actively entering data at the internet sitefrom 2003 until November 2008. We report on knowledge basedon data from the registry so far. Methods: This is a web-basedregistry. A link is available from the WAA homepage (www.worldapheresis.org). So far data from 2,495 patients (16067 pro-cedures) have been included. A median of 6 treatments havebeen performed (range1–140). Mean age 51 y (range 1–94 years;45% women). Seven percent of the patients were �21 years and4% were �16 years. Results: The purpose of the apheresis pro-cedure was therapeutic in 67% and retrieval of blood compo-nents in 33%. Main indications: neurological and hematologicaldiseases, lipid apheresis and stem cell collection (autologous, andsome allogeneic). Blood access: peripheral vessels (71%), centraldialysis catheter through jugular (6.5%) or subclavian veins

Abstracts A5


http://www.worldapheresis.org


(6.7%), femoral vein (8%) and AV fistula (4%). ACD was usedfor anticoagulation in 73% of the procedures. Albumin wasmainly used as replacement fluid. Adverse events (AE) were reg-istered in 5.6% of the procedures. AE was graded as mild (1.9%),moderate (2.7%) or severe (0.5%). No death occurred due totreatment. The procedures were interrupted in 2.6%. Most fre-quent AEs were blood access problems (29%), tingling aroundthe mouth (20%), hypotension (18%), and urticaria (9%). Therewere significant differences between the centers regarding mildand moderate AEs. Data indicate that centers using continuousinfusion of calcium had fewer AEs. Conclusion: There were alimited number of severe AEs. Centers use various standard pro-cedures for apheresis. By learning from the experience of othersthe treatment quality will improve further. In the near future, anupdate of the registry will enable more extensive evaluation ofthe data.

16World Apheresis Registry: New VersionStegmayr B4, Larsson T4, Ptak J3, Wikström B5, Berlin G6,Axelsson CG7, Griskevicius A1, Centoni P2,Liumbruno G2, Molfettini P2, Audzijoniene J1,Mokvist K5, Nilsson Sojka B4, Knutson F12, Norda R 12,Prophet H10, Ramlow W10, Blaha M8, Witt V9,Evergren M13, Tomaz J11 Newman, E14, Lalic K15,Stojkovski L16.Vilnius, Lithuania1, Livorno, Italy2, Frydek-Mistek3,Hradec Kralove8,Czech Republic, Umea4, Uppsala5,12,Linkoping6, Orebro7, Huddinge13, Sweden, Rostock,Germany10, Vienna, Austria9, Coimbra, Portugal11,Liverpool, Australia14, Belgrade, Serbia15, Skopje,Macedonia 16

Objectives:The WAA apheresis registry was established in 2003. Ithas grown and 18 centers from 10 countries have been activelyentering data at the internet site until now. Data from more than16000 procedures have been entered. However, registries seldomallow evaluation of therapeutic interventions. Many comparativestudies will not be initiated by industry for economic reasons. Wewill report on the new version of the apheresis registry that enablesthe input of outcome data. By inserting data regarding varioustreatment options for the same diagnosis the effectiveness ofvarious treatment models can be compared even for rare diseases.Methods: This is a web-based registry. A link is available from theWAA homepage (www.worldapheresis.org). The new version issimilar to the previous one but also allows entry of data of treat-ment mode and outcome variables for several of the diseases. : Inaddition, centers not using apheresis at all for a specific diseasecould enter their treatment data in order to make it possible tocompare apheresis treatment to other treatment modalities.Results: The registry contains data for various diagnoses and aph-eresis procedures as well as adverse events. In addition, the newversion contains data on clinical outcome adjusted for the indi-vidual treatment diagnosis. Thus, for Wegener’s granulomatosisinformation will be entered on serum creatinine, clearance, anti-body titers, dialysis therapy, ventilator therapy, and mode of treat-ment for example. Conclusion: The new version of the WAAregistry will allow evaluation of interventions even at subtle levels.Although data will not be randomized a similar to centre-randomization concept could be expected especially, if centers notusing apheresis will enter their treatment data. Thus, we invite allcenters to participate.

17Apheresis for Rheumatic DiseaseKen YamajiDepartment of Internal Medicine and Rheumatology,Juntendo University School of Medicine, Tokyo, Japan

The main stream of treatment for rheumatic disease is pharmaco-therapy. Corticosteroids and DMARDs, immunosuppressiveagents and biologics are the gold standard of the treatment.However, some cases showing resistance to these treatments exist,and the potential for side effects exists in all of these pharmaco-therapies. Furthermore, there are cases in which pharmacotherapycannot be effectively used due to organ derangement. Apheresis istotally different from pharmacotherapy as a concept, and it is atreatment to control disease activity by removing the factors whichcontribute to the pathogenicity. The Synchronized therapy of aph-eresis and pharmacotherapy is the treatment that may result in amore beneficial effect of treatment. This review introduces theexperiences as an overall approach to better, safer management forrheumatic diseases.

18Therapeutic Angiogenesis in Arterial Limb Ischemia byAutologous Bone Marrow Progenitor Cell Transplantation(A-BMPCT)-CELLTHER Program: International Coop-erative Study Uruguay-MéxicoNovoa JE, Medina A, Gordillo F, Pérez Chávez F,Soto Valdez M, Pérez Chávez A, Estela R, Olivet C,Cazarez R, Ortega A, Caride RHospital Policial, Montevideo, Uruguay, UniversidadAutónoma de Nuevo León, Monterrey, México, Hospitalde San Carlos, Maldonado, MSP, Uruguay

Background: Therapeutic angiogenesis has recently been devel-oped as a new method of treatment for several ischemic diseases;both experimentally and clinically there are preliminary data sug-gesting that implantation of bone marrow-mononuclear cells intoischemic limbs increases collateral vessels formation. Aims:To evaluate viability of the therapeutic angiogenesis using bonemarrow progenitors mobilized by G-CSF (granulocyte colonystimulating factor) and safety of the procedure. Methods: 70patients developing critical arterial limb ischemia (candidates foramputation) were included in this study (38 men and 32 women).Median age was 63 years old. BMMCs were mobilized by filgrastim5 ug/kg weight daily (5 days) with bone marrow harvest at the 6th

day. Local anesthesia was employed in most patients (63/70) with2% lidocaine for harvest and cell implantation. Unmanipulatedbone marrow progenitor cells were obtained by density gradientand implanted in the affected limb in two ml aliquots into thegastrocnemius muscle. The mean number of transplanted mono-nuclear cells was 2.1 ¥ 109/kg. After the procedure, all the patientsreceived fraxiparine 3800–5600 IU anti X-a subcutaneously, aspirin81 mg/daily, and pentoxifiline 400 mg/daily for 60 to 90 days.A control population of 68 vascular patients affected by criticalarterial limb ischemia was considered. They did not receive theangiogenesis treatment, only the same antithrombotic scheduledescribed. Results: The procedure mortality rate was 0%. No sec-ondary side effects were registered related to G-CSF. Moreover, in70 patients with a median follow up of 40 months, 63 showed animprovement of all the parameters evaluated, mainly rest pain,peak walking time and ulcer trophic lesions.Three patients sufferedamputation of the affected extremity because obstruction of an oldbypass (4.3%).In the control population,amputation was necessary

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in all the patients before 18 months of outcome. The statisticaldifferences between the two groups were highly significant (chisquare and log rank test) P < 0.05. Conclusions: Our data suggestthat autologous bone marrow derived progenitor cell transplanta-tion can be performed safely and appears to be a beneficial therapyfor selected patients with severe peripheral arterial disease.

19Preparation of Platelet-Rich Plasma as a Tissue Adhesivefor Experimental Transplantation in RabbitsFederico Luengo Gimeno1, Silvia Gatto2, José Ferro2,Juan Oscar Croxatto3, Juan Eduardo Gallo1

1Department of Ophthalmology, 2Transfusional Service,Hospital Universitario Austral, Universidad Austral, Pilar,Argentina

Purpose: Platelet-rich plasma (PRP) is an autologous substancewith adhesive properties. We aimed at developing and testing theefficacy of a method for PRP preparation in rabbits. Materials andmethods: An in vitro study was carried out to obtain PRP fromforty rabbits and to analyze the number of platelets and type ofsubstance needed to trigger platelet activation. To induce plateletactivation, 5%, 10%, 25% and 50% CaCl solutions were used.Then, an in vivo study was performed in twelve rabbits to test PRPadhesiveness in lamellar corneal graft.A control group made up ofsix rabbits underwent corneal transplantation without using PRP.Results: 5% CaCl was the most effective concentration in activat-ing PRP, with a mean time of 19 minutes. An attached corneal flapwas seen 3 months after surgery. A detached corneal button wasseen in all controls. Conclusion: Our method was able to producerabbit-derived PRP with suitable properties for soft tissue adhe-sion. These results could be useful for researchers of the growingfields of tissue repair and experimental transplantation.

20Autologous Bone Marrow Derived Progenitor Cell Trans-plant (A-BMDPCT) in Parkinson’s Disease: CooperativeInternational Study, México-UruguayNovoa JE, Medina M, Pérez Chávez F, Soto Valdez M,Rangel Guerra R, Pérez Chávez A. Plachin V, Ortega A,Cazares R & Caride RUniversidad Autónoma de Nuevo León, Monterrey,México. Hospital Policial, Montevideo, Uruguay. ClinicaReal Terapia Celular. Montevideo, Uruguay. CellTherInternational Program for Cell Therapy

Background:The most common cause of Parkinsonism is idiopathicParkinson’s disease, a neurodegenerative disease, first described byan English physician Dr. James Parkinson in 1817. Current therapycan not avoid progression. Objectives: Control of symptoms andsigns of the disease and quality of life, evaluate other additionaltherapeutic effects, evaluate the presence of side effects related tothe autologous bone marrow derived progenitor cell transplanta-tion in this group of patients. Methods: From July 2007 to March2008,20 patients were evaluated to be included on this protocol withneurological diagnosis of idiopathic or primary Parkinson’s disease(IPD).13 men and 7 women with a median age 70 years old (range53–87). For the initial evaluation score and follow up the UnifiedParkinson Disease Research System (UPDRS) scale was em-ployed. The control group was the same cohort of patients in thesix months before A-BMDPCT. Local anesthesia was employedin 9 patients with 2% xilocaine for harvest and transplantation inthe gastrocnemius muscle. General anesthesia with propofol was

received for the other 11 patients. Bone marrow cell concentrationwas obtained by density gradient. Mobilization with filgrastim wasemployed, 5 ug/kg of body weight daily (two doses) before trans-plantation (48 hours). Unmanipulated autologous bone marrowderived progenitor cells were implanted in one of the lower limbs in2 ml aliquots.The mean number of bone marrow mononuclear cellswas 2.2 ¥ 109/kg body weight. Results: The procedure mortalityrate was 0%. The only complication of this treatment was localhematoma in the transplanted leg (5%). 70% of patients showed apositive answer to treatment with disappearance of IPD symptoms.This clinical response was maintained for six months or more in allthis patients. Conclusions: autologous bone marrow derived pro-genitor cell transplant, by the “Conzi-Fortunato effect” can beperformed safely and appears to be a beneficial complementarytherapy for patients with idiopathic Parkinson’s disease.

