Comparison of automated erythrocytapheresis versus manual exchange transfusion to treat cerebral macrovasculopathy in sickle cell anemia.

BACKGROUND: Chronic exchange transfusion is effective for primary and secondary prevention of stroke in children with sickle cell anemia (SCA). Erythrocytapheresis is recognized to be the most efficient approach; however, it is not widely implemented and is not suitable for all patients. The aim of our study was to compare automated exchange transfusion (AET) with our manual method of exchange transfusion and, in particular, to evaluate the efficacy, safety, and cost of our manual method. STUDY DESIGN AND METHODS: Thirty-nine SCA children with stroke and/or abnormal findings on transcranial Doppler were included in the study. We retrospectively analyzed 1353 exchange sessions, including 333 sessions of AET and 1020 sessions of manual exchange transfusion (MET). RESULTS: Both methods were well tolerated. The median decrease in hemoglobin (Hb)S per session was 21.5% with AET and 18.8% with our manual method (p < 0.0001) with no major increase in red blood cell consumption. Iron overload was well controlled, even with the manual method, with a median (interquartile range) ferritin level of 312 (152-994) µg/L after 24 months of transfusions. The main differences in annual cost relate to equipment costs, which were 74 times higher with the automated method. CONCLUSION: Our study shows that continuous MET has comparable efficacy to the automated method in terms of stroke prevention, decrease in HbS, and iron overload prevention. It is feasible in all hospital settings and is often combined with AET successively over time.

Erythrocytapheresis compared with whole blood phlebotomy for the treatment of hereditary haemochromatosis.

BACKGROUND: Hereditary haemochromatosis may result in severe organ damage which can be prevented by therapy. We studied the possible advantages and disadvantages of erythrocytapheresis as compared with phlebotomy in patients with hereditary haemochromatosis. MATERIALS AND METHODS: In a prospective, randomised, open-label study, patients with hereditary haemochromatosis were randomised to bi-weekly apheresis or weekly whole blood phlebotomy. Primary end-points were decrease in ferritin levels and transferrin saturation. Secondary endpoints were decrease in haemoglobin levels, discomfort during the therapeutic procedure, costs and technicians' working time. RESULTS: Sixty-two patients were included. Thirty patients were randomised to apheresis and 32 to whole blood phlebotomy. Initially, ferritin levels declined more rapidly in the apheresis group, and the difference became statistically highly significant at 11 weeks; however, time to normalisation of ferritin level was equal in the two groups. We observed no significant differences in decline of transferrin saturation, haemoglobin levels or discomfort. The mean cumulative technician time consumption until the ferritin level reached 50 µg/L was longer in the apheresis group, but the difference was not statistically significant. The cumulative costs for materials until achievement of the desired ferritin levels were three-fold higher in the apheresis group. CONCLUSION: Treatment of hereditary haemochromatosis with erythrocytapheresis instead of whole blood phlebotomy results in a more rapid initial decline in ferritin levels and a reduced number of procedures per patient, but not in earlier achievement of target ferritin level. The frequency of discomfort was equally low with the two methods. The costs and, probably, technician time consumption were higher in the apheresis group.

Determining factors predictive of CD34+ cell collection efficiency in an effort to avoid extended and repeated apheresis sessions.

