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Biomedical subjects

D Ciavarella

Publications and source records attributed to D Ciavarella.

At least 19 recordsLinked to original sources

Peripheral blood stem cell mobilization by cytokines.

Hematopoietic stem cells circulate in the peripheral blood. These cells can be collected by apheresis techniques either in the unperturbed state, after mobilization following the administration of cytokines like G-CSF or GM-CSF, or during the phase of early blood count recovery following chemotherapy-induced myelosuppression. The number of cells collected following mobilization is greater than that obtained after apheresis in the unperturbed state. There are, however, qualitative differences between unperturbed and mobilized cells. Chemotherapy related mobilization can be potentially dangerous in that severe myelosuppression necessary to achieve mobilization can have serious consequences. There are no controlled studies that evaluate the relative merits of each method of collection. Regardless of the techniques employed peripheral blood stem cells can reliably accelerate hematologic recovery after potentially myeloblative therapy and provide an alternative to bone marrow support.

Blood Cell Count

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

The 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 Kaposi's 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 x 10(9)/l to 120 x 10(9)/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.(ABSTRACT TRUNCATED AT 250 WORDS)

Autoimmune Diseases

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.

Adult

Blood donation and transfusion practices: the 1990 American Association of Blood Banks Institutional Membership Questionnaire.

Responses to the 1990 American Association of Blood Banks (AABB) Institutional Membership Questionnaire were submitted by 2126 regional blood centers, hospital-based blood banks, and transfusion facilities. Data from 2117 of these facilities were considered to be valid. The questionnaire included information on blood donor demographics, number of units collected, and collection procedures; services performed; usage of blood components; and transfusion-transmitted diseases reported during 1989. Institutional members collected 7.4 million whole blood units, of which 90.8 percent were donated for allogeneic use, 6.0 percent were donated for autologous use, and 3.2 percent were donated for directed use. Approximately 630,546 allogeneic and directed-use blood donors were deferred, most often for low hemoglobin or hematocrit values. Approximately 225,205 full allogeneic and directed-donor units were discarded, primarily for elevated alanine aminotransferase levels or the presence of hepatitis B core antibody. The 14.3 million transfused components included 56.7 percent red cell-containing components, 27.4 percent platelets, 11 percent fresh-frozen plasma, and 4.8 percent cryoprecipitate. Institutional members reported 1397 cases of transfusion-associated hepatitis. In this group, 921 patients were tested for hepatitis B surface antigen after the transfusion; 339 (36.8%) were found to be hepatitis B surface antigen positive. The AABB Institutional Questionnaire results provide recent data on blood donor and transfusion-related activities that are vital to the evaluation of current transfusion medicine practices.

Acquired Immunodeficiency Syndrome

The regulation of hematopoietic stem cell collection and storage: the New York State approach.

In December 1988, the New York State (NYS) regulatory code on bone marrow banking went into effect. The goals of the regulations were to codify a high standard of practice, to prohibit charlatanism in the practice or promotion of stem cell banking, and to promote legitimate research. The NYS approach modeled the stem cell regulatory language after that already established for blood banks and clinical laboratories. Also, the stem cell standards are an element of standards applicable to all tissue banks, developed as a result of a comprehensive transplant law enacted in NYS in 1990. The code itself, published as an addendum to this article, mandates that a qualified (by training and experience) medical director and medical advisory committee be appointed, and gives broad and complete responsibility for the services provided to that medical director. Explicit written policies and procedures regarding administrative, technical, safety, and quality issues are necessary, but regulatory micromanagement of the laboratory was avoided by limiting detailed procedural requirements. We believe that these regulations have contributed to the quality and safety of stem cell-related therapies in NYS.

Biological Specimen Banks

Hemopoietic stem cell processing: comparison of progenitor cell recovery using the Cobe 2991 cell washer and the Haemonetics V50 apheresis system.

