Hematopoietic progenitor cells.
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Animals↗
Biomedical subjects
S F Leitman
Publications and source records attributed to S F Leitman.
A controlled comparison of the efficacy of hetastarch and pentastarch in granulocyte collections by centrifugal leukapheresis.
Compared with hetastarch (HS), the low molecular weight analog pentastarch (PS) has been reported to be equally effective for granulocyte collection by centrifugal leukapheresis, to result in fewer adverse donor reactions (ADR), and to have a more rapid elimination profile. We prospectively compared the granulocyte collection efficiency (GCE), granulocyte yield, and ADR in 72 randomly paired granulocytapheresis procedures from 36 volunteer donors using the model CS-3000 Plus Blood Cell Separator (CS) and either PS or HS as the sedimenting agent. Paired collections from each donor allowed us to compare the two agents directly while controlling for intrinsic donor differences. In 33 of 36 (92%) donors, HS procedures were significantly more efficient than PS procedures (P < .001). As an average, HS collections yielded 2.3 +/- 0.67 x 10(10) granulocytes at 58% +/- 8.8% GCE, whereas PS procedures resulted in 1.4 +/- 0.76 x 10(10) granulocytes at 33% +/- 15% GCE. No starch-induced ADR were seen with either agent. For granulocyte harvests using the CS, (1) in most donors, using HS as the red blood cell sedimenting agent during centrifugal leukapheresis results in significantly higher (nearly twofold) GCE and larger granulocyte yields in comparison with using PS, (2) ADR were not observed with either agent, and (3) the potential benefit of more rapid PS elimination should be balanced against significantly lower granulocyte yields.
Adsorption↗
Efficacy of pentastarch in granulocyte collection by centrifugal leukapheresis.
The efficacy of 6% hydroxyethyl starch (hetastarch, HS) in enhancing granulocyte harvest by centrifugal leukapheresis has been described by a simple equation which predicts the granulocyte collection efficiency (GCE) based on an intrinsic donor variable, the erythrocyte sedimentation rate (ESR): GCE(%) = 1.3 ESR (mm/hr) + 45. Ten percent low molecular weight hydroxyethyl starch (pentastarch, PS) has been reported to be as effective as HS with potentially fewer adverse donor reactions (ADR). The derivation of an analogous equation for PS under conditions previously reported for HS may quantify PS efficacy and allow comparison to HS. We prospectively measured the in vitro and the in vivo effects of PS on the donor ESR in 53 granulocyte collections from 44 donors using the model CS-3000 Plus blood cell separator (CS). We then correlated the findings with the GCE of each procedure and derived an equation which expresses GCE in terms of baseline donor ESR. The in vitro addition of PS increased the donor ESR 2.4-fold, but its administration to a donor during a collection procedure did not appreciably change the ESR. Higher baseline donor ESR was more likely to result in more efficient cell collections: GCE (%) = 0.8 ESR (mm/hr) + 20; (r = 0.37). For granulocyte harvests using the CS and PS as the sedimenting agent 1) baseline donor ESR affects granulocyte harvests, but the poor correlation does not allow an accurate prediction of GCE and cell yield from the baseline donor ESR; 2) in comparison with HS (results from a previous study), PS may be less effective in vitro and not effective in vivo in elevating ESR, and may be less effective in enhancing granulocyte harvest; and 3) the parameters (slope, y-intercept, correlation coefficient) which define the linear relationship between baseline donor ESR and GCE may serve collectively as a quantitative measure of the effectiveness of different hydroxyethyl starch agents in enhancing granulocyte harvests. These parameters may be helpful in rapidly assessing the clinical efficacy of new, potentially useful hydroxyethyl starch agents prior to initiating a randomized, controlled clinical trial.
Blood Sedimentation↗
Lack of sensitivity of indium-111 mixed leukocyte scans for active disease in Takayasu's arteritis.
OBJECTIVE: Currently, a reliable, noninvasive means of detecting the active vasculitic lesions of Takayasu's arteritis does not exist. Based on the cellular infiltrates seen in active lesions, we postulated that indium-111 labelled mixed leukocytes could be used to scintigraphically detect sites of active vasculitis. METHODS: Fifteen In-111 mixed leukocyte scans were performed in 10 patients with Takayasu's arteritis and correlated with clinical, laboratory, and radiographic findings. Patients had either active, stable/smoldering, or inactive disease at the time when 8, 4, and 3 scans were performed, respectively. RESULTS: Two of the 8 scans performed in patients with active disease were positive for increased vessel uptake (sensitivity = 25%). All other scans were interpreted as negative for active arteritis. CONCLUSION: We conclude that In-111 mixed leukocyte scans have a low sensitivity for detection of active Takayasu's arteritis.
