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Biomedical subjects

C D Buckner

Publications and source records attributed to C D Buckner.

At least 217 records · Page 12Linked to original sources
PubMed1987

Infectious complications in patients undergoing marrow transplantation: a prospective randomized study of the additional effect of decontamination and laminar air flow isolation among patients receiving prophylactic systemic antibiotics.

99 patients with hematological malignancies underwent allogeneic marrow transplantation from HLA-identical sibling donors and were randomized to receive one of two forms of infection prophylaxis while granulocytopenic: (1) prophylactic systemic antibiotics in a conventional hospital room (PSA, 50 patients) or (2) decontamination, isolation in a laminar air flow room and the administration of prophylactic systemic antibiotics (LAF + PSA, 49 patients). Only 1 patient (3%) in the LAF + PSA group acquired septicemia while granulocytopenic compared to 11 (24%) patients in the PSA group (p less than 0.005). Three patients (6%) in the LAF + PSA group acquired major localized infections compared to 9 (18%) in the PSA group (p = 0.06). There was no significant difference in days in hospital post transplant, days of granulocytopenia, days of fever, incidence of acute graft-versus-host disease, interstitial pneumonitis or overall survival. We conclude that the use of prophylactic systemic antibiotics added to decontamination and laminar air flow isolation of patients undergoing marrow transplantation significantly reduces the incidence of septicemia in the granulocytopenic period.

Adolescent↗
PubMed1987

The effect of prophylactic intravenous immune globulin on the incidence of septicemia in marrow transplant recipients.

Ninety-seven patients randomized to receive (45 patients) or not to receive (52 patients) intravenous cytomegalovirus immune globulin before and after allogeneic marrow transplantation were evaluated retrospectively for the occurrence of bacterial and fungal septicemia in the first 100 days post-transplant. In a proportional hazards regression test, infection prevention regimens, immunoglobulin administration, age and occurrence of acute graft-versus-host disease were tested simultaneously for the occurrence of septicemia in the pre- and post-engraftment period. Of these factors, only patients receiving immunoglobulin had significantly fewer episodes of septicemia following engraftment with 11 (26%) patients in the globulin group having 14 episodes compared to 22 (42%) patients in the control group having 27 episodes (p = 0.039). None of the patients experienced complications with the immunoglobulin infusions. These results suggest that the administration of intravenous immunoglobulin may be a practical and effective method to decrease the incidence of septicemia following marrow transplantation.

Bone Marrow Transplantation↗
PubMed1987

Venocclusive disease of the liver after chemoradiotherapy and autologous bone marrow transplantation.

We determined the incidence of venocclusive disease of the liver (VOD) in 96 recipients of autologous bone marrow transplants (BMT) to be 9.4%, a figure less than that reported for allogeneic transplantation. The development of VOD was compared in a cohort of 21 autologous BMT recipients and in 56 randomly chosen, comparably conditioned, concurrent allogeneic BMT recipients. One of these 21 (4.8%) autologous recipients developed VOD, versus 14 of 56 (25%) allogeneic recipients (P less than 0.05). Logistic regression analysis confirmed pretransplant hepatocellular dysfunction as a risk factor for VOD, and suggested that the use of methotrexate and/or cyclosporine contributes to the development of VOD after chemoradiation therapy. However, a graft-versus-host reaction cannot be excluded as a cause of the higher incidence of VOD in allogeneic recipients.

Adolescent↗
PubMed1987

Second marrow transplants in patients with aplastic anemia rejecting the first graft: use of a conditioning regimen including cyclophosphamide and antithymocyte globulin.

Sixteen (11%) of 146 consecutive patients with severe aplastic anemia prepared for engraftment with cyclophosphamide (200 mg/kg) rejected marrow grafts from their HLA-identical siblings. They were given a second marrow transplant from either the same (n = 13) or a second (n = 3) HLA-identical sibling between 23 and 743 (median 86) days after the first transplant. The preparation for the second transplant included cyclophosphamide, 50 mg/kg, on each of four successive days. Twelve hours after each of the first three doses of cyclophosphamide, antithymocyte globulin, 30 mg/kg/dose, was infused. One of the 16 patients died from infection too early after the second transplant to be evaluated, two had failure of engraftment and died with infection, one rejected the second graft and is surviving almost 5 years later with full autologous marrow recovery, and 12 had successful and sustained second grafts. Of these 12, six are surviving between 11 months and 7 3/4 years. Four of the six have no graft-v-host disease (GVHD), while two have chronic GVHD requiring treatment. Five have Karnofsky scores of 100% and one of 90%. Six of the 12 patients with sustained grafts died between 63 days and 38 months after transplantation, four with infections (related in two patients to chronic GVHD), one with acute GVHD, and one with hemorrhage. The average interval from first to second transplant was 308 days during the past five years, compared to 61 days in earlier patients. Five of seven recent patients are surviving, compared to two of nine earlier patients. In conclusion, successful second transplants after cyclophosphamide and antithymocyte globulin are possible in most patients with aplastic anemia who have rejected their first marrow grafts; however, mortality remains high, with only 40% of the patients becoming long-term survivors.