21Treatment of Hyperlipidemic Acute Pancreatitis withPlasma Exchange—Retrospective Slovenian Cohort of48 patientsGubenšek J, Marn Pernat A, Kovac J,Buturovic Ponikvar J, Benedik M, Varl J and Ponikvar RDepartment of Nephrology, University Medical CenterLjubljana, Ljubljana, Slovenia

Objective: Although the optimal therapy of acute hyperlipidemicpancreatitis (HLP) is not entirely clear, plasma exchange (PE)rapidly lowers triglyceride levels. We report our experiences withPE in the setting of HLP. Methods: 48 patients with HLP weretreated with PE between 1992–2008. 92% were male, their agewas 45 � 8 years. During each PE 1–2 plasma volumes wereexchanged. We used bicarbonate-based electrolyte replacementsolution with 30 g/l albumin. Circuit was anticoagulated withheparin in 84% of cases. PE was repeated to maintain triglyceridelevels below 10 mmol/L. Serum cholesterol and triglycerides weremeasured before and after PE. Survival and length of hospital staywere recorded retrospectively. Results: Total of 77 PE were done.Volume exchanged was 4870 � 1300 ml over 3.5 � 2 h duration.During the first PE triglycerides were lowered from 57.8 � 40.4to 10.9 � 10.9 mmol/Land total cholesterol was lowered from19.3 � 7.9 to 5.8 � 4.3 mmol/L. In 8 procedures (10%) plasmafilterwas replaced and in 2 (3%) the filter clotted.There was one case ofsevere gastrointestinal bleeding after PE. For the 2003–2008 cohort(35 patients) hospital mortality rate was 5/35 (14%) and overallhospital stay was 5–142 days, median of 19 days. Conclusions: Inacute hyperlipidemic pancreatitis 1–2 PE effectively reduce serumtriglyceride levels below 10 mmol/L. There is a low rate ofprocedure-related complications.The mortality rate of 14% is con-siderable.

22CARL: Extracorporeal Elimination of Liposomes Used inCancer Treatment: First Clinical ResultsPütz, Gerhard, Eckes, Jürgen, Schmah, Oliver, Wieland,Heinrich, Winkler, KarlUniversity of Freiburg Medical Center, Dept. ClinicalChemistry, Freiburg, Germany

BACKGROUND: Using highly toxic drugs like chemotherapeuticagents, therapeutic success is often limited by severe adverse effects.For example, the use of doxorubicin is restricted by severe cardiactoxicity. To lower the acute and chronic cardiac toxicity of doxoru-bicin, long circulating liposomes (e.g. DOXIL/CAELYX) can be

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used as drug delivery systems. Thereby the toxic profile of theencapsulated doxorubicin is shifted, but detoxification of drugs notreaching the tumor still remains an obstacle. Nanoscale particlebased drug delivery systems like liposomes accumulate to someextent in tumor tissues,but still only a very small portion of the givendose reaches the target tissue.Accumulation within the tumor takesseveral hours, and when accumulation is completed, still a mainportion of the administered chemotherapeutic agent is circulatingin the plasma. Finding a way to eliminate this portion will lower thepatients burden of toxic agent and may diminish severe adverseeffects during chemotherapy.DOXIL/CAELYX,the most commonliposomal chemotherapeutic agent, can be eliminated by doublemembrane plasmapheresis treatment. Based on these findings, apilot study was initiated to evaluate the safety and efficacy of CARLin vivo. The first preliminary results of this study will be reportedhere. METHODS: For the pilot study Doxil/Caelyx is used asliposomal chemotherapeutic agent and double membrane plasma-pheresis is used for extracorporeal elimination of the liposomes.Elimination efficacy and safety profile will be evaluated with 12patients.As secondary parameter side effects and quality of life willbe evaluated. RESULTS: After the first treatments (n = 4), thesepreliminary results were found: extracorporeal elimination ofCaelyx by apheresis is very efficient.Approx. 70% (�1%) of circu-lating doxorubicin is eliminated by filtration of 1 plasma volume.When apheresis was started, ~ 75% (�2%) of the total given dosewas circulating in the plasma, after apheresis was finished, ~21%(�5%) were left circulating. Thus ~54% (�3%) of the total dosewere eliminated. No leakage of doxorubicin was detected duringapheresis treatment.Apheresis was well tolerated.The first patientsdid not show any skin toxicities (hand feet syndrome/mucositis),which are frequent dose limiting side effects in these patients.CONCLUSION: Extracorporeal elimination of liposomal doxoru-bicin may be as safe and efficient as apheresis of lipoproteins. Basedon the first clinical outcome, CARL is very promising to reduce thesevere side effects seen during chemotherapy. Since these resultsare preliminary, we are looking forward to get more reliable resultson a larger number of treatments.

23Cardiodepressant IgG3 Autoantibody Elimination by Im-munoadsorption in Patients With Dilated CardiomyopathyAkiyasu Baba, Tsutomu YoshikawaDepartment of Cardiology, Kitasato Institute Hospitaland Keio University School of Medicine, Tokyo, Japan

Objectives: By blinded measure of cardiodepressant IgG3 autoan-tibody (AAb) before and after immunoadsorption (IA), we com-pared cardiac improvement between success and failure of thisAAb perfect elimination. Methods: By IMMUSORBA-TR (AsahiKasei Kuraray Medical CO, Tokyo, Japan), the selective IgG3absorber, we removed cardiodepressant AAb from the body of 17DCM patients (NYHA class III or IV, left ventricular ejectionfraction (LVEF) less than 30%). We measured all LVEF by quan-titative 99 m-Tc gated SPECT. All patients had anti beta1-adrenergic and/or M2-muscarinic AAb before IA. However, targetcardio-depressant AAb was measured before and after IA inblinded fashion, and cardiac function and prognosis between com-plete and imperfect treatment groups was compared. Results:The following clinical parameters were improved just after IA(P < 0.01); 6 minutes walking test (314 � 124 vs. 360 � 94 m), CTR(61 � 6 vs. 58 � 6 %), BNP (827 � 699 vs. 523 � 529 pg/ml).However, LVEF in 17 patients had no change just after IA. Incomplete treatment group (n = 8), we can eliminate perfectlycardio-depressant AAb by IA, which was also blinded till therapy

effect determined 3 months after IA. LVEF increased significantlyin complete than in the imperfect group (20 � 8 to 29 � 9 vs.18 � 10 to17 � 7 %, P < 0.01) 3 months after IA. Moreover,cardiac insufficiency events were more frequent in imperfect thanin the complete group. Conclusions: This apheresis treatmentrequires complete elimination of cardiodepressant AAb.

24Extracorporeal Photopheresis as Salvage Therapy inChronic Lung RejectionPerotti C1, Del Fante C1, Meloni F2, Lastoria C2,Viarengo GL1, Salvaneschi L1

1Immunohaematology and Transfusion Service, Center forTransplant Immunology, Fondazione IRCCS Policlinico S.Matteo, 2Clinic of Respiratory Diseases, University ofPavia and Fondazione IRCCS Policlinico S. Matteo,Pavia, Italy

Objectives: Infusion of UVA-irradiated autologous leukocytescollected by apheresis and extracorporeally incubated with8-methoxypsoralen (ECP), has demonstrated its safety and effi-cacy in treatment of heart and, more recently, lung, liver, andkidney rejection. Although ECP mechanism of action is not com-pletely clarified it has been shown to induce expansion ofT-regulatory and/or tolerogenic dendritic cells. Long term LungTransplant (LTx) survival is hampered by a high rate of chronicrejection (bronchiolitis obliterans syndrome: BOS) notwithstand-ing multidrug immunosuppression (IS). We recently started anECP salvage program for LTx pts not responsive to standard IS.Methods: 14 pts (10 M and 4 F; median age: 50 (�14) years) withgraft dysfunction (BOS grade 1: 6, BOS grade 2: 5, and BOSgrade3: 3) were enrolled. Pts characteristics are shown in table 1.ECP was performed according to “French method”. ECP was performed bimonthly in the first 2 months and monthly thereafter.Progressive ECP tapering and discontinuation depended on graftfunction (according to ISHLT guidelines). Summary of results:Individual FEV1 trends pre and post ECP initiation are shown inFigure 1. Overall a stabilization of graft function was observed in10/14 pts (4/6, 4/5, and 2/3 with BOS 1, 2 and 3 respectively). NoECP-related adverse events were observed. Conclusions: A sixmonth ECP treatment was effective in stabilizing graft function in

% FEV1/FEV1best

0

20

40

60

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100

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Pts 1

Pts 2

Pts 3

Pts 4

Pts 5

Pts 6

Pts 7

Pts 8

Pts 9

Pts 10

Pts 11

Pts 12

Pts 13

Pts 14

Figure 1. Time course of FEV1 (percentage of the best post-transplant FEV1 value) during ECP treatment.

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71% of BOS patients. Further studies are needed to confirm ECPapproach as salvage therapy in LTx pts with lung dysfunction.

25Membrane Plasma Exchange for the Treatment of Throm-botic Thrombocytopenic PurpuraMarn Pernat A, Buturovic-Ponikvar J, Knap B, Kovac J,Benedik M, Varl J, Kersnic B, Gubenšek J, Žugic R,Ponikvar RDepartment of Nephrology, University Medical CenterLjubljana, Ljubljana, Slovenia

Objectives: The aim of our report is to present 11-year experiencewith therapeutic membrane plasma exchange therapy (MPE) inthe treatment of idiopathic thrombotic thrombocytopenic purpurasyndrome (TTP). Methods: In 56 patients MPE was initiatedimmediately and performed once or twice daily until the plateletcount has normalized. During each MPE procedure 1 to 1.5 plasmavolumes (3606 � 991 ml) were replaced with fresh frozen plasmaor cryo-poor plasma in non-responders. Anticoagulation withheparin was used in 24 patients and 4% trisodium citrate in32 patients. Summary of Results: In 37 females and 19 males(44 � 21 years), 1066 MPE procedures were performed. Theaverage duration of treatment was 23 � 17 days. The averagenumber of MPE was 19 � 17 per patient. Renal impairment wasdetected in 36% of patients. At start of MPE the average plateletcount was 31 � 30 ¥ 109/L and reached 199 � 95 ¥ 109/L there-after. Fifty-one of 56 (91%) patients demonstrated excellentresponse to MPE, of whom 47 patients (84%) attained completeremission with platelet count of more than 100 ¥ 109/L. Fourpatients died soon after initiation of MPE, when only 1 to 3 pro-cedures were performed. During follow up period, 6 patients withcomplete remission had subsequent 1 to 5 relapses once a year and3 of them underwent additional splenectomy. Conclusions: Our11-year experience with primary TTP supports the MPE with freshfrozen plasma as a mandatory up-to-date therapy. Close monitor-ing during all 1066 procedures showed no serious side-effects.