Adult↗
Localization of 111indium-labeled tumor infiltrating lymphocytes to tumor in patients receiving adoptive immunotherapy. Augmentation with cyclophosphamide and correlation with response.
BACKGROUND: The adoptive transfer of interleukin-2 (IL-2)-cultured tumor infiltrating lymphocytes (TIL) can cause tumor regression in patients with metastatic melanoma. METHODS: Thirty-eight patients with metastatic melanoma receiving high dose IL-2 and TIL were studied for the ability of autologous 111In-labeled TIL to localize to metastatic tumor deposits by gamma camera imaging and biopsy. Single bolus cyclophosphamide was administered 24-36 hours before TIL infusion in 27 treatment courses. RESULTS: Tumor localization by 111In-labeled TIL was seen by gamma camera imaging in 26 (68.4%) treatment courses. In a univariate analysis of factors influencing TIL traffic, cyclophosphamide administration was significantly associated with the ability to localize tumor by radionuclide imaging (P2 = 0.026). Twenty-one of 26 (80.8%) treatment courses given with cyclophosphamide demonstrated tumor localization, compared with only 5 of 12 (41.7%) treatment courses without cyclophosphamide. In addition, patients whose 111In-labeled TIL imaged their tumor received significantly more TIL than did those that did not (P2 = 0.0052). Biopsies revealed a greater accumulation of 111In in cutaneous tumors than in normal skin biopsy specimens (0.0021 and 0.0004% injectate/gram of tissue, respectively; P2 = < 0.001). The median tumor-to-normal-skin ratio of simultaneous biopsies was 5.0. Finally, 10 of 26 (38.5%) patients who had tumor localization by scan had a clinical response, whereas no responses were noted in 12 patients whose tumors were not imaged (P2 = 0.022). CONCLUSIONS. Localization in tumor may be important in the mechanism of TIL antitumor activity because no clinical responses were seen in patients who did not have their tumors imaged with 111In-TIL. Cyclophosphamide administration before TIL and IL-2 therapy and the administration of large numbers of TIL appear to improve the frequency of TIL localization to tumor.
Adolescent↗
Guidelines for blood utilization review.
Hospitals are required by accrediting agencies to perform blood utilization review. Specific areas that must be addressed are the ordering, distribution, handling, dispensing, and administration of blood components. Monitoring the effects of transfusion on patients is also required. The format of the review process and the criteria for appropriate blood utilization must be developed by each institution. This article provides examples of areas that can be reviewed and procedures that may be used. However, the suggested laboratory values must not be interpreted as defining indications or criteria for transfusion. Each transfusion committee, or its equivalent, is responsible for developing its own institutional blood utilization procedures and audit criteria. Review and approval by the medical staff prior to implementation are essential. The procedures must also be reviewed and revised on a regular basis.
Blood Transfusion↗
Treatment with intralesional granulocyte instillations and interferon-gamma for a patient with chronic granulomatous disease and multiple hepatic abscesses.
We present the case of a 16-year-old girl with p22-deficient chronic granulomatous disease in whom multiple hepatic abscesses secondary to Staphylococcus aureus infection developed. Infection persisted despite extensive surgery and aggressive antibiotic therapy. Conventional intravenous granulocyte transfusions were not tolerated because of the development of alloantibodies to HLA. Treatment with interferon-gamma and intralesional granulocyte infusions was associated with dramatic clinical and radiographic improvement. No morbidity was associated with this therapy. To our knowledge, this is the first report of treatment with intralesional granulocyte instillations. Intralesional granulocyte instillation in association with interferon-gamma administration may result in clinical improvement in the conditions of patients with chronic granulomatous disease and hepatic abscesses for whom conventional therapy has failed.
Adolescent↗
Characteristics of red cells irradiated and subsequently frozen for long-term storage.
