Treatment of recalcitrant ulcers with allogeneic platelet gel from pooled platelets in aged hypomobile patients.

We evaluated growth factor contents and clinical efficacy of allogeneic platelet gel (PG) prepared with standard blood banking procedures from routine platelet concentrates (PCs) obtained from buffy coats. The PGs were used to treat 11 hypomobile very elderly patients unable to undergo autologous blood processing and previously ineffectively treated with expensive advanced medications for 8-275 weeks. PGs were prepared by platelet activation with human thrombin or commercial batroxobin. Median and range growth factor contents (ng/mL) were: platelet derived growth factor (PDGF-AB/-BB) 112 (31-157) and 20 (3.8-34); transforming growth factor (TGF-ß1/-ß2) 214 (48-289) and 0.087 (0.03-0.28); basic-fibroblast growth factor (b-FGF) 0.03 (0.006-0.214); vascular endothelial growth factor (VEGF) 1.15 (0.18-2.46); epidermal growth factor (EGF) 4.50 (0.87-6.64); insulin-like growth factor (IGF-l) 116 (72-156). In the clinical study, 222 PGs were used within 2 h of activation to treat 14 chronic skin ulcers in the 11 patients. No improvement was seen in 3 patients with 24, 27 and 30 cm(3) ulcers who could be treated for no more than 4, 7 and 8 weeks due to progressively worsening clinical conditions, while 11 ulcers with 3.2 cm(3) median size (range 0.2-3.6) in the remaining 8 patients showed 91 ± 14 % reduction after a median of 12 weeks (range 1-20). Cost of PG treatment (19,976 euro) amounted to about 10% of the ineffective advanced medication hospital reimbursement fees (191,236 euro). This study supports efficacy and feasibility of allogeneic PG to treat recalcitrant ulcers in very elderly hypomobile patients for whom autologous blood processing may be difficult.

Assessment of selective homing and contribution to vessel formation of cryopreserved peripherally injected bone marrow mononuclear cells following experimental myocardial damage.

In view of a potential clinical use we aimed this study to assess the selective homing to the injured myocardium and the definitive fate of peripherally injected labeled and previously cryopreserved Bone Marrow Mononuclear cells (BMMNCs). The myocardial damage (cryoinjury) was produced in 59 rats (45 treated, 14 controls). From 51 donor rats 4.4 x 10(9) BMMNCs were isolated and cryopreserved (slow-cooling protocols); the number of CD34+ and the viability of pooled cells was assessed by flow-cytometry analysis before and after cryopreservation and simulated delivery through a 23G needle. Seven days after injury, BMMNCs were thawed, labeled with PKH26 dye and peripherally injected (20 x 10(6) cells in 500 microl) in recipient rats. Two weeks after experimental injury, the heart, lungs, liver, kidneys, spleen and thymus were harvested to track transplanted cells. Except a small amount in the spleen, PKH26+ cells were found only in the infarcted myocardium of the treated animals. Typical vascular structures CD34+ were found in the infarcted areas of all animals; treated rats showed a significantly higher number of these structures if compared with untreated. Morphological ultra-structural examination of infarcted areas confirmed in treated rats the presence of early-stage PKH26+ vascular structures derived from injected BMMNCs. The estimated mean CD34+ cells loss due to the cryopreservation procedure and to the system of delivery was 0.24% and 0.1%, respectively, confirming the feasibility of the procedure. This study supports the possible therapeutic use of cryopreserved peripherally injecetd BMMNCs as a source of CD34+ independent vascular structures following myocardial damage.

Platelet transfusion trigger in difficult patients.

There is general consensus that a prophylactic pre-transfusion trigger at 10.000 platelets/microL in stable oncohematological patients is as safe as the traditional trigger of 20.000/microL, and that perioperative triggers at 50.000 and 100.000/microL are adequate in most surgical and neurosurgical conditions respectively. Guidelines on the trigger and other issues related to platelet transfusion can be found in nine documents published during 1987-2001 by the National Institutes of Health (NIH), the British Committee on Standardization in Hematology, the Royal College of Physicians of Edinburgh, the College of American Pathologists, the American Society of Anesthesiology and the American Society of Clinical Oncology (ASCO). Although consensus may be less evident on specific triggers for 'difficult' patients, the following triggers, listed by progressively increasing levels, have been proposed in the literature and have found general agreement: a stable oncohematological recipient: 10.000; lumbar puncture in a stable pediatric leukemic patient: 10.000; thrombocytopenia secondary to gpIIb/IIIa receptor inhibitors [corrected]:10.000; bone marrow aspiration and biopsy: 20.000; gastrointestinal endoscopy in cancer: 20.000-40.000; disseminated intravascular coagulation: 20.000-50.000; fiber-optic bronchoscopy in a bone marrow transplant recipient: 20.000-50.000; neonatal alloimmune thrombocytopenia: 30.000; major surgery in leukemia: 50.000; thrombocytopenia secondary to massive transfusion: 50.000; invasive procedures in cirrhosis: 50.000; cardiopulmonary bypass: 50.000-60.000; liver biopsy: 50.000-100.000; a nonbleeding premature infant: 60.000; neurosurgery: 100.000. The proposed values must be considered within the context of careful clinical evaluation of each individual patient, and attention should be given to the power of discrimination of platelet counters at low counts and to the prompt availability of good quality platelet products in the case of emergency.