Adolescent↗
PubMed1987

Marrow transplantation for children with acute lymphoblastic leukemia in second remission.

Fifty-seven children between the ages of 3 and 17 years with acute lymphoblastic leukemia (ALL) in chemotherapy-induced second bone marrow remission were given cyclophosphamide, total body irradiation, and bone marrow transplants from HLA-matched donors. Sixteen died of transplant-related complications. Eighteen relapsed between 56 and 833 days after transplantation, and 16 died of leukemia. Two survive in remission off treatment following chemotherapy. Twenty-three survive in continuous remission from 1.4 to 10.4 years after transplantation and the actuarial analysis shows disease-free survival of 40% with a plateau extending from 2.5 to 10.4 years.

Acute Disease↗
PubMed1987

Graft-versus-leukemia in man: relationship of acute and chronic graft-versus-host disease to relapse of acute leukemia following allogeneic bone marrow transplantation.

To study the effect of acute and chronic graft-versus-host disease (GVHD) on recurrent leukemia, we analysed data on patients with acute leukemia receiving allogeneic marrow transplants in Seattle between 1970 and 1986. Four hundred fifty-four patients survived in remission 150 days after HLA-identical transplant and 114 currently survive five to fifteen years after marrow grafting. At the time of transplant, 252 patients had acute nonlymphocytic leukemia in remission or relapse and 202 had acute lymphocytic leukemia in remission or relapse. According to Kaplan-Meier estimates, recurrence of leukemia following transplantation was observed in 28% of patients developing moderate to severe (grade II-IV) acute GVHD and 48% of patients with no or mild (grade O-I) acute GVHD (p = 0.0028). Relapse was observed in 34% of patients developing clinical extensive chronic GVHD and 45% of patients free of chronic GVHD (p = 0.0001). The incidence of recurrent leukemia was 28% in recipients developing both acute and chronic GVHD and 52% in patients free of both acute and chronic GVHD (p = 0.0001). These data confirm an apparent graft-versus-leukemia effect in patients developing GVHD after allogeneic marrow grafting. Current studies are aimed at determining the influence of such apparent adoptive immunotherapy within the different categories of leukemia and methods to manipulate and augment the clinical benefit of this observation.

Acute Disease↗
PubMed1987

Graft versus leukemia effect in man: the relapse rate of acute leukemia is lower after allogeneic than after syngeneic marrow transplantation.

To determine whether allogeneic bone marrow transplantation (BMT) is associated with a graft vs leukemia (GVL) effect in man, the relapse rate of acute leukemia after allogeneic BMT was compared with that occurring after syngeneic (genetically identical twin) BMT. The patients had ALL or ANL in second or subsequent complete remission (CR) or in relapse. The allogeneic and syngeneic marrow recipients were comparable in diagnosis, age, and interval from diagnosis to BMT and received comparable chemoradiotherapy regimens. Allogeneic marrow recipients, however, received, in addition, GVH disease prophylaxis, most often methotrexate and, more recently, cyclosporine or both. All patients treated by the Seattle team from 1970-1986 are included. Leukemic recurrence was observed in 62% of 785 allogeneic recipients and 75% of 53 syngeneic recipients (p less than 0.0001). The results confirm the circumstantial evidence for a GVL effect exerted by allogeneic marrow. Analyses are in progress to determine whether a GVL effect exists in subsets of patients as a function of their particular diagnosis or status at the time of BMT.

Bone Marrow Transplantation↗
PubMed1987

Allogeneic and syngeneic marrow transplantation following high dose dimethylbusulfan, cyclophosphamide and total body irradiation.

Fifty-eight patients received an allogeneic or syngeneic marrow transplant following conditioning with high doses of dimethylbusulfan (DMB), cyclophosphamide (CY) and total body irradiation (TBI). Thirty-two patients had either chronic myeloid leukemia (CML) in accelerated phase or blast transformation, or acute leukemia after first relapse. The actuarial survival of these 32 patients at 3 years was 12% compared with 25% for a group of 206 patients with similar diagnoses prepared for transplantation with CY and TBI alone. This reduced survival was associated with a greater incidence of early non-leukemic deaths, in particular as a result of severe hepatic veno-occlusive disease. The incidence of leukemic relapse was not different in the two groups. Of 13 patients with CML in chronic phase who received syngeneic transplants following DMB, CY and TBI, nine are alive in hematologic and cytogenetic remission from 3.9 to 9.4 (median 6.2) years post-transplant.