Irradiation of blood components eliminates the risk of transfusion-associated graft-versus-host disease. Freezing directed or rare red cell units that are irradiated but not transfused would facilitate inventory management and would increase the transfusion options for the involved patients. However, no studies have been performed to evaluate whether prestorage irradiation damages subsequently frozen red cells. Ten normal volunteers donated a unit of whole blood on two separate occasions. One unit was irradiated with 15 Gy (1500 rad), stored at 4 degrees C for 6 days, and then frozen and stored at -75 degrees C for 56 days. The other unit (control) was similarly stored but was not irradiated. Aliquots of the units were tested on Day 0 and Day 6 and, after deglycerolization, on Day 62. Comparison of means and changes in means showed no significant differences in red cell ATP, 2,3 DPG, or supernatant hemoglobin and glucose in control and irradiated units. The difference in the change in supernatant potassium from Day 0 to Day 6 in control and irradiated units was significant (1.5 to 28.6 mmol/L vs. 1.5 to 48.5 mmol/L: p < 0.0001). Irradiation did not cause significant differences in postdeglycerolization red cell recovery (control, 84.5% vs. irradiated, 81.2%) or in 24-hour posttransfusion autologous red cell survival (control, 91.1% vs. irradiated, 90.9%). Red cells can be irradiated, stored at 4 degrees C for 6 days, and subsequently frozen with no increase in detectable damage as compared to controls that were not irradiated.
Blood Preservation↗
Dose, dosimetry, and quality improvement of irradiated blood components.
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Blood Cells↗
A study of the safety and survival of the adoptive transfer of genetically marked syngeneic lymphocytes in HIV-infected identical twins.
This phase I/II pilot project will evaluate the survival, tolerance, safety, and efficacy of infusions of activated, gene marked, syngeneic T lymphocytes obtained from HIV seronegative identical twins on the functional immune status of HIV infected twin recipients. T cells from each seronegative twin will be obtained by periodic apheresis, separated into CD4 and CD8 enriched populations by monoclonal antibody affinity binding techniques, induced to polyclonal proliferation with anti-CD3 and rIL-2 stimulation, transduced with distinctive neoR retroviral vectors, and expanded 10-1,000 fold in numbers during approximately 2 weeks of culture. These marked T cell fractions will then be infused into the seropositive twins and the survival of the uniquely marked T cell populations will be monitored by vector-specific PCR, while the recipients' functional immune status is monitored by standard in vitro and in vivo testing protocols. A total of 3 cycles of treatment will be given at intervals of 6 weeks between infusions.
Adolescent↗
Treatment of refractory familial hypercholesterolemia by low-density lipoprotein apheresis using an automated dextran sulfate cellulose adsorption system. The Liposorber Study Group.
A subgroup of patients with familial hypercholesterolemia (FH) respond inadequately to standard diet and drug therapy, and are therefore at high risk for the premature development or progression of coronary artery disease. This study evaluated low-density lipoprotein (LDL) cholesterol and lipoprotein (a) removal in a multicenter, controlled trial with a new LDL apheresis procedure (Liposorber LA-15 System). The study comprised patients with FH who had not responded adequately to diet and maximal drug therapy. There were 54 patients with heterozygous FH (45 randomized to treatment and 9 control subjects) and 10 with homozygous FH (all of whom received LDL apheresis). The study included three 6-week treatment phases and a 4-week rebound phase. Treatments were administered at 7- to 14-day intervals. Mean acute reductions in LDL cholesterol were 76% in heterozygous FH patients and 81% in homozygous ones. Time-averaged levels of LDL cholesterol were reduced 41% (243 to 143 mg/dl) in heterozygous FH patients and 53% (447 to 210 mg/dl) in homozygous ones. The substantial acute reduction of lipoprotein (a) (means: 65%, heterozygous FH; 68%, homozygous FH) has not been reported with other therapies. The Liposorber LA-15 System represents an important therapeutic option in FH patients who respond inadequately to diet and drug therapy.
Adult↗
Controlled trial of plasma exchange and leukapheresis in polymyositis and dermatomyositis.
