Therapeutic plasmapheresis in geriatric patients: favorable results.

Therapeutic plasma exchange is generally a tolerable procedure, although several complications should be considered. Since geriatric population has been growing worldwide, the aim of this study was to retrospectively analyze 4709 TPE data from 981 geriatric procedures (20.8%) and to compare them with 3728 non-geriatric procedures (79.2%). The most common indications for TPE in both groups were sepsis/adult respiratory distress syndrome and multiple organ dysfunction. In geriatric patient group, contrary to expectations of aggravation, complication rate was statistically similar with non-geriatric group (P > 0.05). Therefore, TPE appeared to be a safe procedure in geriatric patients when performed by experienced practitioners.

Therapeutic plasma exchange in treatment of neuroimmunologic disorders: review of 92 cases.

Therapeutic plasma exchange (TPE) is a procedure that reduces amount of circulating antibodies in patients through filtration for the treatment of neurologic diseases in which autoimmunity plays a major role. We reviewed the medical records of 92 neurologic patients who had been consecutively treated by TPE between June 2000 and April 2011 at Ankara University School of Medicine, Neurology Department and The Apaheresis Center. Neurological indications included myastehia gravis (MG, 16 patients), Guillain-Barre syndrome (GBS, 37 patients) and miscellaneous diseases (39 patients). The median TPE session number was 5 with a range of 1-8; total number of TPE procedures in all cases was 454. All MG patients improved with TPE during their hospitalization time. Regarding GBS, nearly 67% of the patients improved early, during their hospitalization time, either. In our series, 25% of GBS cases died because of dysautonomia. TPE was not effective in the treatment of the patients with Lambert-Eaton myasthenic syndrome, paraneoplastic polineuropathy, toxic polineuropathy, mononeuropathy multiplex in the case series. During the TPE procedures, 4 patients had hypotension and total number of the procedures was 21 in those patients. One patient had urticaria in only one session of total 5 TPE procedures. Two patients had septicemia; the first one had 3 and the second had 5 TPE procedures; both septic cases died. In conclusion, TPE is an effective treatment in neurologic diseases that autoimmunity plays an important role in the pathogenesis.

Double filtration plasmapheresis for a case of Crimean-Congo hemorrhagic fever.

Crimean-Congo hemorrhagic fever (CCHF), is a fatal viral infection transmitted to humans through a tick bite or exposure to blood or tissues of viremic hosts. The clinical presentation is characterized by sudden onset high fever, headache, myalgia, abdominal pain and nausea-vomiting followed by gastrointestinal, urinary, respiratory tract and brain hemorrhage. Laboratory findings include leucopenia, thrombocytopenia, elevated liver enzymes, prolonged prothrombin time and activated partial thromboplastin time. We report a case of CCHF who was treated with a combination of DFPP and ribavirin therapy. As a result of this multimodal treatment, patient's clinical symptoms and laboratory findings improved gradually.

Plerixafor use in patients with previous mobilization failure: A multicenter experience.

Plerixafor in conjunction with G-CSF (G-P) is an effective strategy for hematopoietic stem cell mobilization in patients with previously failed mobilization attempt. Here we report our results with G-P among patients with at least one mobilization failure with G-CSF alone (G) or G-CSF plus chemotherapy (G-C). The study included 20 consecutive patients with lymphoma and myeloma from five centers. In 14 (70%) patients, a minimum of 2×10(6)/kg CD34+ stem cells were collected and 16 out of 20 patients (80%) were able to proceed to ASCT. Our study indicates that plerixafor can safely rescue patients with a history of mobilization failure.

Therapeutic plasma exchange in an intensive care unit (ICU): a 10-year, single-center experience.

Therapeutic plasma exchange (TPE) is a blood purification method that effectively allows for the removal of waste substances by separating out plasma from other components of blood and the removed plasma is replaced with solutions such as albumin and/or plasma, or crystalloid/colloid solutions. Plasma exchange therapies are becoming increasingly essential, being used in daily practice in critical care settings for various indications, either as a first-line therapeutic intervention or as an adjunct to conventional therapies. This retrospective clinical study analyzes 10-year therapeutic plasma exchange activity experience in an 18-bed ICU at a tertiary care university hospital with a large, critically-ill patient population. Medical records of 1188 plasma exchange procedures on 329 patients with different diagnoses admitted from January 2000 to July 2010 were evaluated. The aim of the study was to determine the TPE indications and outcomes of the patients who underwent TPE in the ICU with conventional therapy. The secondary endpoints were to determine the differences between different patient groups (septic vs. non-septic indications) in terms of adverse events and procedural differences.