26Guillain-Barré Syndrome Treated by Membrane PlasmaExchange and/or ImmunoadsorptionMarn-Pernat A, Buturovic-Ponikvar J, Žugic R, PremruV, Ponikvar RDepartment of Nephrology, University Medical CenterLjubljana, Ljubljana, Slovenia

Objectives:The aim of our study was to evaluate success of plasmaimmunoadsorbtion (IA) and plasma membrane exchange (MPE)therapies in patients with severe Guillain-Barré syndrome (GBS)in our center between 1998 and 2008. Methods: Nineteen GBSpatients, aged from 14 to 76 years, were retrospectively studied.Allpatients were tetraparetic and 16 needed mechanical ventilation.Ten patients were previously unsuccessfully treated with intra-venous immunoglobulin. IA therapy was performed in 9 patients,MPE with human albumin in 5 patients and 5 patients receivedboth type of apheresis modalities. Decision regarding the durationof apheresis therapy was based on clinical improvement, such asartificial ventilation requirement and walking recovery. Summaryof Results: Thirteen male and six female patients underwent 161IA and 119 MPE procedures. Mean plasma volume processed was10171 � 1968 ml per IA, and 4300 � 1304 ml per MPE treatment,respectively. In severe GBS 4 to 30 IA and 5 to 31 MPE sessions

were needed. There were no significant differences in the averagenumber of IA and MPE per patient (11.5 � 7.0 vs11.9 � 11.2,p = NS). Among 16 patients on mechanical ventilation, 11 recov-ered from disability completely and in one mild muscle weaknesspersisted. One patient suffered from ischemic stroke, two patientsdied after weaning from mechanical ventilator. One death wasbelieved to be procedure unrelated, the other patient died fromsepsis. Four patients were lost during follow up. Conclusions: Highnumber of IA as well as MPE treatments can be safely and effec-tively applied in severe GBS patients. Our patients often neededmore than currently arbitrary accepted 4 apheresis sessions beforegood clinical recovery was achieved.

27LDL Apheresis in Two Children With HomozygousFamilial HypercholesterolemiaPremru V, Marn-Pernat A, Kovac J, Knap B, Žugic R,Buturovic-Ponikvar J, Ponikvar RDepartment of Nephrology, University Medical CenterLjubljana, Ljubljana, Slovenia

Familial hypercholesterolemia is an inherited functional impair-ment or absence of hepatocyte LDL receptors. Homozygous formis rare, affecting 1–2/milion inhabitants. Accelerated atherosclero-sis causes early death. LDL apheresis is an option being superior toplasmapheresis. Lipoprotein particles are selectively cleared byadsorption. We analyzed efficacy and safety of long-term LDLapheresis in two patients:A 13-year girl begun with LDL apheresiswith initial LDL-cholesterol 17.8 mmol/L. Post-procedural LDL-cholesterol is below 2 mmol/L while pre-procedural concentra-tions reach 6–7 mmol/L. In more than 17 years of treatment therewere no side effects besides some initial bradykinin reactions.There are no clinical or morphological signs of progressive athero-sclerosis. Patient is fully rehabilitated. Second patient began as a4-year boy with LDL-cholesterol 21.6 mmol/L, first treated byplasmapheresis and switched to LDL apheresis after 5 years. Pre-procedural LDL-cholesterol was 9.1 mmol/Land post-proceduraldecreased to 1.2 mmol/L. Initial problems with vascular accesswere overcome by AV fistula creation.After 11 years he received aliver transplant. Conclusion: In patients with homozygous familialhypercholesterolemia, pharmacologic treatment is insufficient. Ifliver transplantation can not be performed, then LDL apheresis isefficient and safe long-term treatment alternative.

28Therapeutic Angiogenesis by Peripheral Blood Stem Cellin Patients with Peripheral Arterial DiseaseMotoki Yonekawa, Takashi Horie, Ichiro Tsuda,Jun-ichi Iida, Hiromi Sakata,Hidenori Furui, Tohru Tamaki, Kazutaka Kukita,Jun-ichi Meguro, Akio KawamuraDepartment of Surgery, Sapporo Hokuyu Hospital,Sapporo, Japan

Introduction: Therapeutic angiogenesis using bone marrow celltransplantation has been reported and is useful in patients witharteriosclerosis obliterans (ASO). We applied the same procedureusing peripheral blood stem cell collection (PBSCC) in patientswith PAD. Materials: One hundred and thirty-five patients withPAD were included in this study. One hundred and twenty-fivepatients had PAD in lower limbs, and 11 had in upper limbs.Ninety-three of them had chronic renal failure and were treated

Abstracts A9


with hemodialysis. Methods: Patients were administered 5 mg/kg/day of granulocyte-colony stimulating factor (G-CSF) for 4 dayssubcutaneously. PBSCC was done on day 4. In each patient, 8.4 L ofperipheral blood was treated with an apheresis machine (CS-3000or Spectra) and 3.4 ¥ 107 of CD34 cells were harvested with mono-nuclear cells. The number of red blood cells and platelets did notchange. We did not purify the CD34 cells using magnetic beadsmethod.The CD34 enriched fluid (56.8 ml) was injected into 60–190points of limb muscle on the same day. Results: Forty-one patientsshowed marked improvements in their limb hemodynamics. Thedisappearance of limb ulcers continued for 5 years. The symptomsof other 39 patients did not improve, but their limbs were avoidedthe amputations. On the other hand, 55 patients were treated withsurgical amputations, because their ulcers deteriorated and wereinfected. Conclusion: The CD34 enriched fluid was obtained byG-CSF injection and PBSCC. Intramuscular injection treatmentsimproved the limb hemodynamics in early stage of PAD,but did notsuccess the avoidance of amputations in end stage.

29Biospecific Sorbent for Removal of Antierythrocytic Anti-bodies From Human PlasmaPokrovsky SN, Klesareva EA, Korchagina EA*,Afanasieva OI, Levashov PA, Adamova IYu**,Bovin NV*Cardiology Research Center, *Institute of BioorganicChemistry, **POCARD Ltd., Moscow, Russia

The removal of specific antibodies from the plasma of patients ispromising method for solving many of transplantology problems.One of the causative factors in the graft rejection, selected by theantigens of histocompatibility, is incompatibility on the bloodgroups according ABO system. Extracorporeal immunoabsorptionfor removal of anti-A and anti-B antibodies from patients plasmatransplantation is considered as a major protective procedure inorder to avoid hyperacute and acute vascular rejections. The syn-thetic oligosaccharides A (Atri) and B (Btri), was covalently linkedto agarose beads by different methods with and without a polymerspacer. Three types of prepared sorbents were applied to thesamples of human plasma of O blood group with high titer ofspecific antibodies. The removal of specific antibodies by Atri-sorbents and/or Btri-sorbents varied from 70 to 90% of corre-sponding specific immunoglobulin’s (IgG and IgM) from humanplasma. All samples of sorbents were of high stability during ster-ilization, regeneration and multiple used. The developed sorbentbind only specific antibodies without cross-binding with otherplasma components. The specificity and efficacy of designed sor-bents was the same as active ingredient of commercially availablecolumns “Glycorex” (Glycorex Transplantation AB).We hope thatthe sorbents with synthetic oligosaccharide can be very perspectivefor the development of the new columns generation for specifictherapeutic apheresis techniques. This work was executed withfinancial support of the Ministry of Science and Education ofRussian Federation (grant No 02.512.11.2100)

30New Peptides Based Affinity Sorbents for IgG ApheresisLevashov PA, Afanasieva OI, Afanasieva MI,Bespalova Zh D, Azmuko AA, Palkeeva ME,Adamova IYu*, Pokrovsky SNCardiology Research Center, Moscow; *POCARD Ltd.,Moscow, Russia

A new selective sorbents for the human IgG adsorption havebeen developed. The aim of this study was the creation of newmaterials based on principally new ligands—short peptidesenable to bind human IgG. The development of these sorbentswill allow us to overcome the main disadvantages of bacterial(protein A) and mammalian (antibodies against human IgG) pro-teins immobilized in most currently available sorbents for Ig aph-eresis procedures. The molecular design of new ligands has beenintended for binding of a constant part of immunoglobulin Gmolecules. The new sorbents were prepared by covalent immobi-lization of original aromatic di/tri-peptides on agarose matrix. Itwas shown that the new sorbents effectively adsorb human IgG.These peptides can become effective ligands for creation of thenew generations of sorbents for the therapeutic Ig apheresis. Weexpect that the advantages of the new proposed sorbents, namelystability and synthesis simplicity of proposed peptides, open wideprospects for the developing of the new chromatographic mate-rials for medicine and biotechnology. This work was executedwith financial support of the Ministry of Science and Education ofRussian Federation (grant No 02.512.11.2100)

31New Sorbent With Chimeric Synthetic Antigen for the Spe-cific Removal of Autoantibodies Against b1-adrenoreceptorFrom DCM PatientsAfanasieva OI, Berestetskaya YuV, Levashov PA,Afanasieva MI, Bespalova JD, Sidorova MV,Adamova IYu*, Pokrovsky SNCardiology Research Center, *POCARD Ltd., Moscow,Russia

Dilated Cardiomyopathy (DCM) is a serious type of heart failureand autoimmune disease and one of the reasons of heart trans-plantation. Preliminary data prove that removal of IgG by thera-peutic apheresis from the patients with DCM lead to significantimprovement of patient’s status. Autoantibodies from the sera ofthe DCM patients are the antibodies against their own proteinslike b1-adrenoreceptor, myosin, sarcolemmal laminin, M2 muscar-inic receptor, ribosomes, mitochondrial proteins and many others.Autoantibodies to b1-adrenoreceptor are the most investigatedautoantibodies found in the sera of the some DCM patients.That’swhy for the successful treatment of DCM it is necessary to havespecific sorbent for autoantibodies removal and the test for theirdetermination. Synthetic antigen consisting of two peptides fromdifferent loops of the b1-adrenoreceptor molecule, connecting byextra and also inter loop disulfide bridges was synthesized as wellas immunosorbent on its basis. The affinity chromatography of thepatient plasma showed a statistically significant difference(p < 0,005) in IgG removal between DCM patients and healthydonors, using sorbent with such chimeric molecule as ligand. Alsowe compare the binding capacity of sorbent with synthetic antigenand sorbent with mixing of sorbets with peptides from loops 1 and2 of b1-adrenoreceptors (analog of the active ingredient of thecolumns for therapeutic apheresis “Coraffin”—“Fresenius MedicalCare”). The efficacy of specific IgG removal by designed sorbentwith synthetic antigen was significantly higher than the other cur-rently available sorbents. This work was executed with financialsupport of the Ministry of Science and Education of Russian Fed-eration (grant No 02.512.11.2100)

