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Biomedical subjects

C D Buckner

Publications and source records attributed to C D Buckner.

At least 271 records · Page 15Linked to original sources
PubMed1984

Symposium on infectious complications of neoplastic disease (Part II). Granulocyte transfusions.

Laboratory and clinical studies have demonstrated beyond question that granulocyte transfusions can have a beneficial effect on the incidence and course of bacterial infection. The increment of improved survival produced by granulocyte transfusions depends on the effectiveness of the alternative (primarily antibiotic) therapy alone, and this varies with the pattern of bacterial predominance and sensitivity, which is notoriously changeable. The absolute effectiveness of granulocyte transfusion therapy is influenced by the quality of the transfusions and the immune status of both the recipient and the granulocyte donor. The indiscriminate transfusion of inadequate quantities of granulocytes from random donors into sensitized recipients should be discouraged. Severely neutropenic patients with established infection unresponsive to antibiotic therapy are appropriate recipients of granulocyte transfusions. Well-designed programs of prophylactic granulocyte transfusions can reduce the occurrence of bacterial infection in neutropenic patients, but there are few clinical situations in which their use is justified. The use of cytomegalovirus-seropositive granulocyte donors for cytomegalovirus-seronegative recipients should be avoided. There is a need for technical advances that will increase the ease and efficiency of granulocyte procurement.

Animals↗
PubMed1984

Cataracts after total body irradiation and marrow transplantation: a sparing effect of dose fractionation.

We examined 277 patients, who have been followed for 1 to 12 years after marrow transplantation, for cataract development. In preparation for transplantation, 96 patients with aplastic anemia were conditioned with chemotherapy only, usually cyclophosphamide 50 mg/kg X 4 intravenously, while 181 patients (two with aplastic anemia and 179 with a hematologic malignancy) were conditioned with a regimen of total body irradiation (TBI) and chemotherapy. TBI was delivered from two opposing 60Co sources at an exposure rate of 4 to 8 cGy/min, either as a single dose of 10 Gy (105 patients) or in fractions (76 patients), usually at increments of 2 to 2.25 Gy/day for 6 to 7 days for cumulative doses of 12 to 15.75 Gy. To date, 86 patients have developed cataracts. Kaplan-Meier product limit estimates of the incidence of cataracts for patients given chemotherapy only and no TBI, single-dose TBI, and fractionated TBI are 19, 80, and 18%, respectively. On the basis of proportional hazards regression analyses, patients given single-dose TBI had a relative risk of developing cataracts that was 4.7-fold higher than in patients given fractionated TBI or chemotherapy only (p less than 0.00005), suggesting a significant sparing effect with use of TBI dose fractionation. Addition significant risk factors included the chronic use of steroids posttransplant (highly associated with the presence of chronic graft-versus-host disease), and the diagnoses of acute lymphoblastic or chronic myelogenous leukemia.

Adolescent↗
PubMed1984

Allogeneic marrow transplantation in the treatment of preleukemia.

Ten patients with preleukemia and life-threatening pancytopenia were treated with marrow transplantation. In all ten cases allogeneic marrow was successfully engrafted. In three patients prepared for transplantation with cyclophosphamide alone, the abnormal cell clone either persisted or reemerged within 6 months of transplantation. The other seven patients were treated with cyclophosphamide plus total body irradiation before transplantation and six of the seven are alive and well without evidence of disease from 7 to 25 months after transplantation. These results suggest that cyclophosphamide alone before marrow transplantation is incapable of eradicating the abnormal clone. Cyclophosphamide combined with total body irradiation appears more effective, although more time is needed for full evaluation of results. This experience also emphasizes the importance of performing chromosome studies before transplantation for pancytopenic states in order to identify cases of preleukemia.

Adolescent↗
PubMed1984

Long-term survival after marrow transplantation for paroxysmal nocturnal hemoglobinuria with aplastic anemia.

Four patients with paroxysmal nocturnal hemoglobinuria and severe marrow aplasia were given marrow grafts either from allogeneic human-leukocyte-antigen-identical siblings (three patients) or from a syngeneic donor (one patient). The patients with allogeneic grafts were conditioned with regimens that included cyclophosphamide and had sustained and complete marrow engraftment; subsequent tests were negative for paroxysmal nocturnal hemoglobinuria. One patient developed chronic graft-versus-host disease that resolved over 4 years. The patient receiving a syngeneic graft received marrow infusion without preceding immunosuppression. He had prompt engraftment, and hematologic variables returned to normal. A Ham's test done at 3 years was negative, but a complement lysis sensitivity test done 10 years after grafting was positive; the patient, however, remains asymptomatic. All four patients are alive and well 4, 9, 10, and 12 years after transplantation. Paroxysmal nocturnal hemoglobinuria apparently can be treated successfully by allogeneic or syngeneic marrow transplantation without subsequent maintenance therapy.