INTRODUCTION: Collection efficiency (CE) is a reflection of the proportion of cells passing through a cell separator that is harvested. The aim of our study was to evaluate which factors influence CE independently in order to find ways to improve CE and therefore minimize the costs and risks of leukapheresis and graft processing. MATERIALS AND METHODS: A total of 206 consecutive apheresis procedures performed on 128 donors/patients were studied retrospectively. We explored the association between CE and the following factors: age, sex, weight, mobilization (granulocyte-colony-stimulating factor with or without chemotherapy), collection type (autologous versus allogeneic), venous access (peripheral versus central), total processed blood volume (TPV), hematocrit, white blood cell (WBC) count, thrombocyte count, and peripheral blood CD34+ cell concentration (PBCD34+). RESULTS: Stepwise multiple regression analysis showed WBC count to be the single best predictor of CE, accompanied by TPV. When performing subgroup analysis for autologous apheresis procedures, the inverse correlation of WBC count and TPV with CE becomes stronger (r = -0.563 with P < 0.001 and r = -0.198 with P = 0.020 respectively), whereas those correlations disappear when analyzing only allogeneic apheresis procedures. CONCLUSION: The negative correlation between TPV and CE present only in autologous collection procedures can be explained by the limited intra-apheresis recruitment of CD34+ cells into the blood which is negatively influenced by extensive pre-treatment. As a result of this study we decided to limit TPV to a maximum of three times the patient's blood volume in autologous apheresis procedures at our center.

Transfusion immunomodulation--the case for leukoreduced and (perhaps) washed transfusions.

During the last three decades, a growing body of clinical, basic science and animal model data has demonstrated that blood transfusions have important effects on the immune system. These effects include: dysregulation of inflammation and innate immunity leading to susceptibility to microbial infection, down-regulation of cellular (T and NK cell) host defenses against tumors, and enhanced B cell function that leads to alloimmunization to blood group, histocompatibility and other transfused antigens. Furthermore, transfusions alter the balance between hemostasis and thrombosis through inflammation, nitric oxide scavenging, altered rheologic properties of the blood, immune complex formation and, no doubt, several mechanisms not yet elucidated. The net effects are rarely beneficial to patients, unless they are in imminent danger of death due to exsanguination or life threatening anemia. These findings have led to appeals for more conservative transfusion practice, buttressed by randomized trials showing that patients do not benefit from aggressive transfusion practices. At the risk of hyperbole, one might suggest that if the 18th and 19th centuries were characterized by physicians unwittingly harming patients through venesection and bleeding, the 20th century was characterized by physicians unwittingly harming patients through current transfusion practices. In addition to the movement to more parsimonious use of blood transfusions, an effort has been made to reduce the toxic effects of blood transfusions through modifications such as leukoreduction and saline washing. More recently, there is early evidence that reducing the storage period of red cells transfused might be a strategy for minimizing adverse outcomes such as infection, thrombosis, organ failure and mortality in critically ill patients particularly at risk for these hypothesized effects. The present review will focus on two approaches, leukoreduction and saline washing, as means to reduce adverse transfusion outcomes.

The impact of a regular erythrocytapheresis programme on the acute and chronic complications of sickle cell disease in adults.

Thirteen adult patients aged 22-63 (median 30) years with sickle cell disease (SCD) were enrolled in a regular erythrocytapheresis (ECP) programme at a single institution between December 1998 and November 2008. The indications for enrolment were recurrent painful crises (PC), acute chest syndrome (ACS), silent cortical ischaemia, pulmonary hypertension, multi-organ crises and pregnancy. Endpoints retrospectively evaluated included the incidence of SCD-related acute events requiring hospitalization following and prior to regular ECP, the development of new and progression of pre-existing related end-organ damage, the effectiveness in reducing HbS levels acutely and prior to the next exchange and the transfusion-related complications. Sixteen acute sickle-related events occurred in five patients in 846 months of patient follow-up. In all patients with reliable data available pre-ECP, the frequency of such events was reduced following commencing regular ECP. No patient experienced stroke, multi-organ crises or developed new and/or progression of end-organ dysfunction. Regular ECP reduced HbS levels to the target of <30% immediately post-exchange. Alloimmunization rates were comparable to the literature and ECP was effective in preventing progressive iron overload. Regular ECP was demonstrated to be an effective, well-tolerated therapy for both acute and chronic complications of SCD in adults.

Erythrocytapheresis plus erythropoietin: an alternative therapy for selected patients with hemochromatosis and severe organ damage.

We report the efficacy, tolerability and cost of erythocytoapheresis plus recombinant human erythropoietin (rHuEPO) in three patients with severe hereditary hemochromatosis (HH). Results indicate that this regimen could be a valid therapeutic alternative in complicated HH patients. Its cost, however, limits its use to patients whose clinical conditions prevent a proper phlebotomy regimen.