Remission of severe autoimmune bullous disorders induced by long-term extracorporeal photochemotherapy.

Pemphigus vulgaris (PV) and epidermolysis bullosa acquisita (EBA) sometimes resist treatments. In drug-resistant cases, adjuvant treatment with extracorporeal photochemotherapy (ECP) has been reported to induce remission. However, limited numbers of patients have been reported up to date. Eleven patients with drug-resistant autoimmune bullous diseases have been treated with ECP (8 patients with PV, 3 patients with EBA). The introduction of ECP to systemic therapies of the patients with PV resulted in complete response (CR) after a limited cycle (2-6 cycles) in all, except one patient. Prednisolone doses could be tapered in all patients. ECP resulted in CR in two patients while improvement was partial in one patient with EBA after 3-6 cycles. Our patients demonstrate the efficacy of long-term ECP to be tried in the treatment of aggressive autoimmune bullous disorders. The treatment has produced a remarkable corticosteroid-sparing effect while inducing clinical remission.

The effect of CD34 count and clonogenic potential of hematopoietic stem cells on engraftment.

In this study we have determined that the number of the CD34 (+) cells in the grafts that were infused to 48 patients who underwent autologous and allogeneic hematopoietic cell transplantation and evaluated the number of colony forming units in vitro. Our aim was to determine whether there is a relation between these cell counts and post transplantation engraftment kinetics. A negative correlation was detected (p<0.05) between the CD34 (+) cell count and all colony forming units. A correlation between the CD34 (+) cell count and the kinetics of engraftment could not be demonstrated. In the autologous group, only a weak negative correlation between the CFU-GEMM and neutrophil engraftment was detected. In the allogeneic group, colony forming units did not determine the engraftment.

Impact of harvest product volume in erythrocyte depletion of allogeneic or autologous bone marrow using COBE spectra.

UNLABELLED: Depletion of bone marrow (BM) from erythrocytes is used to prevent early hemolysis in major ABO incompatible allogeneic hematopoietic cell transplantation (Allo-HCT). This method was also strongly recommended before storing of autologous and even allo-BM for volume reduction in order to prevent early hemolysis and DMSO toxicity after infusion. In our center, erythrocyte depletion of BM harvests has been performed on a continuous flow cell separator, which used a closed system with a high mononuclear cell (MNC) yield and low rate of erythrocyte contamination. According to the protocol of a cellular therapy approach in a cardiovascular collaborative study we have to adopt the process to lower volumes. We aimed to compare our results with standard volume (SV) (historical control) to low volume ED procedures. PATIENTS AND METHOD: Data has been collected from the last five years. We analyzed 28 cases in the SV group (BM volume >750ml) and 39 cases in the low volume (LV) group. Nineteen of these cases were allogeneic, and 48 were autologous procedures. We used the software COBE PBSC coll vers 5.1 and a standard disposable set (Gambro BCT, Lakewood, USA) for the procedure, and simultaneously, a double bag system with intermediate connectors were used to overcome re-circulation (COBE Spectra Bone Marrow Processing Set, Lakewood USA). RESULTS: The mean volume reduction was 88% (range, 84.4-93.5%) for SV and 90.8% (range, 87.2-91.3%) for the LV group. We did not find any significant difference for MNC yield, volume reduction rate and CD34+ cell recovery between the SV and LV group. There were no complications experienced with regards to device or technical difficulties during procedures. Acute massive intravascular hemolysis was not observed in allogeneic recipients. CONCLUSION: ED and volume reduction with COBE spectra produced successful results in standard and low harvest volumes. This process can be successfully applied to lower volumes and comparable results to the SV harvest can be achieved for the ED rate, reduction of volume and recovery of MNCs and CD34+ cells.

How to calculate the quantity of CD34+ cells infused? A single center cohort study based on actual, ideal or adjusted ideal body weight.

