AIDS and the blood supply.
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Acquired Immunodeficiency Syndrome↗
Biomedical subjects
R A Yankee
Publications and source records attributed to R A Yankee.
Prolonged cryopreservation of human bone marrow.
We tested the viability of human bone marrow stored for 40 to 42 months in the vapor phase of liquid nitrogen. A median of 2 X 10(10) nucleated cells obtained from eight patients were concentrated to 1.3 X 10(10) using discontinuous centrifugation. These were stored in polyolefin bags in volumes of 100 to 500 ml using 10% dimethyl sulfoxide (DMSO) as cryoprotectant. Cell number and granulocyte - monocyte colony - forming cell (CFU-c) plating efficiency were determined before freezing and after thawing, after dilution and removal of DMSO, and after 2 to 4 hr of additional incubation. The median difference in cell number and CFU-c plating efficiency after this prolonged storage was -9 and +2%, respectively. Dilution, washing, and a 2-hr incubation were associated with cell losses of 24, 24, and 19% and increases in CFU-c plating efficiency, ranging from 22 to 79%. The number of viable CFU-c was never significantly lower than the number of CFU-c stored or initially thawed. Vapor phase storage appears to be adequate for prolonged human bone marrow cryopreservation using CFU-c viability as a determinant.
Adult↗
Combination chemotherapy with adriamycin-cyclophosphamide for advanced ovarian carcinoma.
Combination chemotherapy with Adriamycin-cyclophosphamide was employed after surgical treatment in 60 women with Stage III-IV ovarian adenocarcinoma. Of 53 evaluable patients, objective response was noted in 34 of 41 (83%) without prior cytotoxic therapy but in only two of 12 (17%) who had failed a single alkylating agent or radiotherapy (P < .005). Complete response was confirmed by a negative biopsy at the site(s) of prior disease in 12 patients. Eleven of the 12 biopsy-confirmed complete responses were achieved in patients without pretreatment palpable tumor. Twenty-four out of 41 patients with palpable masses responded but only one was confirmed as complete. Confirmed complete responses had a median duration of 24 months, whereas the median duration of all other responses was only seven months. The median survival for patients in whom Adriamycin-cyclophosphamide was the initial chemotherapy was 24 months. The median survival in patients with palpable tumor exceeds that of historical controls matched for age, tumor cell type, and grade (P = .05); the median survival for the confirmed complete responders has not been reached. The toxicity of this regimen was acceptable at doses of Adriamycin and cyclophosphamide of 45 mg and 500 mg/M2 body surface area, respectively. Extensive excision of tumor followed by effective combination chemotherapy offers the best current approach toward improved patient survival in advanced ovarian cancer.
Adenocarcinoma↗
Dilution techniques for optimum recovery of cryopreserved bone marrow cells.
Bone marrow granulocyte progenitor cells (CFU-C) were assayed in methyl-cellulose prior to cryopreservation in Dimethylsulfoxide (DMSO) and after thawing and diluting the DMSO. The time of dilution from 10% to 1% DMSO and the temperature of the sample and diluting media were studied. Compared with samples diluted at 0 degrees-4 degrees C, samples which were diluted at 24 degrees C were more viable by Trypan Blue exclusion (p less than .01) and had greater CFU-C growth in vitro (p less than .01). There was no advantage to prolonging dilution time from 10 minutes at a constant rate to 40 minutes using stepwise technique. Recovery of CFU-C at 24 degrees C ranged from 40% to 114% with a mean +/- S.D. of 67% +/- 19.5%. There was evidence that clonogenic cells were selectively preserved under the conditions described.
Bone Marrow Cells↗
High-dose methotrexate with leucovorin rescue in ovarian cancer: a phase II study.
Methotrexate (MTX) (1--7.6 g/m2) with leucovorin rescue was given to 19 women with stage III-IV ovarian carcinoma after induction of remission with surgical treatment and chemotherapy or after relapse. Adequate hydration with alkalinization prevented nephrotoxicity and no cumulative myelosuppression was observed. Serum MTX levels in nontoxic patients averaged 1 X 10(-6) M 24 hours following a 30-minute iv infusion of MTX at 3 g/m2. Among nontoxic women there was a 50-fold difference in the MTX level which correlated with the mean serum creatinine level. Response was assessed after 6--12 weeks of treatment by laparoscopy in patients with nonpalpable intra-abdominal tumor implants or by physical examination in patients with palpable masses. Despite the high levels of MTX achieved with the weekly schedule, only one partial response occurred among eight patients with visible or palpable metastatic lesions. Progressive disease was observed after 6--12 weeks of treatment in four of eleven women who began to receive MTX without evidence of disease or with lesions of less than 1.5 cm in diameter. MTX at the dose and schedule used in the present study appears to be of no benefit in the treatment of advanced ovarian cancer.
Adult↗
Clinical results of autotransplantation after nitrosourea therapy.
