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Biomedical subjects

Thomas H Price

Publications and source records attributed to Thomas H Price.

12 recordsLinked to original sources
PubMed2007

Granulocyte transfusion: current status.

Infection associated with therapy-related neutropenia continues to be a major cause of morbidity and mortality. Renewed interest in granulocyte transfusion therapy as treatment for this condition has been generated by the observation that large doses of granulocytes can be obtained from donors who have been stimulated with granulocyte colony-stimulating factor (G-CSF). Granulocytes collected from these donors have been shown to effectively raise the patient's neutrophil count and appear to function normally as judged both by in vitro and in vivo measures. The evidence for clinical efficacy is limited to that of case reports and small series, and the results are not uniform. Randomized controlled clinical trials are needed to determine whether this therapy is useful in either clearing infections or prolonging survival.

Case-Control Studies↗
PubMed2005

Effective storage of granulocytes collected by centrifugation leukapheresis from donors stimulated with granulocyte-colony-stimulating factor.

BACKGROUND: Donor stimulation with granulocyte-colony-stimulating factor (G-CSF) has increased the number of neutrophils (PMNs) that can be collected for granulocyte transfusion therapy. Clinical utility, however, has been limited by the inability to store functional PMNs ex vivo. This study was conducted to determine whether granulocyte products from G-CSF-stimulated donors could be effectively stored at reduced temperature (22 degrees C vs. 10 degrees C) with maintenance of functional properties in vitro and in vivo. STUDY DESIGN AND METHODS: Nine normal subjects received G-CSF (600 microg subcutaneously) 12 hours before centrifugation leukapheresis. Granulocyte products were divided and stored for 24 and 48 hours under four conditions: 1) 22 degrees C; 2) 22 degrees C, with supplemental G-CSF (100 ng/mL); 3) 10 degrees C; and 4) 10 degrees C, with supplemental G-CSF. Functional PMN activity during ex vivo storage was assessed in vitro and in vivo by the skin-window technique for granulocytes stored at 10 degrees C for 24 hours. RESULTS: Surface expression of CD11b/CD18, CD14, CD16, CD32, and CD64 was maintained during 48-hour storage at reduced temperature. Inducible respiratory burst activity, bactericidal activity, and fungicidal activity were preserved during storage for 48-hour storage at 10 degrees C. Proinflammatory cytokine production was decreased in product stored at 10 degrees C. Supplemental G-CSF ex vivo did not substantially improve functional activity during storage. After storage at 10 degrees C for 24 hours, in vitro chemotactic potential was maintained, and transfused granulocytes retained capacity to circulate and migrate appropriately in vivo. CONCLUSIONS: Granulocyte product collected by centrifugation leukapheresis from G-CSF-stimulated donors can be effectively stored at subphysiologic temperature for 24 hours with preservation of functional activity. Storage at 10 degrees C appears to be slightly superior to storage at 22 degrees C.

Adult↗
PubMed2005

Augmented mobilization and collection of CD34+ hematopoietic cells from normal human volunteers stimulated with granulocyte-colony-stimulating factor by single-dose administration of AMD3100, a CXCR4 antagonist.

BACKGROUND: AMD3100, a selective antagonist of CXCR4, rapidly mobilizes CD34+ hematopoietic progenitor cells (HPCs) from marrow to peripheral blood with minimal side effects. STUDY DESIGN AND METHODS: To further investigate potential clinical utility of AMD3100 for CD34+ cell mobilization and collection, a Phase I study in normal volunteers was performed examining single-dose administration of AMD3100 alone and in combination with a standard 5-day granulocyte-colony-stimulating factor (G-CSF) regimen. RESULTS: AMD3100 (160 microg/kg x 1 on Day 5) significantly increased both G-CSF-stimulated (10 microg/kg/day) mobilization of CD34+ cells (3.8-fold) and leukapheresis yield of CD34+ cells. Moreover, collection of CD34+ cells was comparable between individuals mobilized by a single-dose regimen of AMD3100 (240 microg/kg) and individuals mobilized with a 5-day regimen of G-CSF. AMD3100-mobilized leukapheresis products contained significantly greater numbers of T and B cells compared to G-CSF-stimulated leukapheresis products. CONCLUSION: These findings indicate that AMD3100 can be used alone or as an adjunct to G-CSF to mobilize cells for HPC transplantation.

Anti-HIV Agents↗
PubMed2003

Transfusion-transmitted cytomegalovirus infection after receipt of leukoreduced blood products.

Leukoreduced blood products are reportedly comparable to cytomegalovirus (CMV)-seronegative products for the prevention of transfusion-transmitted CMV (TT-CMV) infection after stem cell (SC) transplantation. To determine if the incidence of TT-CMV was affected by the increasing use of leukoreduced blood products, we followed a prospective cohort of 807 CMV-seronegative SC transplant (SCT) recipients who underwent weekly surveillance using the pp65 antigenemia assay. The incidence of TT-CMV for 2 time periods was recorded: Period 1 (5/94-11/96), when only CMV-seronegative and/or filtered blood products were provided, and period 2 (12/96-2/00), when leukocyte-reduced platelets obtained by apheresis without filtration were also used. The incidence of TT-CMV was higher during period 2 (18/447, 4%) than period 1 (6/360, 1.7%) (P <.05); this was correlated with higher utilization of both filtered and apheresed products from CMV-positive donors in period 2. Multivariable analysis identified filtered red blood cell (RBC) units (but not apheresis platelet products) from CMV-positive donors as the primary predictor of TT-CMV: each additional filtered RBC unit was associated with a 32% increase in the odds for TT-CMV (95% confidence interval [CI]: 8%-61%, P =.006). Pre-emptive therapy with ganciclovir after detection of antigenemia prevented all but one case of CMV disease prior to day 100. CMV-seronegative products may thus be superior to leukoreduced products (particularly filtered RBCs) for the prevention of TT-CMV. In an era of "universal leukoreduction," the abandonment of CMV-seronegative inventories appears premature, particularly among populations at high risk of CMV disease that do not receive active surveillance.

