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

White cell reduction in platelet concentrates and packed red cells by filtration: a multicenter clinical trial. The Trap Study Group.

BACKGROUND: Most previous studies on white cell (WBC) reduction by filtration have been small-scale studies conducted under tightly controlled laboratory conditions. Their results would be the ideal, rather than what might be expected during routine operation. STUDY DESIGN AND METHODS: To obtain information on routine filtration of blood components, data have been collected from a large-scale, ongoing, multicenter clinical trial designed to determine the effectiveness of WBC reduction in or ultraviolet B radiation of platelet concentrates before transfusion in preventing platelet alloimmunization and platelet transfusion refractoriness. The WBC content of blood components both before and after filtration was determined by automated cell counters and a manual propidium iodide-staining method, respectively. Platelet and red cell losses during filtration were measured. RESULTS: The average platelet losses after filtration were 24 +/- 15 percent and 20 +/- 9 percent for apheresis platelets and pooled platelets, respectively. The frequencies at which filtered platelet concentrates contained high levels of residual WBCs (> 5 x 10(6)) were 7 percent and 5 percent for apheresis platelets and pooled platelets, respectively. Further analysis of the platelet filtration data showed that greater numbers of total initial WBCs in the pooled platelets were associated with increased percentages of filtration failure (> 5 x 10(6) residual WBCs). For packed red cells, the average losses during filtration were 23 +/- 4 percent and 15 +/- 3 percent for CPDA-1 units and Adsol units, respectively. The frequencies at which filtered red cells contained > 5 x 10(6) residual WBCs were 2.7 percent for one type of filter and 0.3 percent for another type of filter. CONCLUSION: There were significant losses of platelets during filtration, which could add to the costs of WBC reduction and lead to possible increases in donor exposures. Filtration failures still occurred, despite careful observation of the standard filtration procedures. The number of total WBCs in pooled platelets before filtration has been identified as an important factor in determining the success of WBC reduction.

Comparison of the mutagenicity of quinoline and all monohydroxyquinolines with a series of arene oxide, trans-dihydrodiol, diol epoxide, N-oxide and arene hydrate derivatives of quinoline in the Ames/Salmonella microsome test.

Fourteen new quinoline derivatives were synthesised and their mutagenicity compared in the Ames test using Salmonella typhimurium TA100 as indicator strain with and without (Aroclor-induced) S9 mix. None of the synthesised quinoline derivatives had to our knowledge been examined before in the Ames test. Quinoline and the monohydroxyquinolines were included as reference compounds. Three of the new derivatives, i.e., quinoline 7,8-oxide, N-methyl-quinoline 5,6-oxide and trans-quinoline-5,6,7,8-dioxide appeared to be mutagenic. Quinoline 7,8-oxide was positive only in the presence of S9 mix, the specific mutagenicity amounting to 2498 +/- 96 and 1289 +/- 120 revertants per mumole with 20 and 10% S9 in the mix, respectively. Both N-methyl-quinoline 5,6-oxide and trans-quinoline-5,6,7,8-dioxide were weakly positive, the former only in the presence of the S9 mix, and the latter irrespective of the presence of S9 mix, the specific mutagenicity amounting to 134 +/- 6 and 123 +/- 10 revertants per mumole, respectively. The mutagenic potency of quinoline 7,8-oxide was of the same order as that of quinoline itself and was distinctly lower than that of 8-hydroxyquinoline. Inconclusive results were obtained with trans-7,8-dihydroxy-7,8-dihydroquinoline, 5,6-dihydroxy-7,8-epoxy-5,6,7,8-tetrahydroquinoline and 8-hydroxyquinoline-N-oxide; if these compounds are mutagenic their mutagenic potency would be at least 20-30 times lower than that of the parent compounds. None of the other chemically synthesised quinoline derivatives showed mutagenic activity with TA100 either in the presence or in the absence of S9 mix. The results obtained with the reference compounds were in accordance with literature data.

Biochemical characterization of the neutrophil-specific antigen NB1.