Using 24 bone marrow (BM) harvests intended for cryopreservation and transplantation, we compared the use of the Cobe 2991 cell washer (2991) and the Haemonetics V50 apheresis system (HV50) for automated BM processing. Our in vitro data indicate that while the mononuclear cell (MNC) concentration of the HV50 product was significantly greater than that of the 2991, the overall MNC recovery of the two products was equivalent. In addition, although the concentration of CFU-GM and BFU-E in the products was equivalent, recovery of these progenitors in the 2991 product was significantly greater than those of the HV50 product. There was no significant difference in either the final product concentration or the overall recovery of cells bearing the primitive myeloid antigens, CD33 or CD34, between the two methods. The HV50 product volume, the red cell and the granulocyte mass were significantly lower than those of the 2991. We conclude that the advantages gained through the use of each machine should be evaluated within the context of the specific intention for the graft. Future advances in the identification and understanding of the primitive stem cell will aid in attempts to evaluate the methods used to isolate these cells.

Adolescent

Hematopoietic stem cell processing and storage.

The techniques to collect, process, and store HSC in anticipation of transplantation are now widely available. Important unresolved issues revolve around the as yet imperfect identification and classification of totipotential progenitors. However, much progress has been and will continue to be made despite this limitation. Research priorities of present and future stem cell processing laboratories should include: 1. Optimization of liquid (nonfrozen) storage techniques. This will permit more complex cell-specific manipulations, such as T-lymphocyte subset selection, isolation of CD34+ populations, treatment in vitro with growth factors, gene transfer experiments, and long-range transport of HSC, to be performed while preserving HSC integrity. 2. A better understanding of the regulation and kinetics of peripheral blood and umbilical cord HSC, to allow optimum collection procedures that do not require marrow harvesting. 3. An intensive study into the optimum conditions of collection, processing, and storage of megakaryocytic progenitors to decrease the long platelet-transfusion dependency of the myeloablated patient. 4. A search for a simple in vitro correlate of engraftment potential of a stem cell preparation. This will greatly improve the quality control functions of the laboratory as well as contribute to better patient selection for transplantation.

Animals

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.

Adolescent

High-dose, potentially myeloablative chemotherapy and autologous bone marrow transplantation for patients with advanced Hodgkin's disease.

Twenty three patients with Hodgkin's disease were treated with BCNU (carmustine), etoposide, and cyclophosphamide at doses of 450-600 mg/m2, 1500-2000 mg/m2, and 120 mg/kg respectively. Bone marrow refrigerated at 4 degrees C for 2-5 days or cryopreserved at -80 degrees C was used to reconstitute bone marrow function. The median age was 28 (range 16-48), and the median Karnofsky performance status was 70. Nineteen patients had progressive disease while on chemotherapy. The median number of prior regimens was three (1-7), and the median number of prior chemotherapy drugs was 10 (range 4-12). Ten patients had received at least two of the drugs used in this study and four had had all three. Indicator lesions included lung (10), peripheral lymph nodes (9), retroperitoneal nodes (8), liver (3), and chest wall masses (2). Ten patients achieved a complete remission (43.5%; 95% confidence limits 23-64%), and five patients had a partial remission (21.7%; 95% confidence limits 5-39%). The median duration of complete remission was 6 months (range 2-13+ months). Responses were shorter in duration for patients with primary refractory disease. Liver function abnormalities were noted in nine (39%) cases. Post transplant, the recovery time was 18 days (range 11-43) for WBC and 24 days (11-77) for platelets. Two patients died of septic episodes while neutropenic. The median number of RBC units used was seven (range 1-45). Ten patients had evidence of pulmonary dysfunction. In seven patients there was symptomatic improvement with steroid therapy, but three patients who were not treated with steroids died as a result of interstitial pneumonia. Future programs should consider bone marrow transplantation in patients with Hodgkin's disease earlier in the course of disease, at the time of minimal residual disease, and employ newer, potentially less toxic drugs.