Multicomponent collection as of 2005.

Multicomponent apheresis (MCA) begun in Genoa in 1985 in autologous terms. Named "sequestration" it was the preoperative collection of autologous components (RBC-plasma-platelets) using the same apparatus and harness ready for intraoperative blood salvage. In 1986 the technique was applied to donor platelet apheresis with the goal of reducing the costs of platelet collection and concurrently reducing the risks of viral disease transmission to haematological patients who did receive, in the same transfusion event, the necessary blood components obtained from the same donor. The results of this application were maximized by the so called aggressive MCA by which in selected donors, it is possible to collect 2 units of platelets along with 1 or 2 units of PRBCs. These applications were made possible by the development of the concept of dry-platelet collection according to which platelets are collected in only 20-25 mL of plasma and subsequently resuspended in non-plasma solutions such as T-Sol. A last development of MCC is for RBC apheresis, with the collection of 1-2 units of RBC independently of platelet collection. This is going to be the first step of apheresis as the unique modality of collecting blood leaving the bags to history of blood transfusion. Interestingly it took 15 years to MCC to be rediscovered and appreciated worldwide both for its intrinsic cost saving capabilities offered along with an increasing safety for patients. In terms of donor acceptance it is our experience that, since 1989 no donor has refused MCC, consisting at least in the concurrent collection of plasma along with platelets, but also RBC and or a second unit of platelets.

Cost of autologous peripheral blood stem cell transplantation: the Norwegian experience from a multicenter cost study.

High-dose therapy with autologous blood progenitor cell support is now routinely used for patients with certain malignant lymphomas and multiple myeloma. We performed a prospective cost analysis of the mobilization, harvesting and cryopreservation phases and the high-dose therapy with stem cell reinfusion and hospitalization phases. In total, 40 consecutive patients were studied at four different university hospitals between 1999 and 2001. Data on direct costs were obtained on a daily basis. Data on indirect costs were allocated to the specific patient based on estimates of relevant department costs (ie the service department's costs), and by means of predefined allocation keys. All cost data were calculated at 2001 prices. The mean total costs for the two phases were US$ 32,160 (range US$ 19,092-50,550). The mean total length of hospital stay for two phases was 31 days (range 27-37). A large part of the actual cost in the harvest phase was attributed to stem cell mobilization, including growth factors, harvesting and cryopreservation. In the high-dose chemotherapy phase, the most significant part of the costs was nursing staff. Average total costs were considerably higher than actual DRG-based reimbursement from the government, indicating that the treatment of these patients was heavily subsidized by the basic hospital grants.

Erythrocytapheresis limits iron accumulation in chronically transfused sickle cell patients.

Cerebrovascular accidents (CVA) as a complication of sickle cell disease occur most frequently in childhood. Life-long transfusion prevents recurrent stroke, but inevitably leads to iron overload. Although effective chelation exists, many patients are not compliant. Erythrocytapheresis, an automated method of red blood cell exchange, was evaluated as an alternative to control transfusion-related iron load. Eleven patients with sickle cell anemia and a history of stroke were converted from simple transfusion to pheresis. Total time on pheresis for the group averaged 19 months (range 4-36 months). No significant complications occurred with a mean pre-pheresis hemoglobin S (Hb S) level of 44%. Blood utilization increased by an average of 50%. The effect of pheresis on serum ferritin depended on the patient's pre-pheresis ferritin level and chelation regimen. Ferritin levels remained stable for chelated patients with ferritin levels > or = 5,000 ng/ml, but decreased in a chelated patient with a pre-pheresis ferritin level of 4,000 ng/ml. For non-chelated patients with significant pre-pheresis iron load, ferritin levels remained stable. No patient on chelation prior to pheresis was able to discontinue deferoxamine. However, one patient with pre-pheresis ferritin of 500 ng/ml maintained serum ferritin levels < 200 ng/ml for 36 months of pheresis without chelation. Pheresis is more expensive than simple transfusion unless the cost of chelation and organ damage from iron overload are considered. Erythrocytapheresis is a safe method of controlling Hb S levels and limiting or preventing iron load in chronically transfused sickle cell patients.