Adolescent↗
PubMed1984

Bone marrow transplantation or chemotherapy after remission induction for adults with acute nonlymphoblastic leukemia. A prospective comparison.

We compared the outcome of marrow transplantation with that of continued chemotherapy for adults with acute nonlymphoblastic leukemia who achieve a first remission. From May 1977 to July 1982, 111 consecutive adults (ages 17 to 50) with newly diagnosed acute nonlymphoblastic leukemia were treated with induction chemotherapy. Ninety patients (81%) had a complete remission. Forty-four remission patients had available donors: 33 received a transplant and 11 did not. Forty-six patients in remission without matched donors were treated with continued chemotherapy. Kaplan-Meier estimates of 5-year, disease-free survival from complete remission are 49% +/- 18% for the transplant group and 20% +/- 13% for the chemotherapy group. When compared to the chemotherapy group, patients undergoing transplantation had a higher risk of dying during the first 6 months after remission induction but a lower risk of dying thereafter. Within the transplant group, only age influenced survival. Within the chemotherapy group, a leukocyte count of greater than 10 000 mm3 at diagnosis, a French-American-British (FAB) Cooperative Group morphologic status of M-4, M-5, or M-6, and the presence of infection at diagnosis were all associated with shorter survival.

Acute Disease↗
PubMed1984

Therapy of severe aplastic anemia with anti-human thymocyte globulin and androgens: the effect of HLA-haploidentical marrow infusion.

Fifty-four patients with severe aplastic anemia were treated with horse anti-human thymocyte globulin (ATG) and androgens. Thirty of these patients also received an infusion of HLA-haploidentical marrow cells. Only those patients having evidence of hematologic recovery within 3 mo after ATG therapy were considered responders to the immunosuppressive regimen. Of 53 patients evaluable for response, 21 had complete or partial responses and 7 had minimal improvement by defined criteria. The remaining patients did not respond or died. Factors correlated with response to therapy included a short duration of aplasia and a high admission granulocyte count. Thirty-six patients (66.7%) are surviving between 18 and 43 mo, and 18 have died. Deaths were due to hemorrhage and/or infection. Short duration of aplasia and high granulocyte counts also correlated with survival, as did younger age. Four patients with complete or partial responses had a recurrence of severe aplasia 6-17 mo after their first course of ATG. Three of these patients were retreated with ATG (and oxymetholone in two cases). All three had second responses to therapy, but two of the three have had second relapses. The fourth patient responded to oxymetholone alone, but died after a second relapse. Mismatched marrow infusion had no effect on the incidence of response or survival.

Adolescent↗
PubMed1984

Clinical trials with staphylococcal protein A.

Several reports have indicated antitumor effects from the immunoadsorption of plasma from tumor-bearing animals and humans with protein A-containing Staphylococcus aureus. The columns used for these treatments have varied widely in design. In a Phase I trial at the University of Washington, we used protein A chemically linked to crystalline silica for continuous immunoadsorption of plasma in 20 patients with advanced malignancies. Separated blood was perfused continuously over columns containing 50-100 g of immunoadsorbent with 100-200 mg protein A. One calculated plasma volume was perfused over the columns for each treatment. Patients received between 1 and 22 treatments, in total, at one to three treatments per week. Two patients had in vitro treatment of plasma separated from a unit of whole blood obtained by phlebotomy. Side effects were common, were usually manageable, and included chills and fever, nausea, tumor pain, hypotension, and respiratory symptoms. The observed antitumor responses were modest. Three of seven patients with melanoma had indications of responses less than 50%. One of three patients with breast cancer had a response less than 50%. The above studies demonstrate the feasibility of using staphylococcal protein A immunoadsorption in a larger group of patients with a more favorable disease stage.

Drug Evaluation↗
PubMed1984

Oral manifestations of chronic graft-v-host disease.

Sixty patients were studied 180 to 500 days after allogeneic marrow transplantation to determine if late oral abnormalities were associated with the presence of chronic graft-v-host disease (GVHD). Lip and intraoral mucosal surfaces were evaluated for color, keratinization, atrophy, and erythema. Subjective complaints of oral pain and xerostomia were also recorded. Abnormalities were scored on a scale of 0 to 3 and tested for association with GVHD by chi 2 test. Oral manifestations most strongly associated with chronic GVHD included atrophy and erythema or lichenoid lesions of the buccal and labial mucosa and oral pain. Oral manifestations resembled several naturally occurring autoimmune disorders. Recognition of these changes can aid in the clinical diagnosis and assessment of established chronic GVHD.

Adolescent↗
PubMed1984

Marrow harvesting from normal donors.