Adolescent

Treatment of patients with HIV thrombocytopenia and hemolytic uremic syndrome with protein A (Prosorba column) immunoadsorption.

Both antibodies and circulating immune complexes (CIC), which bind to platelets and induce the destruction and clearance of platelets by the reticuloendothelial system, are found in patients with human immunodeficiency virus (HIV) and immune thrombocytopenic purpura (ITP). IgG and CIC were removed from patients' plasma by extracorporeal immunoadsorption using protein A-silica columns (PROSORBA columns). Of the 36 HIV-positive ITP patients treated, 29 received more than one treatment and were evaluated for response. Sixteen patients showed more than a 50% increase in their platelet counts. Platelet-associated IgG (PAIgG) and/or platelet-directed IgG and CIC were elevated in all patients. After four to eight treatments, 16 of 29 patients showed a 170% to 430% increase in platelet counts. A decrease in CIC and PAIgG was noted in responding patients. The median duration of response to date was 8 to 12 months. This treatment was associated with immune modulation and the development of an anti-F (ab')2 antibody response. The antibody functions by complexing with both platelet-binding IgG and CIC, neutralizing their binding capacity for platelets and enhancing their clearance from the circulation. Nine patients with mitomycin-C-induced hemolytic uremic syndrome (HUS) were also treated with PROSORBA columns. Pretreatment platelet counts were markedly reduced while a definite increase in platelet counts was observed upon completion of therapy. There was a decrease of hemolysis and stabilization of renal function in three patients. PROSORBA column treatment has demonstrated marked activity against both HIV-ITP and HUS, and has successfully freed patients from the bleeding diathesis associated with these syndromes.

Acquired Immunodeficiency Syndrome

Acquired toxoplasmic retinochoroiditis after platelet transfusions.

We present a rare well-documented case of acquired toxoplasmic retinochoroiditis transmitted by platelet transfusion. A 52-year-old woman developed severe thrombocytopenia shortly after receiving a sulfamethoxazole-containing antibiotic. This episode was treated with platelet transfusions and a three-day course of corticosteroids. Thirteen days later, she developed an acute febrile illness typical of the typhus-like form of toxoplasmosis. Fifty-six days later, while still taking corticosteroids for recurrent immune thrombocytopenia, she developed an acute macular retinochoroiditis OD. Serology showed recently acquired toxoplasmosis. Epidemiologic investigation revealed no possible source for the toxoplasmosis other than the platelet transfusion.

Adrenal Cortex Hormones

Preparation for blood group-incompatible bone marrow transplantation: comparison of two techniques.

Two similar techniques of red cell depletion of blood group-incompatible marrow prior to bone marrow transplantation were compared in 8 patients. The first method involved a single sedimentation step and removed a mean of 91% of marrow red cells and 33% of marrow nucleated cells. The second method involved multiple sedimentation steps and removed a mean of 96% of red cells and 29% of nucleated cells. Both methods can be recommended to a transfusion service newly involved in a bone marrow transplantation program.

Blood Group Incompatibility

Partial plasma exchange in patients with AIDS and Kaposi's sarcoma. Plasmapheresis in AIDS.

Intensive plasma exchange was performed in seven male homosexual patients with AIDS and Kaposi's sarcoma. Serial 1.2 plasma volume exchange procedures were performed three times a week for six weeks. In five of the patients, plasma replacement included gamma globulin in the form of plasma (two patients), or an IV IgG preparation (three patients). No changes in the mean number of helper-inducer or suppressor-cytotoxic cells were noted during the treatment period or the weeks following completion of the last procedure. The mean mitogenic response of the patients' lymphocytes to PHA increased by 32.4% during the course of the plasmapheresis procedures (p less than .05), but returned to baseline over the eight weeks following treatment. Mitogenic responsiveness to PWM did not significantly increase during the course of treatment. No regression of Kaposi's sarcoma lesions was found in any of the patients treated.

Acquired Immunodeficiency Syndrome