Erythrocytapheresis can reduce iron overload and prevent the need for chelation therapy in chronically transfused pediatric patients.

PURPOSE: This research was undertaken to determine the advantages, complications, costs, and efficacy of erythrocytapheresis in young pediatric patients who receive chronic erythrocyte transfusion therapy. PATIENTS AND METHODS: We retrospectively analyzed data for 10 children who received erythrocytapheresis for an average of 16 months. Erythrocytapheresis was compared to simple transfusion therapy with respect to annual blood unit exposure, occurrence of alloimmunization, and costs. Serum ferritin levels were compared before and after the period of erythrocytapheresis. RESULTS: Erythrocytapheresis was well tolerated, even in children as young as 5 years or as small as 20 kg. It required a greater annual unit exposure than simple transfusions, but did not increase alloimmunization. Ferritin levels decreased significantly in children receiving concurrent deferoxamine, and decreased or stabilized in those not on chelation therapy. Children started on erythrocytapheresis soon after stroke have not developed iron overload. Although the costs of erythrocytapheresis exceed that of simple transfusion, the substantial costs of deferoxamine therapy should be considered; one child on erythrocytapheresis has been able to discontinue chelation therapy following normalization of his ferritin level. CONCLUSION: Erythrocytapheresis is a safe and effective method for young patients receiving chronic erythrocyte transfusions. Erythrocytapheresis can reduce total iron burden and may obviate the need for expensive chelation therapy.

[Intraoperative autotransfusion and use of cell saver systems]. / Intraoperative Autotransfusion und Verwendung von Cell-Saver-Systemen.

In the last two years we have performed intraoperative autotransfusion by a cell-saving-system in 46 patients causing a 70%-reduction in the need of homologous blood transfusion. 20% of these patients did not need homologous blood at all. Besides minimizing transfusion-associated risks, intraoperative autotransfusion had an evident cost-sparing effect.

[Cost of intensive treatment followed by autograft of circulating stem cells. Application to multiple myeloma]. / Coût d'un traitement intensif suivi d'une autogreffe de cellules souches circulantes. Application au myélome multiple.

OBJECTIVES: Legitimate efforts to reduce health care costs, especially of intensive protocols including transplantation for haematological diseases, require realistic economic evaluations. We determined the direct cost of intensive chemotherapy associated with total body irradiation and autologous blood stem cell transplantation in patients with multiple myeloma. METHODS: Ten consecutive patients (7 males, 3 females) with Stage II or II multiple myeloma, who had received no prior treatment and were under the age of 55, were included in the study. Peripheral blood stem cells were collected by successive cytaphereses after a short period of aplasia induced by a CHOP protocol. During this period, the patients were in normal hospital rooms. A VAMP protocol was then administered in three 4-day sessions. Intensive therapy was started 1 month later with CCNU, etoposide, cyclophosphamide and melphalan. Total body irradiation (12 Gy) was performed on days -3, -2, -1. Autologous grafting was done on day 0. The intensive therapy was followed by a period of aplasia and the patients were protected in laminar flow rooms. Regular antibiotic and haematologic protocols were applied. Growth hormone was not given. The patients were seen regularly for follow-up and interferon alpha 2b was prescribed for 5. RESULTS: The mean cost of the two year treatment was 468,392 +/- 167,467 French francs. Personnel accounted for 36% of the total cost, marrow collection 13%, blood products 9.8%, laboratory tests 8.2% and drugs 7.2%. Little data are available in the literature of comparable cost analyses in other French hospitals or in other countries. CONCLUSION: Controlled cost/benefit studies should be conducted to enable a rigorous comparison between different therapeutic strategies.