AbstractsA10


32Specific Lp(a) Apheresis. Whom, When and How?Pokrovsky SN, Afanasieva OI, Ezov MV, Adamova IYu,*Kipor SG*, Konovalov GA**Cardiology Research Centre, **MedSi Clinic, *POCARDLtd., Moscow, Russia

Lipoprotein (a) [Lp(a)] has to be conducted as independent riskfactor for the development of atherosclerosis in the coronary,carotid, and peripheral arteries. In some cases severe coronaryheart disease (CHD) developed especially in the meddle agemale with normal TC and LDL-C due to elevated Lp(a) level(>30 mg/dl). Currently there are practically no effective drugsavailable which can sufficiently lower Lp(a). Because of thatrecently we have developed specific sorbent which contain sheeppolyclonal antibodies against human Lp(a) covalently linked toagarose beads, such columns have been called “Lp(a) Lipopak”and used for the treatment of severe CHD patients by specificLp(a) apheresis procedure which differ from routine LDL apher-esis. We demonstrate that “Lp(a) Lipopak” columns can be lowerLp(a) level in the patient’s blood up to 80% with high specificity.Improvements of the patients including the regression in thesome segments of coronary arteries have been shown in differenthospitals in Russia, Germany and UK. It is important to under-stand that specific Lp(a) apheresis and routine LDL apheresis aredifferent approaches. How responsible physicians can prescribeLDL apheresis for the patients with normal LDL? Whom?—Tothe severe CHD patients with solo elevated Lp(a) and normalLDL Cholesterol without and/or with lipid lowering drug therapy.When?—as early as possible. How?—by “Lp(a) Lipopak”columns only, because all other available systems for lipids aph-eresis (Liposorber, DALI, HELP, LDL TheraSorb, LDL Lipopak,Lipocollect, Cascade filtration) was originally designed for theextracorporeal LDL Elimination. Conclusion: Specific Lp(a) aph-eresis is the innovative, unique, safe and effective treatment forsevere CHD patients with elevated Lp(a) and normal LDL level.Multicenter trial, according unified protocol, to create additionalevidence for proposed therapy is requested.

33Long-term Management With Leukocytapheresis foran Elderly Onset Rheumatoid Arthritis Patient:A Case ReportYukihiro Matsuda1,2, Yoshinari Takasaki2

1Division of Rheumatology, Chiba Social InsuranceHospital, 2Department of Internal Medicine &Rheumatology, Juntendo School of Medicine, Chiba,Japan,

The present case is an 86 year old male. He had histories of pul-monary tuberculosis(47 y.o.)and bladder cancer(79 y.o.). He wasdiagnosed as having a RA(stageII class2) and prescribed predniso-lone 5 mg and salazosulfapyridine 1000 mg daily in September2003. Subsequently, 150 mg of mizoribine was added daily,however, the effects were limited. Based upon his age and histories,methotrexate and biologic agents were not applicable. Therefore,Leukocytapheresis was initiated from May 30th, 2004. CellesorbaCS-100(Asahi kasei medical) was used as the leukocyte removalfilter and nafamostat mesilate was used as the anticoagulant.Plasauto LC was used as the monitor. 3 L of blood was treated oneach session and 5 sessions were performed weekly. Side effectsassociated with Leukocytapheresis were not noticed. Symp-toms were improved significantly[Visual analogue scale of

pain(VAS) (8.2to3.3 cm), swollen joint count(SJC)(10to2),tender joint count(TJC)(7to0), modified Health AssessmentQuestionnaire(mHAQ)(13to6)]. Since deteriorations of his symp-toms were observed 4 months later, more 5 sessions were per-formed weekly. As the results, symptoms and laboratory data weresignificantly improved. [VAS(6.9to3.3), SJC(10to4), TJC(9to1),mHAQ(11to6)] [C-reactive protein(CRP)5.91 to 1.49 mg/dl eryth-rocyte sedimentation rate(ESR)120 to 87 mm/hr.] His conditionwas well maintained until August, 2006 when the third course of 5sessions was performed. His symptoms and the data were gradu-ally improved and CRP became negative 6 month after the thirdcourse. [VAS(2.8to1.8), SJC(6to2), TJC(6to1), mHAQ(6to2)][CRP 3.21 to 0.02, ESR 95 to 54.] His conditions have been wellmaintained over 2 years after the third course.Leukocytapheresis was considered to be useful for elder RApatients.

34Efficacy of Immunoadsorption Plasmapheresis in Myasthe-nia Gravis and Change in Serum Cytokines and ReactiveOxygen MetabolitesAkihiro Kubota, Takako Iguchi, Satoru Ouji,Wataru Hara, Shinya Narukawa, and Kyoichi NomuraDepartment of Neurolgy, Saitama Medical Center,Saitama Medical University

Objectives: Immunoadsorption plasmapheresis (IAPP) was per-formed to treat myasthenia gravis (MG) in the exacerbationphase, and the changes in serum cytokines, reactive oxygenmetabolites (d-ROM), and biological antioxidant power beforeand after therapy were investigated. Subjects and Methods: Thetherapeutic effect of IAPP was investigated in 43 patients withMG. The plasma separator OP-05W, TR350 column were used forIAPP, and the mean volume of plasma treated per session was2,000 ml. Ten types of serum cytokines, d-ROM, and biologicalantioxidant power were measured before and after therapy.Results: The efficacy of IAPP was evaluated on the basis of neu-rological symptoms at 1 and 2 weeks after therapy. A substantialimprovement was found in 80% and 56% of patients at 1 and2 weeks after therapy, respectively. Analysis of serum cytokinesbefore and after IAPP showed a decrease in IFN-g and anincrease in IL-10. A significant decrease in d-ROM was foundafter therapy (P < 0.001), with no significant change in biologicalantioxidant power. Conclusions: IAPP decreased IFN-g, aninflammatory cytokine, and d-ROM, with a positive correlationbetween IFN-g and d-ROM.

35Leukocytapheresis as a Therapeutic Option for IntractableInflammatory Bowel DiseaseTakayuki MatsumotoDepartment of Internal Medicine, Division of Lower G-IDisease, Hyogo College of Medicine, Hyogo, Japan

As Inflammatory Bowel Disease (IBD) including Ulcerativecolitis (UC) and Crohn’s disease (CD) is a chronic recurrentdisease with unknown etiology. In the guidelines,5-aminosalycilates are standard treatment for mild disease andhigh dose cortico-steroids are often used in moderate-to-severedisease. However, IBD patients who are resistant to or depen-dent of cortico-steroids are likely to develop problems in qualityof life due to adverse effects of drugs. For such IBD patients,

Abstracts A11


immune-modulators such as cyclosporine A (CyA) is usually con-sidered before surgery, however, it also has potential adverseeffects. Therefore, it is essential to develop other therapeuticoption with safety. Extracorporeal leukocyte removal therapy(cytapheresis) is one of the adjunctive therapies for IBD patientrefractory to steroids, through suppression of impaired immuneresponse by removing circulating activated leukocytes, especiallygranulocytes and lymphocytes, and it is approved at the year of2000 in Japan. Current data in Japan shows that cytapheresis iseffective and safe for steroid resistant IBD in moderate-to severecondition except for fulminant cases. Cytapheresis is more effec-tive for steroid naïve or resistant case without longterm continu-ous treatment with steroid. It is also recommended to use in anearly stage of the disease. Although there are a few randomizedcontrolled trials (RCT) with conflicting results, clinical experi-ence in Japan for about 10 years so far suggests that cytapheresishas favorable efficacy as a non-pharmacological therapy, espe-cially in safety characteristic comparing with other conventionalmedications for severe UC. It is also approved for CD this yearin Japan.

36Therapeutic Erythrocytapheresis In Patients HBsAg+ AndHCV+ With Hemochromatosis1Di Domenico Gilda G., 2Mottola Maria M.,1Leonardi Gaspare Michele G.M., 1Nocera Cosimo C.,2Zuccarelli Bruno B.1Immunohematology Service Hospital S. G. Bosco, ASL,2Immunohematology Service Hospital V. Monaldi, Naples,Italy

Objectives. Hereditary Hemochromatosis (HH) is a genetic dis-order characterized by an increased intestinal absorption of ironand following accumulation in different organs. Classical therapyincludes phlebotomy and/or pharmacological therapy. In selectedcases, therapeutic erythrocytapheresis (EA) becomes the maintreatment. In the present work we describe two cases of theerythrocytapheresis medical practice in two patients, respectively,HbsAg + and HCV+, affected by hereditary hemochromatosis.Methods. Erythrocytapheresis (EA) treatment was performedthrough cellular separator Fresenius COM.TEC, using theprogram of red cells depletion. Results The first treated patientwas a 38-year-old man affected by a chronic hepatitis HBsAg +and Hereditary Hemochromatosis (HH). He demonstrated aserum ferritin value of 1404 ng/mL and the molecular biologyanalysis of the HFE gene showed the presence of homozygotemutation C282Y. Owing to the liver disease and of the high levelsof ferritin, it was started a cycle of therapeutic erythrocytapher-esis. The patient was submitted to following therapeutic program:a session EA/week for 3 weeks and one a month for the follow-ing 4 months. The values of haemoglobin (Hb), hematocrit (Ht)and ferritin at the start of the therapy were respectively: 14,8 g/dl,45% and 1500 ng/mL. After the first 3 sessions we observed areduction of the 68% of the serum ferritin value (451 ng/mL),while Ht and Hb were respectively of 40% and of 13,9 g/dl. Thecontrols performed at the end of the therapeutic treatmentshowed a 97% serum ferritin decrease (50 ng/mL), reaching, insuch way, the desired target. The second treated patient was a60-year-old man affected by a chronic hepatitis correlated HCV.He showed a serum ferritin value of 1200 ng/mL, Hb 13,2 g/dland Ht 40%. The high serum ferritin levels induced us to hypoth-esize the presence of Hereditary Hemochromatosis. Molecularbiology analysis of the gene HFE has shown the presence of

homozygote mutation C282Y. The patient was therefore candi-date, according to our protocols, to erythrocytapheresis treat-ment. He was submitted to the following therapeutic program: asession EA/ week for 3 weeks and one a month for the following2 months. After the first 2 sessions, the ferritin was decreased of70% (350 ng/mL), while Ht and Hb were respectively of 41%and of 11,6 g/dl. The patient was submitted therefore to theadministrations of Erythropoietin (EPO) 40.000 UI/ss, perform-ing a vial every 7 days. The patient is still in treatment and thelast controls of laboratory has shown a serum ferritin value of195 ng/mL, while the levels of Hb (13,3 g/dl) and Ht (42%) havere-entered in the normal range. Conclusions These data show agreat effectiveness of the program of iron-depletion through EAin patients HbsAg+ and HCV +, with HH. On the other hand, thecoupled treatment with EPO and EA has shown is to able toquickly reduce the serum ferritin values, and to prevent theanaemic status EA—induced