Blood Component Transfusion↗
PubMed2002

Granulocyte transfusion in the G-CSF era.

Granulocyte transfusions have been used since the 1960s with varying degrees of clinical success in the treatment of infection in patients with neutropenia or inherited granulocyte disorders. A number of studies have indicated that efficacy may well be associated with the dose of granulocytes delivered. Collection of granulocytes using modern apheresis machines and corticosteroid administration yields approximately 20 to approximately 30 x 10(9) neutrophils, unlikely to be adequate for treating an established infection. The administration of G-CSF to healthy donors has resulted in average granulocyte yields up to 8 x 10(10) cells. Normal or near normal blood neutrophil counts are often attained when these concentrates are transfused to neutropenic recipients, and these levels are sustained for up to 24 h. G-CSF-primed granulocytes appear to be functionally normal by both in vitro and in vivo measurements. Adverse effects experienced by recipients are similar to those seen with traditional doses of granulocytes. G-CSF administration to donors is well tolerated. Controlled clinical trials are needed to determine the therapeutic efficacy of G-CSF-primed granulocyte transfusions.

Granulocyte Colony-Stimulating Factor↗
PubMed2002

Granulocyte transfusion therapy for infections in candidates and recipients of HPC transplantation: a comparative analysis of feasibility and outcome for community donors versus related donors.

BACKGROUND: Feasibility, response to granulocyte transfusion therapy, and clinical outcome were compared among HPC transplant recipients enrolled in a prospective study of a community blood bank-based unrelated donors program, a prospective granulocyte study using family donors, and matched control patients without granulocyte transfusion therapy. STUDY DESIGN AND METHODS: Overall, 40 patients (327 collections) received granulocyte concentrates from unrelated donors, 34 patients (219 collections) received granulocyte concentrates from related donors, and 74 patients served as controls. Study entry criteria for patients included an absolute neutrophil count (ANC) of less than 200 per microL and documented invasive fungal or bacterial infections. RESULTS: There was a median delay of 3 days (range, 0-14) in patients receiving transfusions from unrelated donors between day of diagnosis of infection and start of granulocyte transfusion therapy as compared with a median delay of 5 days (range, 0-25) in patients receiving transfusions from related donors (p = 0.01). The ANC increment after the first, second, and seventh transfusions in patients who had community donors was significantly higher or comparable to patients who had family donors. Overall, clinical outcome was comparable between the three patient groups. Kaplan-Meier analysis revealed no difference between all cohorts in overall 6-month survival (p = 0.28, log-rank) or event-free survival (p = 0.17, log-rank). CONCLUSION: These results suggest that future efficacy trials should consider inclusion of unrelated community donors for timely institution of granulocyte transfusion therapy.

Adolescent↗
PubMedDate not supplied

Use of cellular and plasma apheresis in the critically ill patient: part 1: technical and physiological considerations.

Apheresis is the process of separating the blood and removing or manipulating a cellular or plasma component for therapeutic benefit. An apheresis procedure, or series of procedures, may be indicated in the critical care setting as primary or adjunctive therapy for certain hematologic, neurologic, renal, and autoimmune/ rheumatologic disorders. Optimal management of severely ill patients undergoing apheresis requires a working knowledge of the technical, methodological, and therapeutic considerations. These considerations include instrument hardware and separation methods, vascular access requirements, hemodynamic and hemostatic effects of the procedures, exposure to anticoagulants and homologous blood products, physiological variables affecting blood/plasma processing efficiency, and therapeutic endpoints for specific indications. Part 1 of this review will discuss each of those technological considerations and the basic physiological principles that guide this form of therapy. Part 2 of this series will deal with the clinical indications and applications for specific disorders that are most likely to affect patients in the intensive care unit.

Anticoagulants↗
PubMedDate not supplied

Use of cellular and plasma apheresis in the critically ill patient: Part II: Clinical indications and applications.

Apheresis is the process of separating the blood and removing or manipulating a cellular or plasma component for therapeutic benefit. Such procedures may be indicated in the critical care setting as primary or adjunctive therapy for certain hematologic, neurologic, renal, and autoimmune/rheumatologic disorders. In part I of this series, the technical aspects of apheresis were described and the physiologic rationale and clinical considerations were discussed. This review highlights the pathophysiologic basis, specific clinical indications, and treatment parameters for disorders that more commonly require management in the intensive care unit. The choice of plasma or cellular apheresis in these cases is guided by well-accepted, evidence-based clinical treatment guidelines. For some disorders, such as liver failure, severe sepsis, and multiple-organ dysfunction syndrome, apheresis treatment approaches remain experimental. Ongoing studies are investigating the potential utility of conventional plasma exchange, ex vivo plasma manipulation, and newer technologies for these and other disorders in severely ill patients.

Adult↗