Platelet and leukocyte transfusions in acute leukemia.
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Biomedical subjects
Publications and source records attributed to J P Hester.
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Cytoreduction of leukemic leukocytosis by continuous flow centrifugation was used in an intermittent or intensive schedule as primary therapy for an average of sixteen months for management of fifteen patients with chronic myelogenous leukemia. The clinical responses and subsequent survival of the patients was studied. Hematologic and chemical changes related to the procedures and the multiple infusions of the sedimenting agent, hydroxyethyl starch, were also studied. This mode of primary therapy offered no survival advantages to patients. There were no adverse effects of the repeated use of the sedimenting agent observed.
Large numbers (2.9 +/- 1.2 X 10(9)) of mononuclear cells can be obtained from incidental samples collected during routine plateletapheresis. We conducted studies comparing characteristics and functions of mononuclear cells derived from venous blood samples and from routine plateletapheresis in the same normal donors. Cell viability was similar in both samples (96 +/- 1% plateletapheresis vs 97 +/- 2% venous blood). Higher concentration of monocytes were observed in the plateletapheresis samples (32.3 +/- 6%) than in the venous blood (14.3 +/- 4%). The procedure of plateletapheresis does not seem to alter lymphocyte or monocyte function. Thus, the functional integrity of these cell populations was demonstrated in terms of natural killer cell activity, blastogenic response to mitogens, local graft-versus-host reactions, monocyte-mediated antibody-dependent cellular cytotoxicity against human red cells, monocyte-mediated tumor cell cytotoxicity, latex phagocytosis, and monocyte-dependent lymphocyte blastogenesis. We conclude that monocytes and lymphocytes obtained during routine plateletapheresis are functionally intact.
In order to determine the minimum dose of buffy coat cells necessary to achieve hematopoietic rescue following supralethal irradiation, mongrel dogs under general anesthesia were subjected to leukacytapheresis using three different techniques of cell separation. The buffy coats were frozen with dimethylsulfoxide and stored at -196 degrees C until transfused. Sixteen dogs were irradiated with 800 rads and were supported with antibiotics and transfusions of irradiated homologous blood. They were transfused with the frozen and thawed buffy coat cells, and, if they survived, they were followed for 100 days, sacrificed, and their tissues studied. The mean yield of mononuclear cells during leukocytapheresis ranged from 4.1 +/- 2.0 X 10(9) (mean +/- SD) to 6.0 +/- 4.0 X 10(9) for the three leukacytapheresis methods; one technique was not as satisfactory as the other two. Six of the 16 dogs fully recovered with evidence of marrow rescue; however, only one had a dose of mononuclear cells less than 11.1 X 10(9). These data indicate that seven to 17 leukacytapheresis procedures would be required to reconstitute a 70 kilogram patient. These preliminary findings suggest that, because the yields of transplantable cells with current technology are not adequate, the transplantation potential of buffy coat cells exposed to mobilizing agents should be evaluated.
Currently, the frequency of granulocyte donation is limited by the prolonged circulation of hydroxyethyl starch (HES). We conducted a Phase I, uncontrolled, multicenter trial to evaluate both the efficacy and safety of a rapidly excreted low-molecular-weight analog of HES (LMW-HES). Seventy-five donors underwent 179 centrifugation leukapheresis procedures using LMW-HES as the red-cell-sedimenting agent. The efficacy of LMW-HES was established by harvesting adequate numbers of leukocytes. Most granulocyte concentrates contained at least 20 X 10(9) neutrophils when 8 l of blood was processed from donors optimally stimulated with steroids. The safety of LMW-HES was documented by the detection of almost no clinically significant adverse effects. In only 1.7 percent of procedures did donors require special attention, and only 1 of 179 procedures (0.6%) was permanently discontinued. Results of laboratory studies were usually normal or their values decreased transiently (approximately 15-25%) as a consequence of plasma volume expansion (dilution). Based on previous experience with HES, LMW-HES and HES perform comparably during leukapheresis. When commercially available, use of this new, rapidly excreted analog should permit more frequent leukapheresis donation.
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The combination of high-dose cyclophosphamide, BCNU, and VP-16-213 followed by autologous marrow rescue was evaluated in the treatment of relapsed leukemia refractory to normal-dose chemotherapy. Cyclophosphamide was given at a total dose of 4.5 g/m2, BCNU at a dose of 300 mg/m2, and VP-16-213 at a dose of 600 mg/m2. Seven high-dose treatments followed by marrow rescue were administered to six patients. Two patients achieved complete remissions, three had partial remissions, and one achieved a minimal response. The toxicity of this regimen was moderate.