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Biomedical subjects

C D Buckner

Publications and source records attributed to C D Buckner.

At least 253 records · Page 14Linked to original sources
PubMed1985

Treatment of acute graft-versus-host disease after allogeneic marrow transplantation. Randomized study comparing corticosteroids and cyclosporine.

Seventy-seven patients (age 12 to 46 years) who underwent allogeneic marrow transplantation for hematologic malignancy or aplastic anemia and who had grade II to IV acute graft-versus-host disease despite methotrexate prophylaxis were randomly assigned to receive methylprednisolone 2 mg/kg per day intravenously (n = 39) or cyclosporine (n = 38) either 12 to 15 mg/kg per day orally or 3 to 5 mg/kg per day intravenously. In both groups, clinical and histologic evidence of graft-versus-host disease was detected at medians of 16 and 25 days, respectively. Drugs were given for a minimum of 14 days unless significant deterioration occurred. If graft-versus-host disease did not improve with this therapy, treatment with a second agent was initiated. Treatment responses were scored after reviewing clinical and laboratory data collected before, during, and after the 14-day treatment period. Possible scores were as follows: -1, worse; 0, no change; + 1, improvement in one organ system (skin, liver, gut) with no deterioration in the other two; +2, complete resolution of all involved systems. The median response score among 39 methylprednisolone-treated patients was 0. Sixteen patients (41 percent) showed response to treatment, 11 with partial and five with complete response. The median response score among 38 cyclosporine-treated patients was +1. Twenty-three patients (61 percent) showed response to treatment, 15 with partial and eight with complete response (p = 0.039). Twenty patients receiving methylprednisolone and 18 receiving cyclosporine required additional therapy. The incidence of chronic graft-versus-host disease was similar in both groups. It developed in all nonresponding patients at risk who had received secondary therapy. Among responding patients (scores +1 or +2) who were not given additional treatment, chronic graft-versus-host disease developed in eight of 11 (72 percent) receiving methylprednisolone and five of ten (50 percent) receiving cyclosporine. Survival beyond 17 months was similar in the two groups (28 percent and 24 percent, respectively). These data suggest that cyclosporine is a useful agent for the treatment of acute graft-versus-host disease, comparable in its efficacy to methylprednisolone.

Acute Disease↗
PubMed1985

Marrow transplantation for leukemia following fractionated total body irradiation. A comparative trial of methotrexate and cyclosporine.

Fifty-six patients, 30-47 yr of age, with leukemia in relapse received allogeneic marrow transplants from HLA-identical siblings. All patients were treated with cyclophosphamide (120 mg/kg) and 7 daily fractions of 2.25 Gy of total body irradiation (TBI) for seven consecutive days. Nine patients (16%) are currently alive and free of disease 324-845 days from transplantation. The actuarial relapse and survival rates at 2 yr were 56% and 9.5% respectively. These data were not remarkably different from those in previous studies using 10 Gy of TBI administered as a single dose. Thirty patients were randomized to receive methotrexate (MTX) and 26 to receive cyclosporine (CSP) as postgrafting prophylaxis for acute graft-versus-host disease (GVHD). The probability of developing significant acute GVHD by day 100 post-transplant was 71% for patients in the MTX group and 45% for patients in the CSP group (p less than 0.05). The probability of relapse was 37% for patients in the MTX group and 70% for patients in the CSP group (p less than 0.05). Transplant-related deaths were more frequent in the MTX group and leukemic deaths were more frequent in the CSP group although this may have been related to an uneven distribution of high-risk patients. Long-term disease-free survival was comparable. Patients in the MTX group had more severe mucositis, more alveolar pneumonias and possibly more deaths due to complications of acute and chronic GVHD. Patients in the CSP group had a higher incidence of hypertension, neurological complications and renal dysfunction.

Adult↗
PubMed1985

Design and use of double lumen right atrial catheters in bone marrow transplant recipients.

Bone marrow transplant recipients require central venous catheterization for a variety of fluids. They are also particularly susceptible to infection. Here we discuss the use of double lumen catheters to reduce the number of invasions necessary. We make particular reference to infection, neutropenia, prophylactic antibiotics, additional catheters, and presence of graft vs host disease.