Bone marrow harvested from two previously treated patients was cryopreserved prior to their first dose of Methyl CCNU. The thawed bone marrow was reinfused 96 hours after a subsequent dose of MeCCNU in one patient after the previous dose caused severe myelosuppression. In the other patient, the bone marrow was given 96 hours after an escalation of the MeCCNU dose. In both patients, myelosuppression was abrogated and viable stem cells were recovered in the peripheral blood.
Adenocarcinoma↗
Blood component therapy.
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Acute Disease↗
Electrophoretic mobility distributions of normal human T and B lymphocytes and of peripheral blood lymphoblasts in acute lymphocytic leukemia: effects of neuraminidase and of solvent ionic strength.
Human T and B lymphocytes were found to be distinguishable on the basis of electrophoretic mobility, with the T cells having the higher mobility, in agreement with previous reports. The effects of the enzyme neuraminidase on the electrophoretic mobilities of T and B lymphocytes were determined. T lymphocytes showed a greater decrease in electrophoretic mobility after neuraminidase treatment; the relative mobilities of T and B cells were reversed by neuraminidase treatment, and the electrophoretic distinguishability was enhanced. The electrophoretic mobility distributions of lymphoblasts from patients with acute lymphocytic leukemia were found to differ from those of normal cells in their response to neuraminidase treatment and to changes in solution ionic strength. These results imply that the surface structure of the leukemic cells differs from that of either T or B lymphocytes from normal donors.
B-Lymphocytes↗
Purification and characterization of granulocytic progenitor cells (CFU-C) from human peripheral blood using immunologic surface markers.
The concentration of committed granulocytic progenitor cells (CFU-C) in functionally unique subpopulations of human peripheral blood mononuclear cells has been determined by the in vitro methyl-cellulose assay. Using immunoabsorbent column chromatography and rosette-depletion techniques, we have demonstrated that CFU-C, although not present in either purified T or B lymphocyte populations, are highly concentrated in the "null" cell population, which lacks sheep erythrocyte receptors and surface immunoglobulin. Further fractionation of this null subset has demonstrated that CFU-C do not bear complement receptors, but require the presence of peripheral blood mononuclear cell feeder layers for maximum proliferation.
Bone Marrow Cells↗
Cryopreserved autologous marrow infusion following high dose cancer chemotherapy.
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Agranulocytosis↗
Semicontinuous flow centrifugation for the pheresis of immunocompetent cells and stem cells.
Mononuclear cells from human peripheral blood were purified by semicontinuous flow centrifugation (SCFC) using the Haemonetics model 30 blood cell separator; 64% +/- 7% of the mononuclear cells in 600 ml of peripheral blood were collected in a 30-ml volume. Analysis of sequential 5-ml aliquots of the mononuclear cell concentrate revealed that both immunocompetent cells and granulocytic progenitor cells (CFU-C) were proportional to the cell count throughout the buffy coat. In vitro pheresis of large volumes of human bone marrow resulted in recovery of 63% of the cells, 12% of the hemoglobin, and 84% of the CFU-C in 20% of the original volume. Further centrifugation eliminated 80% of the platelets without loss of cells or CFU-C. SCFC of peripheral blood or bone marrow selectively concentrated mononuclear cells and reduced the contamination by granulocytes and erythrocytes. Large numbers of mononuclear cells can thus be collected for studies in vitro or for cryopreservation and the autologous reconstitution of immunosuppressed or myelosuppressed patients undergoing intensive antitumor therapy.
Antibody-Producing Cells↗
The processing of human bone marrow for cryopreservation and reinfusion.
Bone marrow was aspirated from 22 patients with solid tumors. A median of 1.2 x 10(10) net bone marrow cells were obtained during a 1 hour 45 minute operative procedure. Three methods were used to concentrate the bone marrow for cryopreservation. The greatest concentration of mononuclear cells was obtained by the Haemonetics pheresis procedure. Bone marrow was cryopreserved in 10 % DMSO in volumes ranging from 150 to 700 ml. The thawed marrow was further processed to remove both DMSO and free hemoglobin prior to reinfusion. Cell clumping was observed in the first 6 of the 10 marrows thawed. Acidification of the thawed marrow to pH 6.65 was found to retard cell clumping. The immediate recovery of cells frozen was 66 % with a viability of 50 %. The mean number of viable mononuclear bone marrow cells per kilogram available for reinfusion was therefore 5.5 x 10(7).
Bone Marrow↗
Prophylactic granulocyte support in experimental septicemia.