37Feasibility and Tolerance of Erythrocytapheresis forPatients With Sickle Cell DiseaseM. Atassi-Dumont1

1Centre Clinique d’Hémobiothérapie, HôpitalPitié-Salpétrière.Assistance-Publique-Hôpitaux de Paris,Paris, France

Red blood cell (RBC) exchange transfusion has been developedfor the treatment of acute complications of sickle cell disease(SCD), and transfusion programs are indicated to prevent com-plications (stroke . . . ). Erythrocytapheresis (EA) permits auto-mated and standardised exchange transfusions. This study aims toassess, feasibility and tolerance of EA for ambulatory patients.Materials and methods: Patients were divided in two groups:Group 1, single exchange transfusion, Group 2, chronic transfu-sion program. Results: 51patients (pts) referred for EA, 25 inGroup 1 and 26 in Group 2. 456 EA were performed: Group 1 39EA, 33 by peripheral venous accesses—6 by central venous cath-eter. Group 2, 417 EA, 186 by peripheral venous accesses- 68 bycentral venous catheter, and 163 by arteriovenous fistula. Imme-diate tolerance was good, with 8 side effects for 456 EA (1,7%),among them 6/8 were reversible, enabling to complete EA.Delayed side effects: RBC Alloimmunization for 1 patient (antikpa) (5/51 patients were alloimmunized at entry of study). Noiron overload occurred for the 26 pts in Group 2, with an averagefollow up of 29 months (3 to 60 months), and a mean number of106 RBC units transfused per patient (30 to 576 RBC units).Conclusion: EA was easy to perform and very well tolerated.Transfusion programs with EA permitted to avoid iron overloadin chronically transfused patients.

38Activated Blood Cells’ Removal as a Potential to PredictClinical Efficiency of Leukocytapahresis for IBD PatientsFukunaga, Ken,1) Hida, Nobuyuki,1) Ohda, Yoshio,1)

Yoshida Koji,1) Yokoyama, Yoko,1)

Kamikozuru, Koji,1) Kato, Kyouichi,1) Nogami, Koji,1)

Tozawa, Katsuyuki,1) Nakamura, Shiro,1) Miwa, Hiroto,2)

Matsumoto, Takayuki1)

Division of Lower1) and Upper2) Gastroenterology,Hyogo College of Medicine, Nishinomiya, Japan

AbstractsA12


OBJECTIVES: In Japan, Leukocytapheresis (LCP) has beenaccepted as an adjunct for ulcerative colitis (UC). It could beaccepted that a direct removal of patients’ blood cells during LCPplay a pivotal role in its mechanism. Hence, we have focused on theimmune-characteristics of removal cells in order to evaluate LCP.We have summarized our previous data regarding these points.METHODS: Peripheral whole blood has obtained from active UCpatients submitted for weekly LCP. The specimens were thenstained with CD4/CD25 for lymphocytes and/or CD63/CD62-Pimmediately prior to FACS analysis. RESULTS: LCP has beenaccepted to perform with either filtration (LCA) or adsorption(GMA) in Japan. GMA was associated with a significant increasein the level of immune-regulatory T-cells (Treg), CD4+CD25High

phenotype, measured at the end of GMA (P < 0.05, n = 24). InLCA, a significant decrease in the level of activated-platelets,CD63+CD62-P+ phenotype, measured at the end of LCA (P < 0.05,n = 7). Interestingly, these significances were not proven in a groupof LCP non-responders. DISCUSSION: We found that Tregexpression in UC was increased after GMA; thus, UC relapsemight reflect the loss of the Treg activity in the circulation. Theincrease in the expression of circulating Treg following a GMAsession is novel and potentially should contribute to the clinicalefficacy of GMA. In LCA, we proved that the therapeuticresponses to LCA were reflected in modulations of populationand/or platelet functions. These modulations of such activatedblood cell induced after LCP may be an early marker for predict-ing its response.

39A Case of Mixed Cryoglobulinemia HCV Associated WithAtypical Therapeutic Response To Plasma Exchange1Mottola Maria M., 2Di Domenico Gilda G.,1Masini Edoardo E., 1Meluccio Edgardo E.,2Nocera Cosimo C.,1Zuccarelli Bruno B.1Immunohematology Service Hospital V. Monaldi,2Immunohematology Service Hospital S.G. Bosco, ASLNaples. Naples, Italy

Objectives. The Mixed Cryoglobulinemia (MC) is a pathologycharacterized by the presence of serum Immunoglobulins (Ig)which are able to precipitate at a cold temperature (<37°C). Tra-ditionally, it is classified in three types: I, II, III.Types II and III arenamed MC, composed of monoclonal or polyclonal IgM respec-tively, having rheumatoid factor activity directed towards antigenicdetermining of the other Igs. Numerous studies have shown, inapproximately 80% of the cases, a correlation between HCV infec-tion and CM appearance. The therapy of the CM is performedby immunosuppressive treatments (Interferon in HCV positivepatients) and plasma exchange (PE). In the present study, wereport a case of a patient affected by MC HCV positive withdiscontinuous and partial therapeutic response to the PE treat-ment. Methods. The PE was carried out with the following cellularseparators: AS.TEC and COM.TEC FRESENIUS removing from1 to 1,5 L of plasma/session. It was executed 3 PE/weeks for2 weeks. Only fresh frozen plasma was used as liquid of replace-ment. Results. A 54-year-old man was observed by our Day Hos-pital in the 2005 year for a suspected MC HCV correlated. Clinicaland laboratory investigation were performed in order to make adiagnosis. The patient showed purpura, weakness, arthralgiasaccompanied by fever and symptoms of incipient neuropathy andnephropathy. The cryoglobulins were isolated at 4°C for 72 hoursas reported. Circulating Immune-complex (CIC), Igs and C3 serumconcentrations confirmed the MC diagnosis. The first treatment of

the MC was focused on eradication of HCV by combinedInterferon-Ribavirin drugs. In order to stoop and quickly resolvethe clinical syndrome, the PE procedures was performed asdescribed in the methods. The patient, after an initial response tothe PE treatment, began not responder in the successful PE ses-sions and an immunosuppressive therapy with Cortisone andInterferon was performed. After approximately a year, the patientbegan again the PE therapy returning to respond to the treatment.PE has been continued every periodically 2 months in the courseof the successive years in order to prevent clinical neuropathy andnephropathy. The treatment with PE is still in course. Conclusions.The Plasma Exchange is currently the main treatment of the clini-cal syndrome correlated to MC HCV associated. In fact, thistherapy produce a marked decrease in cryoglobulins levels and asubsequent relevant clinical improvement of the renal and neu-ronal symptoms. The data of our work confirm that in the case ofMC HCV + the PE therapy, even if in discontinuous way, is muchefficacy in order to improve the clinical symptoms by removal theCIC and reducing the overload works of the reticulum-endothelialsystem.

40Adsorptive Granulocyte/Monocyte Apheresis (Adacol-umn) for the Treatment of Rheumatoid ArthritisMottola Maria M., 2Di Domenico Gilda G.,3Tirri Enrico E., 2Nocera Cosimo C., 1Zuccarelli Bruno B.1Immunohematology Service Hospital V. Monaldi,2Immunohematology Service Hospital S. G. Bosco, ASLNaples, 3Rheumatology Division Hospital S. G. Bosco,ASL Naples, Italy

Objectives.The Rheumatoid Arthritis (RA) is a rheumatic diseaseremarkably diffused in Europe. The research of new pharmaco-logical therapies for the RA is founded on the discovery of mol-ecules able to inhibits the release of one or more substances liablefor the inflammatory trial such as the monoclonal antibody anti-TNF-a (Infliximab). In the last years, the Leukocytapheresis(LCAP) has been investigated for the RA treatment whichrespond poorly to drug therapy. Psoriatic arthritis (PA) is a chronicinflammatory rheumatic disease grouped among the spondyloar-thropaties. Reviews from literature for the treatment recommen-dations have been performed and published by members of theGroup for Research and Assessment of Psoriasis and PsoriaticArthritis (GRAPPAA). The aim of the present work has been toassess the efficacy and safety of the adsorptive granulocyte andmonocyte apheresis (GCAP) in four patients affected respectivelyby RA and PA. Patients and methods. We enrolled four patients inthis study. They were 4 females, mean age 54.5, range 35–65. Theprocedures of GCAP have been performed through the Adacol-umn (Otsuka Pharmaceuticals). The apheresis sessions have beenat a frequency of one session/week, over 5 consecutive weeks.Results. The two patients affected by RA were hospitalized by ourRheumatology Division in the 2007, for relapsed RA after 3 yearsof disease free survivor time. In the past, they were treated byPrednisone, Methotrexate and Infliximab, but they became after-wards refractory to these treatments. We have begun the proce-dures of GCAP as reported in the methods. Controls of pre andpost- apheresis leukocyte counts have shown a decrease of about70% of granulocytes, 45% monocytes and 3% lymphocytes. Fur-thermore, after GCAP it was observed a marked decrease ininflammatory cytokines produced by blood leukocytes such asTNF-a, IL1b, IL-6 and IL-8. At the same time, at the end of thetreatment cycles, the patients became again to respond to the

Abstracts A13


pharmacological therapy. The two patients affected by PA werehospitalized by our Rheumatology Division in the 2007, for asevere PA. In the last years, they have performed therapy withCortisone, Methotrexate and Infliximab.The patients were actuallynot responder to the drug therapy and showed diffuse skin psoria-sis and severe pain of the joints. The patients were submitted toselective GCAP according to the protocol reported in themethods. After the 5 sessions therapy, the patients achieved thedisease remission. In particular, they sowed a significant fall inCRP, RF, ANA, ANCA and neutrophils/monocytes levels. Simul-taneously, after about a month from the end of the therapeuticcycle, they returned to respond to the pharmacological therapy.Conclusions. Here, we show for the first time that the GCAPtreatment led to clinical improvement in four patients withrelapsed and refractory RA and PA and, at the same time, it isable to restore the sensibility to the common pharmacologicaltreatments.