Neutrophil-specific alloantibodies and the antigens they recognize are important in clinical medicine, but little is known about the structure of these antigens. Alloimmunization to the antigen NB1 is a clinically important cause of neonatal neutropenia and febrile transfusion reactions. To study the immunochemistry of the NB1 antigen, we prepared neutrophil plasma membranes and granules by nitrogen cavitation and differential centrifugation and then analyzed them by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting with alloantibodies to several neutrophil-specific antigens. Two different antisera to the neutrophil-specific antigen NB1 identified an approximately 55-Kd protein by immunoblotting on neutrophil membranes from four NB1-positive donors but not on neutrophil membranes from five NB1-negative donors. Four anti-NB1 antisera immunoprecipitated a 58- to 64-Kd protein from extracts of NB1-positive neutrophils surface-labeled with 125I using lactoperoxidase, but not from similarly treated NB1-negative neutrophils. Normal human serum did not immunoprecipitate or immunoblot any proteins from these same neutrophil preparations. The NB1 antigen was detected by immunoblotting in secondary granules but was not found in primary granules. The electrophoretic mobility of the antigen was decreased slightly by reduction, suggesting that intrachain disulfide bonds were present. After reduction, the antigen could no longer be recognized by anti-NB1 antisera, but treatment of the antigen with periodate had no effect on the ability of anti-NB1 antisera to recognize the antigen, suggesting that it is not a carbohydrate. The data suggest that the neutrophil-specific antigen NB1 is present on a 58- to 64-Kd surface glycoprotein that is also present in secondary granules, and that the NB1 epitope is not a carbohydrate but probably resides in the tertiary structure of the protein backbone.

Immunoadsorption of human plasma with protein A-sepharose columns.

Four patients with refractory acute leukemia were treated a total of 31 times with an immunoadsorption system consisting of protein A-sepharose columns, a cell separator, and an elution monitor to test its safety and capacity to remove immunoglobulins. The procedure was tolerated well, and acutely reduced plasma IgG levels by approximately 18 percent. When the procedure was repeated two to three times per week for 3 weeks, IgG levels dropped by 30 to 40 percent, but they gradually returned to pretreatment levels after completion of the course of treatment. Single columns became saturated with IgG after approximately 1500 ml of plasma had passed through the columns. The use of multiple columns sequentially provided continuous extraction of immunoglobulin. One patient regained responsiveness to platelet transfusions after removal of platelet antibodies. These preliminary studies suggest that this immunoadsorption system is effective for specifically removing IgG and that it merits further clinical testing.

Clinical use of indium-111 labeled blood products.

Following the introduction of In-111 oxine as a label for blood cells by McAffee and Thakur in 1976, these procedures have become increasingly important in the practice of nuclear medicine. Of particular interest are studies involving the use of labeled leukocytes for the detection of focal infection. The clinical utility of labeled platelets is less well developed, although the use of platelets to detect the formation of thrombi in blood vessels and on vascular grafts and prostheses is gaining prominence. This report summarizes the techniques presently employed at the University of Minnesota for the labeling of blood products, and their clinical use. Consideration also is given to the desired expertise and cost factors involved in the labeling of leukocytes and platelets.

The relationship of granulocyte ATP to chemotactic response during storage.

During the storage of granulocytes, bactericidal activity declines more slowly than does chemotactic response (CTR). Bacterial killing involves increased activity of the hexose monophosphate shunt, oxygen utilization and the generation of toxic products of oxygen. Chemotaxis is probably a contractile process involving myosin and actin filaments and possibly ATP as a source of energy. Thus, maintainance of ATP may be important in granulocyte preservation. During storage at 1 to 6 C of granulocytes collected by continuous and intermittent flow centrifuge leukapheresis, both CTR and ATP decreased approximately 33 percent. Decreases in CTR and ATP were 12 and 10 percent respectively when cells were stored at 20 to 24 C. Further decreases in CTR and ATP occurred between 24 and 48 hours of storage, although levels of both were higher in cells stored at 20 to 24 C compared with those stored at 1 to 6 C. When the results from all storage conditions were combined, the overall coefficient of correlation between CTR and ATP was 0.71 (p less than .05). Although ATP is probably not the only important variable in granulocyte preservation, granulocytes may resemble red blood cells in that a minimal level of ATP may be necessary for adequate function.