Adolescent↗
PubMed1987

Experience with marrow harvesting from donors less than two years of age.

Experience in harvesting marrow for allogeneic marrow transplantation from 23 infant donors is presented. Ten donors were less than one year of age and 13 were between one and two years of age at the time of initial donation. None of these donors experienced major difficulties following the aspiration procedure. Three donors had significant medical problems diagnosed during the pre-donation evaluation. All aspirations were performed from iliac crests and all donors were given general anesthesia. Irradiated blood bank transfusions were given to 85% of the donors during the procedure. The volume of marrow obtained ranged from 11.5 to 19.3 ml/kg donor weight and contained from 2.5 to 10.4 x 10(8) nucleated cells/kg donor weight. Thus, very young children may safely donate marrow for allogeneic transplantation and the nucleated cell count obtained is substantial.

Age Factors↗
PubMed1987

The treatment of acute non-lymphoblastic leukemia by allogeneic marrow transplantation.

The results are presented of allogeneic transplantation for 363 patients with acute non-lymphoblastic leukemia treated in Seattle from May 1973 through December 1985. The probabilities of surviving disease-free for 5 years for patients transplanted in first remission, in second remission, in untreated first relapse or in chemotherapy-resistant first relapse were 46%, 28%, 30%, and 21%, respectively. The corresponding probabilities of relapse within 5 years were 25%, 37%, 36% and 56%, respectively. Prognostic factors predictive of survival after marrow transplantation for patients transplanted in first remission included age, donor sex and the number of circulating blasts at the time of diagnosis. Acute graft-versus-host disease (GVHD) had a major adverse effect on survival, but chronic GVHD decreased the risk of relapse for patients transplanted in first remission.

Bone Marrow Transplantation↗
PubMed1987

Marrow transplantation for patients with acute lymphoblastic leukemia in first marrow remission.

Forty-six patients with acute lymphoblastic leukemia (ALL) in first marrow remission underwent allogeneic marrow transplantation between August 1976 and June 1985. Thirty-four patients had no extramedullary disease after remission induction and 12 had extramedullary relapses prior to or at the time of marrow grafting. The conditioning regimen included cyclophosphamide followed by total body irradiation, 9.2-15.75 Gy, administered as a single dose or in six or seven daily fractions. Marrow donors were genotypically HLA-identical siblings. Methotrexate was given as prophylaxis for graft-versus-host disease (GVHD). Forty-four patients had marrow engraftment. The incidence of grades II-IV acute GVHD was 52%. Clinical chronic GVHD occurred in 21 patients. Eighteen patients are alive 1-9 years (median = 4.2 years) after marrow grafting, 15 of whom are in continuous complete remission. The estimated probability of relapse within 2 years (+/- standard error) is 41 +/- 9% and the probability of relapse-free survival at 5 years is 28 +/- 7%. Major causes of death were recurrent leukemia, acute GVHD and interstitial pneumonia. Actuarial probabilities of survival, relapse and disease-free survival were not significantly different between those patients who did and those who did not have extramedullary disease after attaining first marrow remission.

Bone Marrow Transplantation↗
PubMed1987

Treatment of aplastic anemia with antithymocyte globulin, high-dose corticosteroids, and androgens.

A total of 46 patients with aplastic anemia (34 severe; 12 moderate) were treated with antihuman thymocyte globulin (ATG), high-dose methylprednisolone, and oxymetholone. Early symptoms of ATG toxicity included fever, rash, and bronchospasm. Signs of serum sickness also developed in 23 patients. Complications associated with high doses of steroids were hyperglycemia, hypertension, fluid retention, gastrointestinal hemorrhage, and aseptic necrosis of the hip. Other morbidity possible associated with steroid administration included seizures, arrhythmias, and headache with papilledema. Studies of elevated liver function necessitated discontinuation of androgen therapy in eight patients. A complete or partial hematological response was noted in 19 patients (41%). Of these, three have had recurrent cytopenias, of whom one has developed a myelodysplastic syndrome. There are currently 34 patients surviving, and 12 who have died. Actuarial survival at three years is 65%. These response and survival data are comparable to those of previous trials using ATG and androgens without high-dose steroids. A prospective, randomized trial is needed to determine whether the addition of high-dose corticosteroids to ATG does significantly increase the rate and frequency of response in order to justify the toxicity of this additional immunosuppressive therapy in the treatment of aplastic anemia.

Adult↗
PubMed1987

Preparation of red-blood-cell-depleted marrow for ABO-incompatible marrow transplantation by density-gradient separation using the IBM 2991 blood cell processor.