Platelet transfusion for patients with cancer: clinical practice guidelines of the American Society of Clinical Oncology.

OBJECTIVE: To determine the most effective, evidence-based approach to the use of platelet transfusions in patients with cancer. OUTCOMES: Outcomes of interest included prevention of morbidity and mortality from hemorrhage, effects on survival, quality of life, toxicity reduction, and cost-effectiveness. EVIDENCE: A complete MedLine search was performed of the past 20 years of the medical literature. Keywords included platelet transfusion, alloimmunization, hemorrhage, threshold and thrombocytopenia. The search was broadened by articles from the bibliographies of selected articles. VALUES: Levels of evidence and guideline grades were rated by a standard process. More weight was given to studies that tested a hypothesis directly related to one of the primary outcomes in a randomized design. BENEFITS/HARMS/COST: The possible consequences of different approaches to the use of platelet transfusion were considered in evaluating a preference for one or another technique producing similar outcomes. Cost alone was not a determining factor. RECOMMENDATIONS: Appendix A summarizes the recommendations concerning the choice of particular platelet preparations, the use of prophylactic platelet transfusions, indications for transfusion in selected clinical situations, and the diagnosis, prevention, and management of refractoriness to platelet transfusion. VALIDATION: Five outside reviewers, the ASCO Health Services Research Committee, and the ASCO Board reviewed this document. SPONSOR: American Society of Clinical Oncology

Cost of umbilical cord blood units released for transplantation.

BACKGROUND: A large number of institutions have started programs banking umbilical cord blood (UCB) for allogeneic unrelated-donor and related-donor transplantation. However, limited information is available on the financial issues surrounding these activities. STUDY DESIGN AND METHODS: The aim of this study was to determine the fee per UCB unit released for transplantation that would allow cost recovery after 10 years. Three organizational models were considered suitable to provide units for five UCB transplants per 1 million population per year, a figure that would translate into an annual need for 280 units in Italy. Models A, B, and C included, respectively, seven networked banks, each with an inventory of 1,500 units; two networked banks, each with an inventory of 5,000 units; and one bank with an inventory of 10,000 units. It was estimated that it would take 3 years to develop the cryopreserved inventory and that approximately 3 percent of the inventory could be released and replaced each year during the 7-year interval between the fourth and tenth years of activity. The data on the costs of labor, reagents and diagnostics, disposables, depreciation and maintenance, laboratory tests, and overhead, as well as the operational data used in the analysis were collected at the Milano Cord Blood Bank in 1996. RESULTS: Fees of US $15,061, $12,666, and $11,602 per unit released during the fourth through the tenth years of activity allow full cost recovery (principle and interest) under Models A, B, and C, respectively. CONCLUSION: Although UCB procurement costs compare favorably with those of other hematopoietic cell sources, these results and the current fee of US $15,300 used in some institutions show that UCB is an expensive resource. Therefore, judicious planning of banking programs with high quality standards is necessary to prevent economic losses. The advantages of lower fees associated with the centralized banking approach of Model C should be balanced with the more flexible collection offered by Model A.

The preparation of leukocyte-poor red cells for transfusion by a simple cost-effective technique.

A modification of the microaggregate filtration technique for the production of leukocyte-poor red cell concentrate is described. The modified technique, termed 'spin, cool, and filter', removed leukocytes more efficiently from relatively fresh blood than the original microaggregate filtration procedure. The residual leukocyte content of 4- to 9-day-old units processed by the modified procedure averaged less than 0.4 X 10(9) white cells per unit. The microaggregate filtration technique, supplemented by buffy-coat exclusion, removed more than 93 percent of the units' white cells. These red cell products were prepared easily and did not elicit febrile reactions in highly susceptible patients.