41Erythrocytapheresis As Rescue Therapy In A PatientAffected By Polycythemia Vera Treated By Pipobroman1Mottola Maria M., 2Di Domenico Gilda G.,1Tremiterra Emilio E., 1Bencivenga Luigi L.,2Nocera Cosimo C., 1Zuccarelli Bruno B.1Immunohematology Service Hospital V. Monaldi,2Immunohematology Service Hospital S.G. Bosco, ASLNaples. Naples, Italy

Objectives. The Polycythemia Vera (PV) is a familial chronicmyeoprolifarative disorder derived by clonal expansion of trans-formed stem cells. Therapeutic management of the PV is actuallyfounded on phlebotomy and aspirin in low-risk patients, whereashigh-risk patients can also receive cytotoxic therapy. Therapeuticerythrocytapheresis is also performed in selected PV cases. In thepresent work we report the case of a patient affected by PV, intreatment from 2005 with Pipobroman and presenting serious col-lateral effects, up to interrupt the pharmacological treatment.Methods. Erythrocytapheresis (EA) was performed using cellularseparator Fresenius COM.TEC, trough the program of red cellsdepletion. It was executed 1session/weeks for 3 weeks. Results. A69-year-old man was hospitalized by our Hematology Division inthe 2004 where a PV was diagnosed. After some months from thediagnosis, he developed an acute coronary syndrome which fol-lowed a block of right and left branch. At first, the patient wastreated with Interferon 3 MU/3 times to week; this treatment, inconsequence of the considerable collateral effects, was suspendedafter some months. In the January 2005, Pipobroman treatmentwas begun 1 mg/kg/day; this dose was reduced to 0.5 mg/kg/dayafter partial disease remission.The treatment was suspended in theFebruary 2007 for the progressive decrease of the PLT (<50.000/mm3) accompanied from a series of further collateral effects and araising of the Hct 62% (nv: 35/55%) (not responder). The patientwas then candidate to phlebotomy therapy in order to reduce thedanger of a thrombosis, but this therapy was contra-indicatedbecause of his cardiovascular problems. For these reasons, thepatient was treated by erythrocytapheresis as rescue therapy inorder to avoid further reduction of the PLT and hemodynamicdisequilibrium. At the end of the treatments the patient not pre-sented some collateral effect and reached a Hct value of 45% andPLT > 50.000/mm3. At present, the patient is in clinical phase ofremission and submitted to hematological follow-up. Conclusions.The concept of rescue therapy has spread in the last years in the

haematological literature like concept of heroic or last ditch-efforts. The data of our work show that the EA used as a rescuetherapy is a therapeutic tool of high safety and efficacy for the PV,resolving in short time the disease symptom, avoiding the PLTdecrease and allowing the treatment also in an elderly subject withcardiovascular troubles.

42Management of Chronic Inflammatory DemyelinatingPolyradiculoneuropathy (CIPD) By Periodic TreatmentWith Plasma-Exchange: A Case Report1Mottola Maria M., 2Di Domenico Gilda G.,1Clery Massimo M.,1Bevilacqua Pietro P.,2Nocera Cosimo C., 1Zuccarelli Bruno B1Immunohematology Service Hospital V. Monaldi,2Immunohematology Service Hospital S.G. Bosco, ASLNaples. Naples, Italy

Objectives. Chronic Inflammatory Demyelinating Polyneuropa-thies (CIDP) are neurological diseases characterized by demyeli-nation of peripheral nerves with mononuclear cell infiltrates,electrical conduction slowing or block and elevated cerebrospinalfluid protein with no cells. Numerous data of literature have sug-gested that these illness show an immune mediated pathogenesis.Therapeutic strategies are represented by prednisone, immunesuppressive treatment, as well as plasmapheresis and intravenousimmunoglobulins at high doses (IVIg-HD). The role of thePlasma-Exchange (PE) is correlated with published evidence andindicates that it remove from the blood circulation the mediatorsof the inflammatory (antibodies, cytokines, growth factors) beforethey can activate the mechanism of the damage. In this study, wereport a case of a 50-year-old woman affected by CIPD and treatedfrom the 1993 with periodic plasma-exchange according to ourguidelines. Methods. The procedures of PE are been performed bythe following cellular separators: at first CS3000PLUS(BAXTER), successively AS TEC 204 (FRESENIUS). 1 exchangeof plasmatic volume/session was performed, using as liquid of sub-stitution the fresh frozen plasma. Results. A 50-year-old womanwas hospitalized by our hematology division in the 1993 followingsevere difficulty to breathe and to walk. These symptoms are notregressed with prednisone and immune suppressive treatment. Wehave begin the procedures of PE as reported in the methods. Thepatient responded to a cycle of PE of 3 sessions / week for 2 weeksand then 1/month for 1 year. Following such treatment the patientshowed a complete remission of the symptoms. After 10 year, itwas observed a disease relapse, therefore it was necessary toexecute a new PE therapy accompanied by intravenous IgG high-doses. Such therapy was periodically continued every 3 monthsduring the following years. At present, the patient is periodically(every 3 to 6 months) undergone to PE treatment to prevent therelapse of the disease symptoms. Conclusions. Evidence from trialssuggests that plasma-exchange provides significant short-termbenefit in the chronic inflammatory demyelinating polyradiculo-neuropathy (CIPD). Numerous patients respond to repeatedadministrations of IVIg high doses/PE to achieve a completedisease relapse. Here we show that the periodically PE therapy isable to provide long-term benefit of the disease symptoms and toprevent the illness.

AbstractsA14


43Treatment of Thrombotic Thrombocytopenic Purpura(TTP) By Plasma Exchange: Our Experience In a PatientOn Long Term Therapy1Mottola Maria M., 2Di Domenico Gilda G.,2D’Onofrio Marcello M., 1Mininni Vera., 2Nocera CosimoC., 1Zuccarelli Bruno B.1Immunohematology Service Hospital V. Monaldi,2Immunohematology Service Hospital S.G. Bosco, ASLNaples. Naples, Italy

Objectives. Thrombotic thrombocytopenic purpura (TTP) orMoschowitz syndrome is a disorder secondary to a deficiency ofthe ADAMTS13, a plasma zinc metalloprotease (with throm-bospondin type 1 motif, number 13) that cleaves shear stress-activated von Willebrand factor, thereby preventing the occur-rence of von Willebrand factor-platelet interaction in thecirculation. The most successful therapy is the plasma exchange(PE) where the whole plasma volume of the patient is replaced byfresh frozen plasma (FFP) or cryosupernatant. Corticosteroidand/or immunosuppressive treatment are clinically utilized, too. Inthe present study, we report a case of Moschcowitz’s syndromewith severe prognosis, that we have observed and attended fromthe 10th January, 2003. Methods. The PE was performed with cel-lular separator COMTEC (Fresenius), by exchange of 1 plasmaticvolume/session and using as liquid of substitution FFP. Results. A31-year-old woman, with diagnosed TTP, presenting repeated cere-brovascular attacks, organic psychosyndrome, microangiopathichemolytic anemia and thrombocytopenia, obtained a completesyndrome remission (CSR) after ten PE treatments (executedthrough 1 year after the diagnosis). In the 20th July 2006, thepatient was again hospitalised with fever, haemorrhagic and neu-rological symptoms. The following values of laboratory analyseswere identified: Hb: 9,5 g/dl; RBC: 3,18 ¥ 106 mm3; HCT: 27,5%;PLT: 4.9 ¥ 106/mm3; LDH: 1.565 UI/L; Aptoglobin: 5 mg/dl. There-fore, plasmapheresis therapy was immediately executed, in asso-ciation with a corticosteroid and immunosuppressive treatment.The exchange plasmapheresis was performed according to ourprotocols: 1treatment/die for seven days and subsequently to alter-nate days, for a total amount of 10 general sessions. At the end ofthe treatment a CSR was observed and the following values oflaboratory were shown: Hb: 11,0 g/dl; RBC: 3,5 ¥ 106/mm3; HCT:35%; PLT: 316 ¥ 106/mm3; LDH: 400 UI/L; Aptoglobin:128 mg/dl.At the present time, the patient is still alive, the disease’s symptomsare absent and the parameters of laboratory are regular. Conclu-sions. Plasmapheresis is often resolutive and extremely effectivefor primary TTP. In this work, we describe a case of a TTP patientwhich conditions have been resolved with plasmapheresis andcortisone/immunoglobulin therapy. In particular, the PE treatmenthas been effective to induce the CSR in the acute phase of theillness. The analysis of this case suggests the need for an earlydiagnosis, even if this is not easy, in order to commence a successfultherapy.

44Successful Use of Modified 2-Stage Extracorporeal Photo-chemotherapy Procedure in Low Body Weight ChildrenReddy, Ramakrishna L, Tafolla, Kay, Burks, ChristinaAmerican Red Cross Blood Services, Midwest Region,Omaha, NE, USA

Introduction: Extracorporeal Photochemotheraphy (ECP) isused as a salvage therapy for corticosteroid resistant Graft Versus

Host Disease (GVHD) after Hematopoietic Progenitor Cell(HPC) transplantation and in cases of chronic rejection in solidorgan transplants. The Therakos UVAR XTS is approved systemfor ECP in the USA. This is an intermittent blood flow systemwith relatively large extra corporeal volume and cannot be usedin patients with body weights lower than 40 kg, particularly insmall children. We report use of a modified 2-process ECP, wherein WBC are collected on COBE Spectra and UV phototreatedon UVAR XTS and returned to the patient. Methods: 5 children,1 female and 4 male age 3.5–9.5 years, weight 11.8 to 27 kg, had176 treatments. WBC were collected by processing 2 bloodvolumes on COBE Spectra with MNC program. The circuit wasprimed with 1 unit of Adsol RBC, leukoreduced, CMV negative,HbS negative, with a hematocrit 60–65%, with no rinse back.ACDA anticoagulant was used. All patients received infusion of1 gm of calcium gluconate in 50 ml of saline programmed toinfuse over 6 hours or as long as the procedure was running. TheWBC collected was then processed on UVARXTS by 1 cyclewith 125 ml bowl, using a 2nd Adsol RBC unit for collection ofBuffy Coat. UVadex (Methoxsalen) was added to Buffy Coat,phototreated and reinfused to the patient.

Results:

CollectionVolume,ml1st stage

TotalWBC

Collected1st stage 109

CollectionVolume,ml2nd stage

TotalWBC

Collected2nd stage

109

%Recoveryof WBC

WBCinfused106/kg

Mean/Range185

(175–189)5.5

(3.3–9.5)252

(239–265)2.9 (1.7.4.7) 54

(48–71)167

(96–303)

The average dose of treated WBC returned to the patient by twostage procedure was higher compared to 44.9.106/kg (26–74) in anadult patient treated by one stage procedure.All patients toleratedprocedures well. The ionized calcium levels measured at the start,midway, and at the end of the procedure were maintained at anaverage of 1.0.mmol/L, and the patients had no citrate reactions.One patient with bowel transplant and one with HPC transplantGVH died because of disease complication, one HPC patient hadrecurrence of leukemia and discontinued. Two patients with GVHcontinue to have treatments and show improvement of GVH.Conclusion: ECP treatment can safely be performed in low bodyweight children by two stage process. This process delivers moretreated WBC compared to a one stage process used in adults. Thetwo stage process prolongs the treatment time, and requires use ofadditional blood components and calcium infusion. The procedureis well tolerated.