Transplant physicians are generally using the recipient's actual body weight (ABW) for the calculation of the content of CD34+ cells in the harvest material in hematopoietic stem cell transplantation (HSCT). As a reference center performing both the stem cell collection and HSCTs, we aimed to evaluate whether there were any differences for neutrophil recovery by calculating the CD34+ cell content in the graft according to actual, ideal (IBW) or adjusted IBW (AIBW) of the recipients in both autologous (n=148) and allogeneic stem cell collection setting (n=234). We observed a negative correlation between the neutrophil recovery and the cell doses infused as to each of these BWs in the allo-HSCT group, but not in the auto-HSCT group. This negative correlation was stronger for IBW and AIBW rather than for ABW in allo-HSCT group. In addition, calculations for both IBW and AIBW in autologous and allogeneic transplants revealed a significant difference in comparison to ABW for different cut-off values of infused CD34+ cells. Consequently, we suggested that both IBW and AIBW based calculations of CD34+ cells infused are better predictors of neutrophil recovery in comparison to ABW in allo-HSCT. We were not able to show this impact in autologous transplants.

The effect of extracorporeal photoimmunotherapy (ECP) on serum TNF-a level in chronic graft versus host disease (GvHD).

Graft versus host disease (GvHD) is the most prominent cause of morbidity and mortality after allogeneic hematopoietic cell transplantation (Allo-HCT). Extracorporeal photoimmunotherapy (ECP) is an alternative therapeutic modality in steroid and/or cyclosporin-A refractory GvHD developing after Allo-HCT. The aim of this study was to evaluate whether there was any relation between serum TNF-a levels and the response to ECP in patients with steroid refractory of extensive chronic GvHD. Between March 2001 and August 2003, seven patients (male: 1, female: 6) had ECP for treatment of steroid refractory extensive chronic GvHD. Five age and gender matched healthy volunteers were included in this study as the control group. The age of the patients ranged from 18 to 49 years. All patients were allografted from HLA-identical sibling donors. The median number of ECP sessions was 10 (8-36), consisting of two sequential cycles monthly. For measurement of serum TNF-a levels, blood samples were obtained both prior to ECP (basal) and after the first and second in all patients and in five patients after the 10th session. Serum TNF-a levels (Quantakine HS, R&D system, UK) were measured in peripheral venous blood samples by an ELISA method. ECP was given at a median of 5.8 months (1-14 months) after allo-HCT. No complications were seen during or after the ECP procedures. The median time of an ECP session was 183 minutes. The median volume of Uvadex used per session was 4.40 ml (3.61-5.61). The basal mean level of TNF-a was higher in patients than in the control group (2.47+/-0.83 pg/ml vs. 1.75+/-0.06, p=0.05). The mean TNF-a levels decreased from 2.47+/-0.83 pg/ml to 1.77+/-0.93 pg/ml after the initial session (p=0.045) and from 2.32+/-0.92 pg/ml to 1.69+/-0.93 pg/ml after the second day (p=0.015). After completion of the ECP sessions, extensive chronic GvHD recovered in only three patients. In three clinically responsive patients, the TNF-a levels were significantly reduced after both the second and tenth sessions. In contrast, in two patients not responding to ECP therapy, TNF-a levels were increased. In order to report whether these changes in TNF levels is an early predictor for evaluation of the efficacy of ECP in extensive chronic GvHD, TNF-a levels should be studied in a larger series.

Therapeutic plasma exchange in the treatment of neuroimmunologic disorders: review of 50 cases.

Therapeutic plasma exchange (TPE) has been used for the treatment of neurologic diseases in which autoimmunity plays a major role. We reviewed the medical records of our patients who had consecutively been treated by TPE between January 1998 and June 2000. Neurological indications included myasthenia gravis (30 patients), multiple sclerosis attack (6 patients with remitting-relapsing course and 3 patients with secondary progressive course), Guillain-Barrè syndrome (6 patients), paraproteinemic neuropathy (2 patients), and chronic inflammatory demyelinating neuropathy (CIDP), transverse myelitis due to systemic lupus erythematosus, acute disseminated encephalomyelitis in one patient each. Continuous flow cell separators were used for TPE. TPE was generally given every other day for all of the patients and one plasma volume was exchanged for each cycle. Although the patients with secondary progressive multiple sclerosis (3 patients) and paraproteinemic neuropathy (2 patients) did not show any improvement after TPE, other patients' targeted neurological deficits were improved by TPE. During the TPE procedures, no patient had any morbidity or mortality, and the complications were mild and manageable such as hypotension, hypocalcemia and mild anemia; three patients had septicemia due to the venous catheter used for TPE. TPE is an effective treatment in neurologic diseases in which autoimmunity plays an important role in pathogenesis, and it is safe when performed in experienced centers.

Effects of plasma nitric oxide levels on platelet activation in single donor apheresis and random donor concentrates.