BACKGROUND: The therapeutic options for patients with polymyositis or dermatomyositis that is resistant to corticosteroids are limited, unproved, and often toxic. Uncontrolled trials concluded that both plasma exchange and leukapheresis are beneficial, but despite the considerable use of these approaches, proof of their efficacy is lacking. METHODS: Thirty-nine patients with definite polymyositis or dermatomyositis were randomly assigned to receive plasma exchange (replacement of one volume of plasma with 5 percent albumin in saline), leukapheresis (removal of 5 x 10(9) to 10 x 10(9) lymphocytes), or sham apheresis in a double-blind manner, with 12 treatments given over a one-month period. Muscle strength, functional capacity, and serum levels of muscle-associated enzymes were measured before and after the 12 procedures. RESULTS: In each group 3 of 13 patients had improvements in strength and functional capacity. The condition of 3 patients treated with leukapheresis and 1 treated with plasma exchange deteriorated, and it was unchanged in the other 26 patients. Adverse effects of apheresis included the need for a central venous catheter (9 patients), major vasovagal episodes (3 patients), and severe citrate reactions (2 patients). Despite the occurrence of significant reductions in the serum levels of muscle enzymes with plasma exchange (P less than 0.001) and significant decreases in lymphocyte counts with leukapheresis (P = 0.002), there were no significant differences among the three treatment groups in the final muscle strength or functional capacity of the patients. CONCLUSIONS: As treatments for corticosteroid-resistant polymyositis or dermatomyositis, leukapheresis and plasma exchange are no more effective than sham apheresis.
Activities of Daily Living↗
Syngeneic bone marrow transplantation and adoptive transfer of peripheral blood lymphocytes combined with zidovudine in human immunodeficiency virus (HIV) infection.
OBJECTIVE: To examine the role of syngeneic bone marrow transplantation and peripheral blood lymphocyte infusions combined with zidovudine in the treatment of patients with human immunodeficiency virus (HIV) infection. DESIGN: A partially randomized outpatient trial. SETTING: Outpatient and inpatient facility of the Clinical Center of the National Institutes of Health, a research-based referral facility. PATIENTS: Sixteen patients with HIV infection (15 symptomatic, 1 asymptomatic). INTERVENTIONS: Symptomatic patients were treated with zidovudine, 500 mg orally every 4 hours for 12 weeks, combined with six peripheral blood lymphocyte infusions (four at week 10, two at week 12) and bone marrow transplantation (at week 12) using HIV-seronegative identical twins as donors. After transplantation, patients were randomly assigned to receive either zidovudine, 100 mg every 4 hours, or placebo for 12 months. The asymptomatic patient received zidovudine for the first 12 weeks, discontinuing therapy after transplantation. Immunologic and virologic monitoring were done monthly. MEASUREMENTS AND MAIN RESULTS: Immediately after lymphocyte infusions and bone marrow transplantation, there was an increase in the mean (+/- SE) CD4 cell percent (19.1% +/- 3.1% to 28.1% +/- 3.0%), an increase in the fraction of patients with delayed-type hypersensitivity responses to tetanus toxoid (4 of 13 to 11 of 13) and the development of delayed-type hypersensitivity to keyhole-limpet hemocyanin (a primary immunogen to which only the donor had been immunized) in 8 of 12 patients tested. No significant clinical improvement was noted, however, and there was no overall sustained immunologic improvement. No differences in CD4 cell percents, delayed-hypersensitivity skin tests, HIV cultures, or p24 antigenemia were seen between patients treated with zidovudine or placebo after transplantation. CONCLUSIONS: Although they establish the feasibility of combining zidovudine with cellular immune reconstitution in treating patients with HIV infection, our results show that any benefits from such combination therapy are at best transient. Future attempts at cellular immune reconstitution may need to use improved antiretroviral regimens as well as immunization of donors with HIV-specific antigens.
Adult↗
Utilization patterns of frozen autologous red blood cells. Experience in a referral center and a community hospital.
The risks of homologous blood transfusion have motivated some blood centers and private industry to consider providing long-term storage of frozen, autologous red blood cells as a service. The usefulness of this practice is unknown. We performed a retrospective analysis of frozen autologous red blood cell use in two hospitals. Records were available for 21- and 9-year intervals, respectively. A total of 104 autologous units were cryopreserved for 41 patients. Fifteen (37%) of 41 patients received one or more of their stored units of red blood cells. Twenty-two patients had autologous units frozen in anticipation of elective surgery; 11 (50%) of these 22 patients received some or all of their stored units. Sixteen patients had autologous units stored because of potential transfusion problems related to rare blood types or to the presence of multiple blood cell alloantibodies, and another 3 patients had units frozen simply at their personal request. Only 4 (21%) of these latter 19 patients who donated without a specific planned use eventually received their frozen autologous red blood cells. Long-term autologous frozen red blood cell storage can improve medical management of some patients with anticipated surgical procedures or unusual requirements for transfusion. However, our study suggests that most autologous units frozen without specific planned use will not be transfused.
Blood Preservation↗
Clinical implications of positive tests for antibodies to human immunodeficiency virus type 1 in asymptomatic blood donors.
