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Biomedical subjects

R A Clift

Publications and source records attributed to R A Clift.

At least 109 records · Page 6Linked to original sources
PubMed1985

Cyclosporine as prophylaxis for graft-versus-host disease: a randomized study in patients undergoing marrow transplantation for acute nonlymphoblastic leukemia.

Seventy-five patients, 13 to 49 years of age, with acute nonlymphoblastic leukemia in first remission were treated with cyclophosphamide, fractionated total body irradiation, and marrow transplantation from an HLA-identical sibling and randomized to receive either cyclosporine (CSP) (n = 36) or methotrexate (MTX) (n = 39) as prophylaxis for graft-v-host disease (GVHD). All patients engrafted, and 22 who were given CSP and 21 who were given MTX, are alive at 20 to 47 (median, 35) months (P = .5). Engraftment as assessed by granulocyte recovery (P less than .0005) and platelet transfusion requirement (P = .01) was faster in patients on CSP. Twelve patients (33%) on CSP and 22 (56%) on MTX developed acute GVHD of grades II through IV (P = .07) and 15 of 30 on CSP and 14 of 32 on MTX that were at risk developed chronic GVHD. The most frequent causes of death were interstitial pneumonitis and marrow relapse of leukemia, which occurred with similar frequency in both groups. Beneficial effects observed in patients on CSP included less severe mucositis and shorter duration of hospitalization; adverse effects included renal function impairment and hypertension. These data confirm that CSP is a useful immunosuppressant in patients undergoing marrow transplantation but fail to show a significant improvement in survival as compared with the standard regimen of MTX.

Acute Disease↗
PubMed1985

Marrow transplantation for children in first remission of acute nonlymphoblastic leukemia: an update.

Thirty-eight children between the ages of 0.8 and 17 years with acute nonlymphoblastic leukemia in first remission induced by chemotherapy were given cyclophosphamide, total body irradiation, and bone marrow transplants from HLA-matched donors. Six patients died of pneumonia, one died of metabolic problems, and one died of chronic graft-v-host disease complications. Five patients relapsed between six months and 3.2 years after transplantation. Three of the five died of leukemia, one survives with leukemia three years after transplantation, and one survives in remission off treatment following chemotherapy for 22 months. Twenty-five survive in continuous remission from 1.7 to 8.4 years after transplantation, and the actuarial analysis shows a disease-free survival rate of 64%, with a plateau extending from 3.5 to 8.4 years. All lead normal lives.

Actuarial Analysis↗
PubMed1985

Marrow harvesting for autologous marrow transplantation.

The results and complications of 224 marrow collections from 200 patients with malignant disease who underwent marrow aspiration and storage for subsequent autologous marrow transplantation (AMT) were analyzed. The median age of the patients was 35 years (range 1-68); 131 patients had hematologic malignancies and 69 had solid tumors. Thirty-one patients proceeded directly to AMT after marrow aspiration at a median of 4.5 days (range 0-10). A further 75 patients received AMT a median of 3.0 months (12 days-10 years) after marrow aspiration. The remaining 94 patients had marrow stored but not infused. When a second aspiration was performed from the same patient within seven weeks, the yield of marrow nucleated cells was significantly reduced (p less than 0.02). A negative linear correlation was observed between CFU-C/kg harvested and the day to achieve a posttransplant blood neutrophil count greater than 500/cmm (r = -0.3092, p less than 0.05). A total of 36 (17.4%) complications associated with marrow aspiration were observed including two (0.97%) life-threatening episodes. Postoperative fever accounted for 23 of 34 episodes of minor complications. There was no increased risk of serious complications with decreased time from aspiration to transplant. It was concluded that the morbidity and mortality from autologous marrow aspiration did not differ significantly from that observed in normal donors.

Adolescent↗
PubMed1984

Candidiasis in the transplant patient.

The widely accepted practice of empirically administering amphotericin B to immunocompromised patients with fever unresponsive to antibiotics poses a hazard to transplant recipients receiving immunosuppression with cyclosporine. Improved methods of Candida detection and less toxic antifungals are urgently needed, but in the interim, treatment regimens should require a greater index of suspicion before initiating amphotericin therapy in patients receiving cyclosporine.

Amphotericin B↗
PubMed1984

Marrow transplantation in hepatitis-associated aplastic anemia.