The purpose of this study was to determine the value of prophylactic granulocyte transfusions in preventing death from sepsis. An intravenous dose of 10(9) Escherichia coli was lethal when given to granulocytopenic rats 6 days following irradiation with 750 rads. Only one of 22 irradiated animals survived the septicemia. Although normal (nonirradiated) animals experienced a transient leukopenia from this dose of organisms, it was less than LD10 for the normal host. There were no deaths in a group of animals receiving irradiation only. A group of 14 irradiated animals was given a single granulocyte transfusion 2 hr before the septic inoculum, and 57% of these animals survived (p less than 0.01). No antibiotic therapy was administered to any of these animals. Irradiated animals who received granulocytes and recovered from sepsis had earlier granulocyte reconstitution than animals irradiated but not given the septic challenge. Platelet reconstitution was the same in both groups. In the rat model, prophylactic granulocyte support of septc animals led to improved survival. It was concluded that granulocyte prophylaxis may be of value in selected patients with transient bone marrow failure who are therefore at high risk from sepsis.
Animals↗
Increase in circulating stem cells following chemotherapy in man.
The number of circulating granulocytic stem cells (CFU-C) was determined by the in vitro methylcellulose technique in cancer patients receiving intermittent chemotherapy. In 17 patients studied prior to therapy, the median CFU-C concentration per 2 X 10(5) mononuclear cells plated was six, compared to a posttreatment median of 23 in 21 patients (p less than 0.001). Large numbers of stem cells were obtained by leukopheresis and cryopreserved with a 99.5% median CFU-C recovery. Cyclical changes in the concentration of stem cells with maximum values of 20 times baseline were demonstrated in a patient studied at weekly intervals during multiple courses of treatment. It was estimated that, at peak CFU-C concentrations, a quantity of stem cells equivalent to that present in a bulk bone marrow harvest could be obtained from the peripheral blood by a 17-liter pheresis. These results suggest that it may be practical to obtain an adequate number of stem cells from the peripheral blood to study autologous stem cell infusion as a means of averting myelosuppression in patients receiving intensive chemotherapy.
Blood Cell Count↗
Use of postpheresis plasma to improve granulocyte yields for transfusion.
Humoral factors which stimulate release of mature granulocytes from body reserves are presumed to be the mechanism through which high yields of granulocytes are obtained from donors by filtration leukopheresis. Postpheresis plasma (PPP) obtained 2 hr after leukopheresis, when infused into normal rats, induced a peak granulocytosis at 3 hr of 22,000/cu mm above controls. A substance in the nylon filters, which caused a peak granulocytosis at 4 hr of 7600/cu mm above controls, was eliminated by washing the filter with 30 volumes of saline. Injection of PPP obtained following leukopheresis with washed filters resulted in an 8000/cu mm increase in granulocytes. One milliliter of PPP given 1 hr before pheresis increased the granulocyte yield from 4.3 to 8.7 times 10-7 granulocytes in a 2-hr run. We conclude that (1) a humoral substance elaborated by the host during filtration leukopheresis induces a granulocytosis in the donor, (2) a substance in commercial leukopaks, which can be eliminated by vigorous washing of the filters, may be responsible in part for granulocytosis observed during leukopheresis, (3) PPP may be used to increase granulocyte yields in donors undergoing leukopheresis.
Animals↗
Correction of poor platelet transfusion responses with leukocyte-poor HL-A-matched platelet concentrates.
Matching donor-recipient pairs for HL-A antigens provides a logical starting point for selecting donors for recipients with extensive prior transfusion histories. However, during the course of continued exposure to even HL-A-matched platelet concentrates, further sensitization occurs, as indicated by progressively poorer post-transfusion increments and transfusion reactions. There is evidence that such sensitization may be due to non-HL-A antigens. Finally, it is postulated that the poor post-transfusion platelet increments obtained when standard platelet concentrates are used result from the leukoagglutinin antigen-antibody reaction involving the platelet as an "innocent bystander." The standard platelet concentrate can be purified by a simple method of centrifugation (178 g times 3 min), removing about 96% of the contaminating white blood cells with concomitant loss of about 21% of the platelets. The use of these leukocyte-poor platelet concentrates can restore compatible transfusion increments in highly alloimmunized thrombocytopenic recipients. The luekocyte-poor concentrates can diminish undesirable transfusion reactions following imcompatible platelet transfusions.
Anemia, Aplastic↗
Complement-dependent and cell-dependent antiplatelet humoral antibody in sera from multi-transfused patients.
Sera from eight multi-transfused patients, who were resistant to platelet trans-fusions from allogeneic donors, were tested for antiplatelet humoral antibody. Complement-dependent cytotoxic humoral antibody against platelets was found in sera from six of eight patients. Cell-dependent cytotoxic humoral antibody against platelets was found in sera from four of seven of these patients. Sera from two patients had cell-dependent antiplatelet activity but no detectable complement-dependent antiplatelet activity. Results of this study argue that both complement-dependent and cell-dependent humoral immunity may be important pathways for in vivo resistance to platelets.
Blood Platelets↗
Prolonged granulocytopenia from incompatible platelet transfusions.
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Adult↗