Of 693,000 volunteer blood donors in Washington, D.C., who were screened for infection with human immunodeficiency virus type 1 (HIV-1) from July 1985 through December 1988, 284 tested positive on both enzyme immunoassay and Western blot assay. To determine the clinical importance of confirmed positive test results in asymptomatic blood donors, we followed 156 donors with positive Western blot assays and 80 donors with positive enzyme immunoassays but negative or indeterminate Western blots at 6-month intervals for a mean of 28 months. As compared with Western blot-negative persons, those with positive Western blots were significantly more likely to be black, male, and first-time donors and to have a history of venereal disease, generalized lymphadenopathy on examination, CD4-cell counts lower than 0.4 x 10(9) per liter, IgG levels higher than 18 g per liter, and antibody to hepatitis B core antigen on initial evaluation. In 17 (11 percent) of the Western blot-positive donors, the disease progressed to Class IV (symptomatic disease), according to the Centers for Disease Control system. CD4 counts below 0.2 x 10(9) per liter, IgA levels above 4 g per liter, abnormal proliferative responses to tetanus toxoid, and positive viral cultures were the strongest predictors of disease progression. Among the 80 donors with repeatedly reactive assay results but either negative or indeterminate Western blot assays, there was no evidence of HIV exposure in their histories, physical examinations, or laboratory evaluations, and manifestations of HIV infection developed in none of them. We conclude that a small number of persons with HIV infection continue to donate blood, despite attempts to exclude them, but that donors who test positive on enzyme immunoassay but persistently negative or indeterminate on Western blot assay probably do not represent a risk for the transmission of HIV.
AIDS-Related Complex↗
Adoptive immunotherapy in the treatment of malignant disease.
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Animals↗
Homozygous familial hypercholesterolemia. Selective removal of low-density lipoproteins by secondary membrane filtration.
Selective plasma filtration with a hollow-fiber membrane device was compared prospectively to plasma exchange in the therapy of a patient with homozygous familial hypercholesterolemia. Four liters of patient plasma was removed biweekly during each of six consecutive plasma exchanges, after which 20 consecutive biweekly 4-liter filtration procedures were conducted. The hollow-fiber membrane retained 94 percent of the low-density lipoprotein (LDL) cholesterol presented to it, and allowed passage of 83 percent of the albumin, 68 percent of the IgG, and 47 percent of the high-density lipoprotein (HDL) cholesterol. Both plasma exchange and plasma filtration decreased the patient's total and LDL cholesterol levels by 80 percent. However, filtration removed significantly less HDL than did exchange (54 versus 71% reduction in HDL levels, respectively); preserved significantly higher levels of IgG, clotting factors, and complement components; and avoided the need for expensive albumin replacement solutions. In addition, the patient tolerated the filtration procedures significantly better than the exchanges. Newer apheresis techniques that selectively deplete plasma of LDL cholesterol, such as secondary membrane filtration, are likely to replace plasma exchange as the therapy of choice in patients with homozygous hypercholesterolemia.
Blood Coagulation Factors↗
Granulocyte transfusion therapy in a child with chronic granulomatous disease and multiple red cell alloantibodies.
A 7-year-old, 17-kg child with chronic granulomatous disease and nocardial pneumonia and osteomyelitis did not respond to antibiotic therapy and developed multiple red cell (RBC) alloantibodies (anti-c, -E, and -Jka). To provide daily granulocyte concentrates, a method was devised to reduce the number of incompatible RBCs per transfusion. Leukapheresis was done with hydroxyethyl starch, and the apheresis product was allowed to sediment by gravity in a plasma expressor for 90 minutes. The leukocyte-rich plasma was separated from the sedimented RBCs by transfer to a satellite bag, and the volume of the product was reduced by centrifugation to approximately 80 ml. RBC content was reduced from 29 +/- 7 to 2.5 +/- 1.0 ml (n = 22, p less than 0.01) and was accompanied by a 70 percent recovery of white cells (range, 49-90%). The final product contained 1.6 +/- 1.0 X 10(10) granulocytes. There were no clinical or laboratory signs of hemolysis during the course of 46 granulocyte transfusions, 37 of which were derived from c-, E-, or Jka-positive donors. The size of most apheresis donor pools is insufficient to provide phenotypically matched granulocyte concentrates daily for patients with RBC alloimmunization. The rapid, simple method described here may allow daily therapy with mismatched concentrates to be administered safely to such patients.
ABO Blood-Group System↗