Thirty patients who had major ABO blood group incompatibility with their HLA-matched donors underwent allogeneic marrow transplantation after removal of red blood cells (RBC) from donor marrow by Ficoll-Diatrazoate (F-D) separation using the IBM 2991 blood cell processor. We selected the IBM 2991 because we were interested in obtaining information about RBC-depleted mononuclear cells for monoclonal antibody and complement incubation of marrow. The median residual marrow RBC volume was 2.6 ml (1.2% of the original volume) and marrow infusion was well tolerated in every instance. The median doses of nucleated and mononuclear cells were 8.7 X 10(7)/kg and 2.2 X 10(7)/kg recipient weight, respectively, representing median marrow total nucleated and mononuclear cell losses of 63.4% and 52.9%, respectively. The median CFU-GM loss was 52.4%. Four patients died 13-21 days after marrow infusion and were unevaluable for engraftment. One patient failed to achieve engraftment and received a second transplant on day 36 from a second donor. One patient with myelofibrosis had poor engraftment and died on day 177 with low peripheral blood counts. For evaluable patients, no significant differences were observed in the rate of recovery of peripheral blood granulocyte or platelet counts between those receiving RBC-depleted marrow or ABO-matched unprocessed marrow. However, posttransplant red cell transfusion requirements were increased and transfusion independence delayed in patients receiving RBC-depleted marrow as compared to patients receiving unprocessed marrow. We concluded that red cell depletion using the IBM 2991 was effective in removing red cell, but resulted in significant and variable hematopoietic cell losses which may have contributed to graft failure in at least one patient. Such cell losses appear to be inherent in both manual and semiautomated methods for F-D cell separation.

ABO Blood-Group System↗
PubMed1987

Treatment of preleukemic syndromes with marrow transplantation.

Thirty patients with advanced preleukemic syndromes were treated with marrow transplantation. Most cases were diagnosed by the presence of peripheral pancytopenia and a diagnostic marrow examination but in 6 of the 30 patients pretransplant chromosome studies were instrumental in establishing the diagnosis. Three patients prepared for transplantation with cyclophosphamide alone recurred with their disease within 6 months of transplantation. The other 27 patients were treated with cyclophosphamide and total body irradiation. Twenty of these 27 patients had preleukemia not associated with prior therapy or severe marrow fibrosis. Thirteen of these 20 are alive and well 9 to 56 months from transplant and 7 died, 4 of interstitial pneumonia, 2 of candida septicemia, and 1 of disseminated zoster. There have been no disease recurrences in this group. The remaining preleukemic patients, which include 3 patients transplanted for preleukemia secondary to prior therapy and 4 patients transplanted for preleukemia associated with severe marrow fibrosis, have all died. Major problems in these patients included disease recurrence (2 cases) and, in those with severe marrow fibrosis, graft failure (2 cases). These results suggest that for patients with life-threatening pancytopenia due to spontaneous preleukemia without severe marrow fibrosis, marrow transplantation can prolong disease-free survival and may result in cure of the disease.

Bone Marrow Transplantation↗
PubMed1986

Methotrexate and cyclosporine compared with cyclosporine alone for prophylaxis of acute graft versus host disease after marrow transplantation for leukemia.

We treated 93 patients who had acute nonlymphoblastic leukemia in the first remission or chronic myelocytic leukemia in the chronic phase (median age, 30 years) with high-dose cyclophosphamide and fractionated total-body irradiation, followed by infusion of marrow from an HLA-identical sibling. To evaluate postgrafting prophylaxis for graft versus host disease, we studied these patients in a sequential, prospective, randomized trial that compared the effect of a combination of methotrexate and cyclosporine (n = 43) with that of cyclosporine alone (n = 50). All patients had evidence of sustained engraftment. A significant reduction in the cumulative incidence of grades II to IV acute graft versus host disease was observed in the patients who received both methotrexate and cyclosporine (33 percent), as compared with those who were given cyclosporine alone (54 percent) (P = 0.014). Seven patients who received cyclosporine alone acquired grade IV acute graft versus host disease, as compared with none who received both methotrexate and cyclosporine. Thirty-five of the 43 patients given both methotrexate and cyclosporine and 31 of the 50 patients given cyclosporine are alive as of this writing, at 4 months to 2 years (median, 15 months); the actuarial survival rates in the two groups at 1.5 years were 80 percent and 55 percent, respectively (P = 0.042). We conclude that the combination of methotrexate and cyclosporine is superior to cyclosporine alone in the prevention of acute graft versus host disease after marrow transplantation for leukemia, and that this therapy may have a beneficial effect on long-term survival.

Acute Disease↗