The experience at a single institution in harvesting marrow for allogeneic transplantation on 1,270 occasions from 1,160 normal donors is presented in detail, together with an analysis of all the donor complications. Four donors were less than 2 years old, and the youngest was 6 1/2 months. No special difficulties were encountered with these young donors. Hospitalization time was three days or less for 99% of the procedures. Six donors had life-threatening complications; three of a cardiopulmonary and two of an infectious nature, and one cerebrovascular embolic episode. Significant operative site morbidity, usually transient neuropathies, occurred in ten procedures. Ten percent of the donations were associated with transient postoperative fever of unknown origin. Increasing donor age was associated with a reduction of the cellularity of the marrow harvest. The use of stored autologous blood permitted the avoidance of blood bank transfusion in 81% of males, 69% of females, and 50% of children. It was concluded that the procedure was associated with a very low risk of complication, but that the involvement of normal donors in such an operation justifies stringent monitoring.

Adolescent↗
PubMed1984

Prophylaxis and treatment of infection of the immunocompromised host by granulocyte transfusions.

Granulocyte transfusions are expensive and involve healthy donors in a procedure which is time-consuming, uncomfortable and not without risk. It is therefore important to consider carefully the circumstances which justify their use. The indiscriminate transfusion of inadequate quantities of granulocytes from random donors into sensitized recipients should be discouraged. Severely neutropenic patients with bacterial infection persisting in the face of maximum antibiotic therapy are clearly appropriate recipients of granulocyte transfusion therapy. Well-designed programmes of prophylactic granulocyte transfusion can reduce the acquisition of bacterial infection in granulocytopenic patients. However, there are very few clinical situations in which their use is justified. A wider use of granulocytes must await better techniques of granulocyte procurement and donor selection.

Agranulocytosis↗
PubMed1983

Graft-versus-host disease and survival in patients with aplastic anemia treated by marrow grafts from HLA-identical siblings. Beneficial effect of a protective environment.

One hundred thirty patients with severe aplastic anemia were conditioned with cyclophosphamide for transplantation of marrow from HLA-identical siblings. The patients were selected for the present analysis according to the criterion of sustained marrow engraftment. Of the 130 patients, 97 are now alive between 1.4 and 11 years (median, 5) after transplantation. Twenty-nine of the thirty-three who died had either acute or chronic graft-versus-host disease (GVHD). Our analysis was directed at identifying factors predicting GVHD and survival after transplantation in patients. Our key findings were that moderately severe to severe acute GVHD had a strong adverse influence on survival; that a protective environment significantly reduced mortality, which corresponded in part to a reduction in and delayed onset of acute GVHD; that refractoriness to random-donor platelet infusions at transplantation adversely influenced survival, particularly among patients with acute GVHD; and that increasing age was associated with increased mortality.

Adult↗
PubMed1983

Prediction by surveillance cultures of bacteremia among neutropenic patients treated in a protective environment.

One hundred seventy-five consecutive marrow transplant patients who were treated in a protective environment for at least two weeks were studied to determine the usefulness of bacteriologic surveillance cultures for the prediction of bacteremia due to Staphylococcus aureus or aerobic gram-negative bacilli. Bacteremia with these organisms occurred in 15 patients (9%), and all patients were colonized with the respective organism before bacteremia occurred. Bacterial colonization was associated with a 17- to 174-fold increase in the relative risk of bacteremia. Negative predictive values were high, but positive predictive values were low owing to the infrequent occurrence of bacteremia. Surveillance cultures also predicted antibiotic sensitivities for all but one organism causing bacteremia. Bacteriologic surveillance cultures in the protective environment are thus useful both for the identification of patients at higher risk of bacteremia with certain types of organisms and for the identification of those who may fail to respond to antibiotic therapy as a result of infection with resistant organisms.

Adolescent↗
PubMed1983

Late effects on gonadal function of cyclophosphamide, total-body irradiation, and marrow transplantation.

One hundred thirty-seven patients had gonadal function evaluated 1-11 years after marrow transplantation. All 15 women less than age 26 and three of nine older than age 26 who were treated with 200 mg/kg cyclophosphamide recovered normal gonadotropin levels and menstruation. Five have had five pregnancies resulting in three live births, one spontaneous abortion, and one elective abortion. Three of 38 women who were prepared with 120 mg/kg cyclophosphamide and 920-1200 rad total-body irradiation had normal gonadotropin levels and menstruation. Two had pregnancies resulting in one spontaneous and one elective abortion. Of 31 men prepared with 200 mg/kg cyclophosphamide, 30 had normal luteinizing hormone levels, 20 had normal follicle-stimulating hormone levels, and 10 of 15 had spermatogenesis. Four have fathered five normal children. Thirty-six of 41 men prepared with 120 mg/kg cyclophosphamide and 920-1750 rad total-body irradiation had normal luteinizing hormone levels, ten had normal follicle-stimulating hormone levels, and 2 of 32 studied had spermatogenesis. One has fathered two normal children. It was concluded that cyclophosphamide does not prevent return of normal gonadal function in younger women and in most men. Total-body irradiation prevents return of normal gonadal function in the majority of patients.

Acute Disease↗