Adolescent↗
PubMed1985

Whole blood immunoadsorption of anti-A or anti-B antibodies.

Immunoadsorption columns capable of specifically removing antibodies show promise as an alternative treatment to plasma exchange. Most columns are designed to be perfused with plasma and it is necessary to use a plasma separation device (filtration or centrifugation) for the procedure. This increases the cost and complexity of the immunoadsorption procedure. We have adapted immunoadsorption columns capable of removing anti-A or anti-B red cell antibody from plasma to a whole blood perfusion system by coating the silica with a thin layer of collodion and incubating with albumin (1%). Patients were given heparin, 25 units/kg intravenously, followed by a continuous infusion of 3% citrate and heparin, 10 units/ml, to achieve a ratio of 1:16-1:20 (anticoagulant to whole blood) before delivery through the columns. Effective and specific removal of anti-A or anti-B antibody was achieved with this technique. Effects on coagulation parameters and the complement system were acceptably small.

ABO Blood-Group System↗
PubMed1985

Allogeneic marrow transplantation in the treatment of MOPP-resistant Hodgkin's disease.

Eight patients with disseminated Hodgkin's disease resistant to MOPP (mechlorethamine, vincristine, procarbazine, and prednisone) chemotherapy were treated with high-dose chemoradiotherapy and marrow transplantation from an HLA-identical sibling. Two patients remain alive in unmaintained complete remission (CR) at 38 and 39 months after transplant. In the other six patients, reasons for failure included relapse of lymphoma (two patients), or death due to complications of the transplant procedure, including Legionnaire's disease, disseminated zoster, graft-v-host disease, and aspiration pneumonia secondary to severe mucositis. These results demonstrate that some patients with MOPP-resistant Hodgkin's disease can obtain prolonged CR following intensive chemoradiotherapy and allogeneic marrow transplantation.

Adult↗
PubMed1985

Marrow transplantation for chronic myelocytic leukemia: a controlled trial of cyclosporine versus methotrexate for prophylaxis of graft-versus-host disease.

Forty-eight patients with chronic myelocytic leukemia, aged 11 to 47, were treated with high-dose cyclophosphamide and fractionated total body irradiation, followed by infusion of marrow from HLA-identical siblings. They were randomized to receive either methotrexate (MTX) (n = 23) or cyclosporine (CSP) (n = 25) as postgrafting prophylaxis for graft-v-host disease (GVHD). All patients had evidence of sustained hematopoietic engraftment. Seventeen of the 25 patients receiving CSP and 17 of the 23 patients receiving MTX are alive between one and almost four (median, 1.7) years, with an actuarial survival rate at three years of 62% and 66%, respectively (P = .60). Also, with respect to most other parameters studied, the two drugs were identical. The probability of acute GVHD was .42 and .46, respectively (P = .70), that of chronic GVHD, .50 and .63 (P = .44), and that of death from transplant-related causes, .30 and .24 (P = .51). There were no differences in the speed of granulocyte and platelet engraftment (P = .82 and .94, respectively), and the duration of hospitalization was comparable (P = .58). Patients receiving MTX required red cell transfusions for a shorter period of time (P = .02), but had a slightly increased morbidity from early oral mucositis. The leukemia recurrence rates were comparable (P = .60). With the regimens used in this study, we conclude that CSP failed to reduce the incidence of GVHD and improve the survival of patients with chronic myelocytic leukemia when compared to results with standard MTX.

Adolescent↗
PubMed1985

A randomized trial of antihuman thymocyte globulin versus murine monoclonal antihuman T-cell antibodies as immunosuppressive therapy for aplastic anemia.

A prospective randomized trial was undertaken to compare the efficacy and toxicity of murine antihunman T-cell monoclonal antibody (mcAb) therapy to that of horse antihuman thymocyte globulin (ATG) in the treatment of severe aplastic anemia (AA). Patients were randomized into one of the two treatment groups as well as to receive or not receive androgens. Median duration of aplasia prior to treatment was 1.5 and 2.2 months for the mcAb and ATG groups, respectively. One of 12 patients who received mcAb therapy had a partial response, whereas four of 13 patients receiving ATG had a complete or partial response. Of the 11 patients who failed mcAb treatment, six were subsequently treated with ATG and two improved. Ten of 13 patients who received ATG are surviving compared with seven of 12 patients who received mcAb. Toxicity of mcAb therapy was less than that of ATG. Future studies are needed to determine whether mcAbs known to be immunosuppressive are of benefit as therapy for patients with AA.