P-selectin is an useful marker to determine platelet activation and nitric oxide inhibits platelet activation, secretion, adhesion and aggregation. The aim of this study was to investigate the relationship between nitric oxide and P-selectin values in both single donor apheresis and random donor platelet concentrates. According to the results of this study, we found that the best platelet concentrate is freshly prepared single donor apheresis concentrate and it is important to prevent activation at the beginning of the donation. Nitric oxide, which is synthesized from platelets during the storage period, is not sufficient to prevent platelet activation.

Does continuous flow apheresis influence viability in allogeneic hematopoietic stem cell harvest?

One of the important clinical variables determining the success of hematopoietic stem cell transplantation is the number of viable CD34+ stem cells transfused to the patient. G-CSF mobilized peripheral blood stem cells from 17 healthy donors were collected by continuous flow apheresis. The median (range) proportions of early apoptotic (Annexin V-FITC(pos)/7-AAD(neg)) and viable (Annexin V-FITC(neg)/7-AAD(neg)) CD45(dim)CD34+ stem cells were 1.5 (0.9-3.7)% and 97.7 (82.8-100)% in the peripheral blood before apheresis and 2.6 (0.8-7.9)% and 97.3 (91.9-99)% in the apheresis products, respectively. Despite an increase in the number of apoptotic cells among all cell compartments, this was statistically significant only in CD34+ cells and granulocytes. The majority of the cells still retained their viability.

Effects of replacement fluids used for therapeutic plasma exchange on plasma viscosity and plasma oncotic pressure.

INTRODUCTION: Apheresis is a procedure in which one of the components of blood is removed. The aim of therapeutic plasma exchange (TPE) is to remove a large fraction of the patient's plasma from the body, and to exchange this with replacement solutions using automatic devices. With this procedure circulating pathogens and toxins are reduced. Before each TPE results of a baseline basal complete blood count, serum protein electrophoresis, coagulation tests and serum electrolytes must be known. The efficacy of this therapy is assessed only by these values. The proteins responsible for disease may be monoclonal proteins, cryoglobulins, lipoproteins, auto or allo antibodies or toxins. In this study, we aimed to compare the effects of several replacement fluids on plasma viscosity and oncotic pressure. At the same time, we evaluated the correlation between plasma viscosity and oncotic pressure. MATERIAL AND METHODS: 111 TPE were performed on 42 patients. Before TPE, the patients whose veins were not suitable were catheterised either by using a subclavian or jugular 11F dialysis catheter. At each session, approximately 1-1.5L of plasma was exchanged. The procedure was performed with albumin in patients whose albumin was under 3gr/dl. Over this value, the exchange fluids were randomised. RESULTS: When the overall results were analysed, there was no statistically significant difference between groups 1 (HES+albumin) and group 3 (albumin). The statistical difference between group 2 and 3 was significant, but no difference was observed between group 1 and 2. According to the decreasing plasma viscosity, there was a significant difference between group 2 and group 3, but there was no difference between group 1 and group 2. CONCLUSIONS: The replacement solutions used for plasmapheresis are similar when compared for hemorheologic effects, but we have chosen fresh frozen plasma because of fewer side effects.

Therapeutic plasma exchange in a single center: Ibni Sina experience.

BACKGROUND: The number of therapeutic procedures is increasing steadily year by year with growing collaboration of departments other than Hematology. In the aim to demonstrate our single center activity we analyzed our data since four years. METHODS: Between years 1998 and 2001, 658 therapeutic plasma exchange (TPE) procedures were performed on 158 patients. Median age and male/female ratio were 37 (range, 15-87) and 80/78, respectively. Main indications were myastenia gravis (n=55, 34%), TTP (n=13, 8.5%), post ABO mismatched allogeneic hematopoietic cell transplantation aregeneratoric anemia (n=6, 7.5%), progressive systemic sclerosis (n=10, 6.5%), multiple myeloma (n=10, 6.5%), Gullian Barre Syndrome (n=9, 5.9%), multiple sclerosis (n=7, 4.6%), Waldenström Macroglobulinemia (n=5, 3.4%), polymyositis (n=4, 2.7%), sepsis and disseminated intravascular coagulation (n=4, 2.7%). Departments who referred the majority of the patients for TPE were neurology (n=199), hematology (n=153), immunology (n=78), intensive care unit (n=78) and thorax surgery (n=51). RESULTS: The median TPE procedure per patient was 4 (range, 1-50). All the procedures were performed on continuous flow cell separators and median plasma volume processed per cycle was 2471 ml (range 436-5000). The replacement fluids used were 3% hydroxyethylstarch (HES) (24%), 5% albumin (35%), fresh frozen plasma (25%), and HES and albumin (16%). HES was tolerated well even as a sole replacement fluid with acceptable minor side effects. In three patients with progressing hypoalbuminemia HES was replaced or combined with 5% albumin. Close monitoring of serum albumin and fibrinogen levels after repeated procedures is mandatory. CONCLUSION: In our four years of TPE experience we have increased our collaboration with other departments. 3% HES+/-5% Albumin is a feasible, well tolerated and cost effective replacement fluid combination especially for short-term plasma exchange therapy.