45Adsorption Rate by IgG of IAPP for Multiple SclerosisTakako Iguchi, Satoru Ohji, Miki Kojima,Kouichi Takizawa, Takao Mitsui, Kyoichi NomuraDepartment of Neurology, Saitama medical center,Saitama medical university, Saitama, Japan

Objectives: Steroid pulse therapy is the first-line therapy for mul-tiple sclerosis (MS) in the exacerbation phase; however, somepatients show resistance to steroid therapy (steroid-resistant MS).In the present study, we evaluated the efficacy of immunoadsorp-

Abstracts A15


tion plasmapheresis (IAPP) in patients with steroid-resistant MSand investigated the volume of plasma treated the change in IgGsubclass before and after therapy and the volume of plasmatreated. Subjects and Methods: IAPP was performed in 27 patientswith steroid-resistant MS. We investigated adsorption rate by IgGand the relationship between the volume of plasma treated.Results: Analysis of the volume of plasma treated with IAPPtherapy and IgG subclass showed that IgG1 desorption was foundwith 2,000 mL and that IgG2 and IgG4 desorption was foundwith 1,000 mL. IgG3 desorption was not observed even when thevolume treated exceeded 2,000 mL. Discussion: No report hasaddressed in detail the rate of adsorption of each IgG subclasswith IAPP therapy. Our findings suggest that antibodies maybe adsorbed and removed in the following order: IgG3 > IgG1 >IgG2 = IgG4. IAPP should be performed with consideration of therelationship between IgG subclass of antibodies and the volume ofplasma treated. Conclusion: IAPP is an effective treatment ofsteroid-resistant MS. Further studies will be needed to determineIgG subclass and the optimal volume of plasma treated.

46Novel Therapeutic Strategy for Chronic Hepatitis C:Double Filtration Plasmapheresis and (PEG) Interferon/Ribavirin Combination TherapyTatsuya Ide1, Hidemi Nishida2, Seiya Okuda2,Michio Sata1

1Division of Gastroenterology, 2Division of Nephrology,Department of Medicine, Kurume University School ofMedicine, Japan

Since the double filtration plasmapheresis (DFPP) can reduce thehepatitis C virus (HCV) load in sera, we are conducting the DFPPand (PEG) interferon/ribavirin combination therapy in patientswith chronic hepatitis C. Patients infected with HCV genotype 1band high viral load were enrolled. DFPP were performed three tofive times from the initiation of (PEG) interferon/ribavirin therapywithin two week. We compared the patients with DEPP andwithout DFPP. Mean Log10 reduction of viral load are more than2 log at 4 week in DFPP group. On- treatment virologic responserate of the DFPP group at 12 weeks was higher(62%) than withoutDFPP group (39%). The sustained virological response rate of theDFPP group was higher (72%) than without DFPP group (50%).No serious side effects were observed. DFPP and (PEG)interferon/ribavirin combination therapy was approved in April2008 in Japan and expected to become a new therapeutic strategyfor patients infected with HCV genotype 1 and high viral load.

47World Apheresis Registry 2003–2007 Data: Children andYoung AdultsV. Witt1, B. Stegmayr2, J. Ptak3, T. Nilsson4, G. Berlin5,C.G. Axelsson 6, A. Griskevicius7, P. Centoni8, G.Liumbruno8, P. Molfettini8, J. Audzijoniene7, K. Mokvist4,B. Nilsson Sojka2, R. Norda4, F. Knutson4, W. Ramlow9,M. Blaha10, M. Evergren11, J. Tomaz12

1Department of Haematology and Oncology, St AnnaSpital, Vienna, Austria, 2Department of Internal Medicineand Transfusion Medicine/Blood Center, UniversityHospital, Umea, Sweden, 3Department of Haematology,Regional Hospital, Frydek-Mistek, Czech Republic,4Department of Internal Medicine and Clinical

Immunology & Transfusion, University Hospital,Uppsala, Sweden, 5Blood Center, University Hospital,Linkoping, Sweden, 6Blood Transfusion and ApheresisUnit, Blood Center, University Hospital, Orebro, Sweden,7Therapeutic Apheresis Unit, University Hospital, Vilnius,Lithuania, 8Apheresis Unit, Livorno, Italy, 9Center forApheresis, Rostock, Germany, 10Department ofHaematology, Faculty Hospital, Medical Faculty, CharlesUniversity Hradec Kralove , Czech Republic,11Department of Nephrology, University Hospital,Huddinge, Sweden, 12Immuno-Hemoterapy FacilityHaemapheresis Unit, University Hospital, Coimbra,Portugal

Objectives: The WAA apheresis registry so far contains data from2,013 patients (12448 procedures). This study aims to make suba-nalyses of the data from children and young adults. Methods:This isa web-based registry. A link is available from the WAA homepage(www.worldapheresis.org). So far data from 612 treatments wereregistered in 135 patients who were 21 years or younger and ofthose 308 who were 16 years or younger. Main reason for treatmentwere Stem cell collection due to treatment of various types oftumors (>43%). vasculitis 6%. Results: While adverse events wereregistered in 5.6% of all of the procedures (incl. adults), childrenand young adults had 3.7% and those older than 21 years 6.2%(p = 0.023). Adverse events were similar for those �16 years andthose between 16–21.The treatment was interrupted in 2.3% of theoccasions in the young patients versus 2.7% in the patients above21 years of age. No death occurred due to treatment. More data willbe analyzed and presented.Conclusion:Apheresis in young patientsconstitutes 5% of the activity. There was a lower risk for adverseevents in younger patients. More data will be presented at themeeting

48Effects of Immunotherapies on Anti-MuSK AntibodyPositive Myasthenia GravisShoko Izaki, Misato Takahama, Takashi Tajima,Norihito Yoshida, Masamizu Yamazato, Manabu Onuki,and Kyoichi NomuraDepartment of Neurology, Saitama Medical Center,Saitama Medical University, Saitama, Japan

Case: 24-year-old woman. Chief Complaint: Diplopia, ptosis, dys-phagia, and weakness of the neck and four limbs.Present illness:The patient developed diplopia and ptosis that exhibitedfluctuating nature around the summer of 2005. After developingdysphagia and weakness of the neck and four limbs around March2006, she visited a clinic and was then referred and admitted to ourdepartment in June 2006. On examination, difficulty breathing onexertion, diplopia, bilateral ptosis, and mild weakness of the neckmuscles and proximal limb muscles were observed. Given a posi-tive Tensilon test, negative anti-Ach-R antibody, positive anti-MuSK antibody, and absence of thymoma, the diagnosis wasMuSK -positive MG (15 points on the MGADL scale and Type IIbon the MGFA classification). Although treatment was based onthe use of steroids and tacrolimus, a variety of immunotherapies,including pulse therapy, immunoabsorption plasmapheresis(IAPP) using TR350, double filtration plasmapheresis (DFPP),high-dose intravenous immunoglobulin (IVIg), and simple plasmaexchange (PE: albumin and FFP replacement) were performeddue to recurrent exacerbation of symptoms during the course oftreatment. Results: Pulse therapy and IAPP were not effective

AbstractsA16



while DFPP led to slight improvement of symptoms. IVIg waseffective for diplopia and ptosis. PE was effective for dysphagiaand weakness of the neck muscles, and PP with FFP replacementwas the most effective for the symptoms. Conclusion: Althoughsteroid therapy is the first treatment for MuSK -positive MG,simple PE with FFP was the most effective in the present case.

49Comparison of Some Data Between the Canadian and theSwedish Apheresis RegistryGail Rock, Clas-Göran Axelsson and Bernd Stegmayr forthe Canadian and Swedish Registry members

Comparison of various treatments between the countries may behelpful to understand similarities and differences in the prevalenceof diagnoses and treatment options. The use of prospectivenational and international registries thereby may help in such pro-cesses. Here we start to make some comparisons of data from theCanadian, Swedish and WAA apheresis registries. The number oftherapeutic apheresis procedures that were performed (registra-tion by most centers) yearly are approximately 9500 in 950 patientsof registering centers in Canada and 2145 procedures in 295patients in Sweden (not including stem cell collection). This rep-resents 280 procedures in 28 patients PMP in Canada and 270procedures per million population (PMP) and 37 patients PMP inSweden. The yearly prevalence of patients treated with apheresisfor Thrombotic Thrombocytopenic Purpura are for Canada 4patients PMP (15 treatments as a mean) and 2 patients PMP inSweden (7 treatments as a mean). The figures for acute Guillain-Barré are for Canada 0.5 patients PMP (8 procedures as a mean)and Sweden 0.9 (5 procedures as amean). Extracorporeal Photo-pheresis was performed to the same extent in both countries inabout 1 patient PMP and approximately 20 treatments/patient.Indications were mainly Graft Versus Host disease and CutaneousT Cell Lymphoma in both countries.Although definitions may varyto some extent the severe adverse events were significantly fewerin Canada (0.1% of procedures) than in Sweden (0.5% of proce-dures) and in the WAA registry data, representing mainly Euro-pean centers (0.5% of the procedures, p < 0.001). Conclusion: Thedifferences in TTP may be due to a difference in the incidence ofthe disease, since it may be expected that most patients would havebeen offered this treatment according to guidelines.The differencein the prevalence of patients treated with apheresis for acute GBSmay be due to different treatment traditions. Other similarities anddifferences will be discussed.

50Therapeutic Apheresis in the Neurological DisordersKyoichi NomuraDepartment of Neurology, Saitama Medical Center,Saitama Medical University, Japan

Therapeutic apheresis is divided into cytapheresis and plasmapher-esis. Plasmapheresis (PP) is further divided into three treatments:plasma exchange (PE), double filtration plasmapheresis (DFPP)and immunoadsorption plasmapheresis (IAPP). PE has beenapplied in the several neuroimmunological disorders and effective-ness of PP has been established in some neuroimmunological dis-orders. In the presentation, IAPP treatment of several neurologicaldiseases; Guillain-Barré syndrome (GBS), myasthenia gravis(MG), multiple sclerosis (MS), neuromyelitis optica (NMO) andothers are reviewed. The mechanism of IAPP therapy is not clear.

IAPP is an effective means of removing the pathogenic immune-mediated factors, such as inflammatory cytokines, autoantibodies,immune complexes, and complements. The adsorption ability ofIAPP (TR-350) differs,and has decreased by the IgG subclass of theautoantibody in order of IgG3 (anti-AchR antibody, anti-GQ1bantibody), IgG1(anti-APQ4 antibody), and IgG4(anti-MuSK anti-body). IAPP may affect not only humoral immune responsesbut also cellular immune responses. We have reported that IAPPsuppressed Th1 immune responses and enhanced Th2 immuneresponses, could modulate immunological abnormality. IAPPtherapy may be effective treatment in the neurological diseases.