Adolescent↗
PubMed1985

Autologous marrow transplantation in patients with acute nonlymphocytic leukemia in first remission.

Thirteen patients with acute nonlymphocytic leukemia underwent autologous bone marrow transplantation (ABMT) following high doses of cyclophosphamide and total body irradiation while in first complete remission. After marrow infusion four patients received human leukocyte interferon and nine received intravenous methotrexate. One patient died on day 16 of septicemia associated with severe gastrointestinal toxicity. In the remaining 12 patients the median day of achieving a circulating granulocyte level of 500/mm3 was 29 (range 15-94 days). Eight of 12 evaluable patients achieved a sustained platelet count of 20,000/mm3 or greater in a median of 44 days (range 12-116 days) and four patients did not achieve this level before death on days 116-396. One patient died on day 116 of interstitial pneumonitis secondary to cytomegalovirus. Eight patients relapsed 58-365 days after AMBT (median 335 days), and all have died. Three patients are alive and well without relapse 26-50 months after ABMT. This study demonstrated that poor engraftment was a frequent complication of ABMT when early posttransplant cytotoxic therapy was attempted. Relapse of leukemia and the number of long-term survivors in this small group of patients was not different from that expected following conventional therapy.

Acute Disease↗
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

Effects of in vitro depletion of T cells in HLA-identical allogeneic marrow grafts.

We report results of a pilot study designed to evaluate the effects of in vitro depletion of T lymphocytes from donor marrow in patients receiving HLA-identical marrow grafts for treatment of hematologic malignancies. Twenty patients aged 31 to 50 years were prepared for transplantation with cyclophosphamide (120 mg/kg) and fractionated total body irradiation (12.0 or 15.75 Gy). All received cyclosporine after grafting. The donor marrows were treated with a mixture of eight murine monoclonal antibodies and rabbit serum complement in a manner that achieved a 2- to 3-log depletion of T cells in most patients. Initial engraftment occurred promptly in 19 of the patients, and only three had clinically significant acute graft-versus-host disease. Depletion of donor T cells, however, was associated with an increased incidence of graft failure, which occurred as late as 244 days after transplantation. Graft failure was transient in one patient but apparently was irreversible in seven others. Three of the seven patients had cytogenetic but not morphological evidence of leukemic relapse at the time of graft failure. All seven patients with irreversible graft failure have died, six after receiving second bone marrow transplants. Seven of the eight cases of graft failure occurred among the 11 patients prepared for transplantation with 12.0 Gy of total-body irradiation, and only one occurred among the nine patients with advanced malignancies who received 15.75 Gy of total-body irradiation. This association with irradiation dose suggests that host factors were partly responsible for the graft failures. Because graft failure seldom occurs in irradiated recipients of unmodified HLA-identical allogeneic marrow transplants, it appears that T cells in the donor marrow may serve a beneficial function in helping to maintain sustained engraftment possibly by eliminating host cells that can cause graft failure. Optimal application of in vitro manipulation of donor marrow as a method for preventing graft-versus-host disease will require more effective immunosuppression of the recipient in order to assure sustained engraftment and function of donor stem cells.

Adult↗
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↗
PubMed1985

Marrow transplantation for treatment of pregnancy-associated aplastic anemia.

This report describes the results of marrow transplantation in four patients with aplastic anemia during the last trimester of their pregnancies. All patients were treated with supportive care until delivery. Because of persistent severe aplasia, marrow transplantation was then performed 1.6-11.0 months postpartum. Marrow donors were HLA-identical siblings. Although all were at increased risk for graft rejection because of their pregnancies as well as their long transfusion histories, two patients were successfully engrafted and now survive 12 and 95 months after transplant. The other two patients rejected their grafts despite attempts at second or third marrow infusions. Both died of infectious complications, 42 and 111 days after transplant.

Adult↗
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↗