Extracorporeal photoimmunotherapy for the treatment of steroid refractory progressive chronic graft-versus-host disease.

BACKGROUND: Chronic graft-versus-host disease (cGVHD) can arise frequently as a late complication after allogeneic hematopoietic cell transplantation. Patients with extensive disease to date require intensive and long-term immuno-suppression. We aimed to share our single center experience using extracorporeal photoimmunotherapy (ECP) in our steroid refractory extensive cGVHD patients. PATIENTS AND METHODS: Eight patients with a median age 42 (range, 17-43) and M/F: 2/6 were treated with ECP (UVAR XTS) on 2 consecutive days every 2-4 weeks until resolution of GVHD over a period of 6-15 months concomitantly with immunosuppressive agents. Beyond extensive steroid refractory cutaneous cGVHD, three patients had also bronchiolitis obliterans (BO). Skin scores were assessed by an experienced dermatologist. Clinical, laboratory and radiological findings after 4 months of ECP were accepted as response criteria. The patients received in this almost fully automated system mean 261.4 ml buffy-coat was processed within 193 min using UVADEX sterile solution. RESULTS: After a median of 12 cycles of treatment, 6 patients showed a favorable response. ECP was tolerated well only one patient developed Gr4 thrombocytopenia and another patient had a massive GIS bleeding due to an esophageal tear. Reduction in cholestatic parameters was observed in patients with liver cGVHD, improvement in respiratory functions and CT evaluations in two, and reduction in immunosuppressive requirement in all patients. The most impressive result was the reduced need for hospitalization of these patients and improvement of skin lesions. All but one of the skin biopsy scores was also better after ECP. CONCLUSION: As extensive cGVHD is a life devastating disorder, every attempt to improve the quality of life should be evaluated carefully. Our findings suggest that ECP is a safe and effective adjunctive therapy for steroid refractory extensive cGVHD of the skin. ECP will find a place both for the treatment and may be for the prevention of GVHD as well.

Peripheral blood stem cell apheresis for allogeneic transplants: Ibni Sina experience.

BACKGROUND: The rate of utilizing peripheral blood stem cells (PBSC) as a source for allogeneic stem cells is growing rapidly. We aimed to demonstrate our 4 years experience as the largest apheresis center in Turkey and analyzed the content of the apheresis material. PATIENTS AND METHODS: From 1998 to the end of April 2002, 151 leukopheresis procedures were performed on 116 healthy donors (M/F:66/50) with a median age of 30 years (14-53). The HLA identical sibling donors received rhG-CSF 10 microg/kg/day sc. for 4 days and at the 5th day leukopheresis was started until collecting >4 x 10e6/kg CD34+ cells. Two times the donors' total blood volume was processed in 195 min (178-245) on continuous flow cell separators using peripheral venous access. RESULTS: Preapheresis WBC was 51.5 x 10e9/L (range, 13.11-91.3). Mono nuclear cell, CD34 and CD3 quantity of the harvest material were 5.35 x 10e8/kg (range, 0.45-23.46), 6.4 x 10e6/kg (range, 2.49-33.27) and 2.79 x 10e8/kg (range, 0.46-30.95), respectively. We were able to reach the target CD34 count after 1st cycle in 39% and 2nd cycle 61% of the procedures. In all donors with a peripheral blood CD34 count >80/mcl we succeeded to collect enough stem cells with only one leukopheresis. CONCLUSION: Collection of peripheral blood stem cells with continuous flow cell separators is well tolerated, with no mobilization failures or poor mobilizers. We collected high values of CD34+ cells (med. 6.4 x 10e6/kg) at the expense of high CD3+lymphocytes (med. 2.79 x 10e8/kg), which may increase the risk of acute and chronic GVHD after allogeneic hemapoietic cell transplantation.