David Ciavarella

Treatment of cancer chemotherapy-associated thrombotic thrombocytopenic purpura/hemolytic uremic syndrome by protein A immunoadsorption of plasma

Background. Chemotherapy‐associated thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (C‐TTP/HUS) is a condition involving thrombocytopenia, microangiopathic hemolytic anemia, and progressive renal dysfunction that develops in 2–10% of patients with a history of malignant neoplasms treated with certain chemotherapeutic agents. Pathogenesis of the disease may depend on the following: (1) generation of endothelial lesions in the kidney microvasculature, resulting from drug toxic effects and/or generation of small soluble circulating immune complexes (CIC), and (2) generation of autoantibodies and/or CIC that trigger aggregation and deposition of platelets around the lesions.

Safety and efficacy of autologous blood donation before elective aortic valve operation

Although the use of preoperative autologous blood donations for patients undergoing elective cardiac operations has increased dramatically in recent years, patients awaiting elective aortic valve replacement have traditionally been denied access to preoperative autologous blood collection programs. We report our experience with 79 patients, each of whom donated 1 to 3 units of autologous blood before an aortic valve operation. All patients had serious aortic valve disease as evidenced by symptoms and preoperative catheterization data. The patients collectively made 129 blood donations. One patient had a syncopal episode within 2 hours of donation and recovered without difficulty. Of the patients who gave autologous blood preoperatively, 68% avoided any homologous blood donor exposure during their subsequent hospitalization for aortic valve replacement. In contrast, in a group of 298 patients who did not give autologous blood preoperatively, only 31% avoided homologous blood exposure during aortic valve replacement (p < 0.0001). Our experience suggests that preoperative autologous blood donation by patients awaiting elective aortic valve replacement is both safe and effective. Patients with aortic valve disease should not be routinely excluded from preoperative blood services.

Marrow storage techniques: a clinical comparison of refrigeration versus cryopreservation.

Fifty-three patients were evaluated for a comparison of the efficacy, safety, and cost efficiency of bone marrow (BM) transplanted after either refrigeration or cryopreservation. Thirty-eight patients had BM stored at 4 degrees C for an average of 3 days and 15 patients had cryopreserved BM stored for an average of 56 days. The average number of cells harvested was 3.8 x 10(8)/kg. The time to WBC recovery greater than 1 x 10(9)/l was 17 days refrigerated and 23 days for cryopreserved BM. The time to platelet recovery greater than 20 x 10(9)/l was 24 days for refrigeration storage and 51 days for cryopreserved BM. Four of 38 patients with refrigerated vs. 4/15 patients with cryopreserved BM experienced delayed engraftment (p less than 0.05). Refrigeration storage requires no special equipment, is cheaper than and presents a safe and viable alternative to cryopreserved BM in reconstituting hemopoiesis following high-dose chemo-radiotherapy.

The use of protein A columns in the treatment of cancer and allied diseases

SummaryThe staphylococcal cell-wall protein known as protein A has been explored as a therapeutic modality in the treatment of cancer and allied diseases. Protein A binds the Fc fragment of IgG 1,2 and 4, and preferentially binds to IgG incorporated into immune complexes. Early investigators focused on the immune-suppressive effects of immune complexes in cancer and, based on in vitro experiments, postulated that clearance of immune complexes in vivo would permit effective immune clearance of cancer cells. A large clinical trial of the perfusion of cancer patient plasma over protein A was subsequently undertaken. Results were generally disappointing, with no complete remissions and overall response rates of 22%. Response rates for Kaposis sarcoma (39%) and breast adenocarcinoma (26%) were somewhat encouraging, and further clinical trials in these disorders are ongoing. More impressive have been the responses to protein A perfusion in immune thrombocytopenia and hemolytic-uremic syndrome. Using a protein A-silica device, Snyder et al. reported responses in 42% of immune thrombocytopenia patients, with mean increases in platelet count from 27×109/l to 120×109/l. On the basis of these results, the protein A-silica column was approved by the United States Food and Drug Administration for treatment of immune thrombocytopenia. Equally encouraging are reports of an overall 59% response rate in cancer chemotherapy-related hemolytic-uremic syndrome. Reported toxicities include fever, chills, hypotension, dyspnea and musculoskeletal pain. With rare exceptions, these reactions are easily treated and do not result in cessation of therapy. Unfortunately, the mechanism of action of plasma perfusion over protein A is very unclear. The best available evidence would point to an immunomodulatory role, manifested by stimulation of an anti-idiotype response in immune thrombocytopenia. A better understanding of how protein A immunoadsorption alters the immune response will be necessary to permit optimum use of this therapy.

Should hospitals collect blood components? Yes: Hospitals put patients first

Stand-alone blood collection centers throughout the world have suffered in recent years from cost overruns, quality and regulatory problems of major proportion, and a subsequent deterioration of service levels to their communities. Their leaders have been probed by public interest groups, the media and governmental bodies, removed from positions of authority, and sadly, subpoenaed, vilified in public and even jailed. Patients, healthcare providers and hospitals have suffered through this period as well, and continue to search for alternatives to their largely monopoly suppliers. In most cases, the best alternative is the one they control themselves. Should hospitals collect blood components? Yes, since their mission--patient care--takes precedence over that of any non-provider healthcare organization. Patients and the public-at-large gain many things by the continued presence of hospitals in the provision of donor services: provider and patient needs are given first billing, and innovation in blood services is encouraged by the transfusion medicine physicians and allied health professionals who are closest to the patient. Service requirements are recognized and met faster and in simpler ways, and quality concerns are addressed with a minimum of bureaucracy and a maximum of common sense. Finally, when hospitals control their own donor programs, costs are more easily tracked and better controlled.