Seventeen patients who developed aplastic anemia in association with viral hepatitis were transplanted with sibling marrow. Of the 16 HLA-identical recipients, 14 were conditioned with cyclophosphamide, 200 mg/kg, and two received 10 Gy total body irradiation. One HLA-nonidentical recipient received 123 mg/kg cyclophosphamide and 10 Gy total body irradiation. Of the 14 patients conditioned with cyclophosphamide alone, one died on day 49 after graft rejection, and 13 had sustained engraftment. Six of the 13 developed acute graft-versus-host disease (GVHD), which led to death from opportunistic infections 84, 97, and 130 days after transplantation in three patients. Four of the 13 developed chronic GVHD, two without preceding acute GVHD. Currently, ten of the 14 cyclophosphamide-conditioned patients are alive 0.9-12.4 (median 5.9) years from transplantation. The two HLA-identical recipients conditioned for grafting with total body irradiation died after failure of engraftment, and one also developed concomitant hepatic venocclusive disease. The mismatched recipient conditioned with radiation and cyclophosphamide died of severe GVHD 18 days posttransplant. We conclude that survival, graft rejection, and incidence of acute and chronic GVHD after marrow transplantation for hepatitis-associated aplastic anemia are similar to those of patients transplanted for aplastic anemia of other etiologies. Previous hepatic damage from viral hepatitis and liver function abnormalities existing at the time of grafting do not appear to increase the risk of posttransplant morbidity and mortality from hepatocellular damage or venocclusive disease in cyclophosphamide-conditioned patients.

Adolescent↗
PubMed1984

Granulocyte collection by continuous-flow centrifugation using arteriovenous shunts.

Two thousand nine hundred twenty-seven granulocyte collections were made using continuous-flow centrifugation with the Aminco Celltrifuge I, the Fenwal Celltrifuge II, and the IBM 2997. There were 231 recipients and 246 donors. In 32 patients attempts to provide daily granulocyte transfusions from a single donor were unsuccessful owing to clotting of the silastic-Teflon arteriovenous shunt. Repeated granulocyte donations produced severe anemia requiring red cell transfusions in all the females and most of the males who had previously donated marrow for transplantation. Granulocyte collections were similar when collected with the Celltrifuge I or the IBM 2997, but collections with the Celltrifuge II were smaller. Infusion of hydroxyethyl starch directly into whole blood as it entered the centrifuge increased granulocyte collections. Granulocyte collections decreased with increasing number of daily collections.

Arteriovenous Shunt, Surgical↗
PubMed1984

Prophylaxis of infection in patients with aplastic anemia receiving allogeneic marrow transplants.

One hundred one patients with severe aplastic anemia underwent allogeneic marrow transplantation and received one of three forms of infection prophylaxis: oral nonabsorbable antibiotics and isolation and decontamination in a laminar airflow room (36 patients); prophylactic granulocyte transfusions from a single family member donor (33 patients); or conventional treatment in single rooms with hand-washing and mask precautions (31 patients). During the period of granulocytopenia, patients in the laminar airflow rooms acquired fewer infections than either of the other groups, but this difference was statistically significant only when compared with the group receiving conventional treatment. Patients in the laminar airflow rooms had significantly fewer infections after engraftment as compared with the other two groups. Incidence of interstitial pneumonia and graft rejection was not different among the three groups. Acute graft-versus-host disease occurred later (Day 47) in the group in the laminar airflow rooms as compared with the group receiving prophylactic granulocyte transfusions (Day 23) or the group receiving conventional treatment (Day 20). The incidence of grades II to IV acute graft-versus-host disease was less in the patients in the laminar airflow rooms but only reached borderline significance (p = 0.08) when compared with the conventionally treated patients. The survival at Day 100 was 92 percent for the group in the laminar airflow rooms, 79 percent for the group receiving prophylactic granulocyte transfusions, and 64 percent for the group receiving conventional treatment.

Adolescent↗
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

Indications for marrow transplantation.

Marrow grafting, originally considered only for end-stage patients after failure of all other treatment, is now the treatment of choice for a variety of malignant and nonmalignant diseases. Donor and recipient selection and the results of marrow transplantation for various diseases and stages of diseases are summarized.

Acute Disease↗
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

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

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

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↗