51Extracorporeal Albumin Dialysis: A Japanese PerspectiveTakaya AbeDivision of Nephrology and Kidney center, KobeUniversity School of Medicine, Hyogo, Japan

The recent development of the blood purification technique hasmade it possible to remove middle molecular weight substancesand even some low molecular weight protein fractions. However,low molecular weight albumin-binding toxins (ABT), such asindoxyl sulfate and bilirubin, are not adequately removed.Albumin has the ability to bind with multiple molecules. Extracor-poreal albumin dialysis (ECAD) is an application of the principleof this ability. Practically speaking, albumin containing bicarbonatedialysate (albumin dialysate; AD) was applied for dialysis, andECAD is defined as extracorporeal therapies using AD and high-flux membrane.The important targets of ECAD are the removal ofnot only water-soluble but also ABT and the recovery of rightfullyfunction of albumin such as carrier protein, antioxidant, and bufferactions. Among ECAD methods, Molecular Adsorption in a Recy-cling System (MARS) might have the largest experience for clini-cal use. The indications for MARS include acute liver failure andacute-on-chronic liver failure. Previous studies have shown thatMARS not only removed ABT but also provide many beneficialeffects on brain, liver, renal, cardiovascular functions, and 30-daysurvival. In Japan, we have not had MARS. We have developed anew original ECAD (Continuous Albumin Purification System:CAPS). However, we have had only few clinical experiences inECAD, because the combination therapy of plasma exchange andcontinuous hemodiafiltration using high-flux membranes has beenprevailing artificial liver support systems. I would like to discussthe basic experiences of AD and the effectiveness for removingalbumin-binding uremic toxins by using AD.

52Extracorporeal Photopheresis (ECP) in the Treatment ofSezary SyndromeJosé Fernández, Mirta AcevedoFLENI, Buenos Aires, Argentina

Background: Mycosis Fungoides and its leukemic variant, Sezarysyndrome (SS), are disorders of malignant, skin homing helper/memory T-cells. SS usually presents with generalized erythrodermaand blood involvement. The endpoint of this study was a �25%improvement in skin score maintained for at least 8 weeks. Partialskin store response (�50%) (PSSR) and complete (�90%)(CSSR), number of ECP treatments, and the time required toachieve 50% improvement in skin involvement were evaluated.Patients and Methods: Twelve patients (pts) with generalizederythroderma (GE) were treated with ECP on 2 consecutive days

Abstracts A17


every 4–5 weeks for 6 months. Patients had received an average of3.2 (range 1–7) prior therapies. Skin improvement was calculatedby comparing baseline skin score to skin scores once a month. Themean baseline skin score of patients was 272 based on a maximumpossible skin score of 400 points. Results: The median follow-up ofthe 12 pts was 1.6 years (range 15 days–2.8 years). Seven pts.achieved a �25% improvement in skin score maintained for atleast 8 weeks (58.3 %). Six pts (50%) achieved PSSR, and 1 pt (8.3%) achieved CSSR. Patients received a median of 28 (range 14–93)treatments. The mean times to reach PSSR were 5.3 � 6 months(median = 6.5). Conclusions: In this short-term, follow-up analysis,ECP was associated with improvement of SS.

Treatment of Rapidly Progressive Glomerulonephritis byProtein A Immunoadsorption: 9 Case ReportsJie Teng, Jianzhou Zou, Yi Fang, Liming Chen, Jun Ji,Xiaoyan Zhang, Shaowei Xu and Xiaoqiang DingDepartment of Nephrology, Zhongshan Hospital, FudanUniversity, Shanghai, China

Objectives: To investigate the efficacy of Protein A immunoad-sorption (IA) on the treatment of rapidly progressive glomerulo-nephritis and its influence on the serum level of antineutrophilcytoplasmic antibody (ANCA) and anti-GBM antibody. Methods:Nine patients (5 female and 4 male) diagnosed with rapidly pro-gressive glomerulonephritis were involved. A median of 5 sessionsof IA were performed. Among them, one was anti-neutrophilcytoplasmic antibody (ANCA) positive with the antigens ofproteinase-3 (anti-PR3), 6 were myeloperoxidase (anti-MPO)positive, and 2 patients had anti-glomerular basement membrane

(anti-GBM) antibody. The mean age was 57.8 � 11.7 years (range43–82). As for the pathological profiles, crescentic glomerulone-phritis accounted for 61.1 � 9.7% of cases. Of those cases, 7 wereaccompanied with type 2 diabetes mellitus and 4 were accompa-nied with interstitial pneumonitis. All of the 9 patients had under-taken IA as well as the drug therapy with glucocorticoids andcyclophosphamides. Results: Serum levels of IgG, anti-MPO, anti-PR3 and anti-GBM antibody were reduced significantly aftera single IA respectively (11.4 � 6.3 vs 7.0 � 4.9, p < 0.001;75.3 � 39.9 vs 51.0 � 27.8, p < 0.05; 10.9 � 2.1 vs 7.4 � 4.5, p < 0.05;23.5 � 24.3 vs 13.0 � 11.6, p < 0.05). Of the three patients whowere dialysis-dependent before IA therapy, two achieved a signifi-cant improvement in renal function, with a reduction of serumcreatinine from 710(mol/L to 350(mol/L and from 624(mol/L to162(mol/L. The remaining six cases also had an improvement inrenal function after IA therapy, as the serum creatinine decreasedfrom 301.7 � 106.2mmol/L to 176.0 � 56.7mmol/L, but withoutstatistical significance. Four patients with pulmonary interstitiallesions all achieved improvements and all of the 9 patients sur-vived. There were no changes in liver function, serum electrolytes,serum glucose, oxygen saturation, hemoglobin, peripheral bloodwhite cell and platelet counts during IA therapy. Patients’ vitalsigns such as blood pressure, heart rate and respiratory rate alsokept steady during each session. Conclusions: For the treatment ofrapidly progressive glomerulonephritis, Staphylococcus protein Aimmunoadsorption therapy combined with pulse therapy of gluco-corticoids and cyclophosphamides significantly reduced serumauto-antibodies such as ANCA and anti-GBM antibody, resultingin an improvement of survival rate and a rapid remission of thedisease.

AbstractsA18


Author Index to Abstracts

The number(s) following the names refer to the number of the abstract.

Abe T 51Acevedo M 52Adamova IY 29, 30, 31, 32Afanasieva MI 30, 31Afanasieva OI 29, 30, 31, 32Arias S 9Atassi-Dumont M 37Audzijoniene J 15, 16, 47Axelsson CG 15, 16, 47Axelsson C-G 49Azmuko AA 30

Baba A 23Begliomini B 3Bencivenga L 41Benedik M 21, 25Berestetskaya YV 31Berlin G 15, 16, 47Berloco PB 7Bespalova JD 31Bespalova ZD 30Bevilacqua P 42Bevini M 3Blaha M 15, 16, 47Bovin NV 29Bren AFBurks C 44Buturovic PJ 21Buturovic-Ponikvar J 25, 26, 27Buturovic-Ponikvar J 10

Caride R 12, 18, 20Cazares R 12, 20Cazarez R 18Ceccarelli S 6Centoni P 15, 16, 47Clery M 42Croxatto JO 9, 19

D’Onofrio M 43De Palma M 3Del Fante C 14, 24Del Principe G 6Di Domenico G 36, 39, 40, 41, 42, 43Dimopoulos MA 4

Eckes J 22Estela R 12, 18Evergren M 15, 16, 47Ezov MV 32

Fernández J 52Ferro J 19Ferro JI 9Fukunaga K 5, 13, 38Furui H 28

Gallo JE 9, 19Gatto S 9, 19Gimeno FL 19Gordillo F 12, 18Grapsa E 1, 4Griskevicius A 15, 16, 47Gubenšek J 21, 25

Hadsell AT 11Haiberger R 7Hara W 34Hida N 38Hofmann JC 8Horie T 28

Ide T 46Iguchi T 2, 34, 45Iida J-I 28Isacchi G 6Isaki S 2Isernia PM 14Izaki S 48

Kamikozuru K 5, 13, 38Kato K 13, 38Kawamura A 28Kersnic B 25Kipor SG 32Kiprov DD 8Klesareva EA 29Knap B 10, 25, 27Knutson F 15, 16, 47Kojima M 45Konovalov GA 32Koo AP 11Korchagina EA 29Kovac J 10, 21, 25, 27Kubota A 34Kukita K 28

Lagouranis A 1, 4Lalic K 15, 16Landolfo A 6Larsson T 16Lastoria C 24Leonardi GM 36Levashov PA 29, 30, 31Liumbruno G 15, 16, 47Luengo F 9

Malavolti R 3Malchesky PS 11Mariano M 3Marn PA 21, 25Marn-Pernat A 10, 26, 27Masini E 39

Author Index to Abstracts A19


Maticas N 1Matsuda Y 33Matsumoto T 5, 13, 35, 38Medina A 12, 18Medina M 20Meguro J-I 28Meloni F 24Meluccio E 39Mininni V 43Mitsui T 2, 45Miwa H 13, 38Mokvist K 15, 16, 47Molfettini P 15, 16, 47Morabito V 7Mottola M 36, 39, 40, 41, 42, 43

Nakamura S 13, 38Narukawa S 34Newman E 15, 16Nilsson SB 15, 16, 47Nilsson T 47Nishida H 46Nocera C 36, 39, 40, 41, 42, 43Nogami K 13, 38Nomura K 2, 34, 45, 48, 50Norda R 15, 16, 47Novelli G 7Novelli S 7Novoa JE 12, 18, 20

Ohda Y 38Ohji S 2, 45Okuda S 46Olivet C 12, 18Onuki M 48Ortega A 12, 18, 20Ouji S 34

Palkeeva ME 30Panagiotou M 1Pandelias K 1Pantelias K 4Papaioannou N 1, 4Pérez CA 12, 18, 20Pérez CF 12, 18, 20Perotti C 14, 24Pham M 8Plachin V 20Pokrovsky SN 29, 30, 31, 32Ponikvar R 10, 21, 25, 26, 27Premru V 26, 27Prophet H 15, 16Psimenou E 4

Ptak J 15, 16, 47Pütz G 22

Ramlow W 15, 16, 47Rangel GR 20Reddy RL 44Rock G 49Rossi M 7Ruberto F 7Rybicki LA 11

Sakata H 28Salvaneschi L 14, 24Sata M 46Schmah O 22Sidorova MV 31Skibinski C 11Soto VM 12, 18, 20Stegmayr B 15, 16, 47, 49Stojkovski L 15, 16

Tafolla K 44Tajima T 48Takahama M 48Takasaki Y 33Takizawa K 45Tamaki T 28Tirri E 40Tomaz J 15, 47Tomaz JN 16Tozawa K 13, 38Tremiterra E 41Tsuda I 28

Varl J 21, 25Viarengo GL 14, 24Villa MA 14

Weisshaar DM 8Wieland H 22Wikström B 15, 16Winkler K 22Witt V 15, 16, 47

Yamaji K 17Yamazato M 48Yokoyama Y 13, 38Yonekawa M 28Yoshida K 38Yoshida N 48Yoshikawa T 23

Zaldini P 3Zuccarelli B 36, 39, 40, 41, 42, 43Žugic R 25, 26, 27

Author Index to AbstractsA20


author index to abstracts

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