Plasma exchange in the treatment of fulminant idiopathic (autoimmune) thrombocytopenic purpura.

Rapid plasma exchange in a young man with idiopathic (autoimmune) thrombocytopenic purpura and life-threatening haemorrhage acutely increased the platelet-count and enhanced haemostasis. The patient had not responded to steroids, and massive intra-abdominal bleeding had developed after splenectomy, despite numerous platelet transfusions. After plasma exchange, his haemoglobin concentration became normal without further transfusion and his abdominal girth decreased. Therefore emergency reoperation because of intra-abdominal bleeding was no longer required. A cumulative-sums plot of his platelet-count confirmed that plasmapheresis on 2 occasions was followed by a pronounced rise in mean platelet-count. Neither prednisone nor vincristine therapy altered the slope of the plot. The high initial anti-platelet antibody concentration in this patient fell after plasma exchange. These findings indicate that plasmapheresis accelerated clearance of circulating anti-platelet factors in fulminant idiopathic thrombocytopenic purpura.

The effects of transfusion of frozen-thawed deglycerolized red cells on renal graft survival.

In patients that received transplants of cadaver kidneys, prior transfusion improves the prognosis for graft survival. Patients receiving frozen-thawed red cells have better 1-year survival rates than patients given other forms of red cells. The effect of prior transfusions is minimal in patients that recieved transplants of kidneys from living related donors.

Plasma exchange in the treatment of immune disease.

Plasma exchange was investigated as an alternative to the use of toxic drugs to remove unwanted antibody. Studies in rabbits immunized with bovine serum albumin demonstrate that exchange transfusion after a primary immunization results in a rebound of antibody to above preexchange levels. However, exchange transfusion seven, 11, or 18 days after secondary immunization results in permanent lowering of antibody levels. Plasma exchange with the continuous flow centrifuge was used in four patients with hematologic diseases. White cell isoantibodies were removed in a septic leukopenic patient, permitting white cell transfusions. Two patients with immune thrombocytopenia were exchanges; one showed prompt and permanent elevation of platelet count, while the other did not improve. A patient with immune hemolytic anemia had stabilization of hemoglobin levels and decreased Coombs reactivity following plasma exchange.

An adverse pulmonary reaction to cryoprecipitate in a hemophiliac.

An adult with classif Hemophilia A experienced a very severe reaction to transfusion with cryoprecipitate which was manifested as an adverse pulmonary reaction with marked hypoxemia in spite of oxygen therapy. The patient had neither leukoagglutinins nor lymphocytoxic, anti-platelet, or anti-Gm antibodies. His IgA level was normal. The possibility that debris in the cryoprecipitate from leukocytes and platelets contributed to the reaction is discussed.

Granylocyte transfusion: a controlled study in patients with acuute nonlymphocytic leukemia.

Granulocyte transfusions are frequently used during the leukopenic phase of induction chemotherapy for acute nonlymphocytic leukemia (ANLL) although no controlled study has documented their usefulness. We have compared the morbidity and mortality of febrile episodes in granulocytopenic (less than 500/mm3) adults with ANLL who received granulocytes and those who did not. Granulocytes were obtained from related normal donors using a continuous flow centrifuge. Seventeen patients who received 98 transfusions during 23 febrile episodes were compared with 22 patients who received no granulocytes during 35 febrile episodes. No significant difference in clearing of documented infection occurred between the transfused (71%) or the control (76%) group. Granulocytes did not result in more rapid termination of febrile episodes nor in significant decrease in fever 24 hours following the transfusion. Factors contributing to the lack of obvious clincal benefit are discussed.