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Biomedical subjects

R A Clift

Publications and source records attributed to R A Clift.

At least 127 records · Page 7Linked to original sources
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

Mycobacterial infections in marrow transplant patients.

Bone marrow transplant recipients undergo ablation of host immune defenses with total-body irradiation or high dose chemotherapy, or both. Over a 5.6-year period, mycobacterial infections were observed in 7 of 682 patients with leukemia who received marrow grafts. Four patients had pulmonary and three extrapulmonary infection. Granulomas were observed in the lungs of three patients, in the liver of one patient, and in the skin of one patient. Cultures revealed Mycobacterium tuberculosis in two patients, Mycobacterium fortuitum in two patients, and Mycobacterium kansasii in one patient. In the six patients treated with antimycobacterial therapy in either the pretransplant or posttransplant period, complete resolution of the infection was achieved. Pretransplant chest radiograph abnormalities suggesting mycobacterial infections should be aggressively evaluated in these immunocompromised hosts. Prophylaxis should be considered in marrow graft recipients with a well-established history of inadequately treated tuberculosis, previous Bacille Calmette-Guerin immunotherapy, known family contacts, recent skin test conversion, or past skin test positivity.

Adolescent↗
PubMed1983

Predictive factors in chronic graft-versus-host disease in patients with aplastic anemia treated by marrow transplantation from HLA-identical siblings.

One hundred ten of 175 patients with aplastic anemia conditioned by cyclophosphamide had sustained engraftment of marrow from human leukocyte antigen (HLA)-identical siblings and lived for more than 6 months. Forty-nine of the 110 patients developed chronic graft-versus-host disease between 85 and 464 days. Ninety-seven patients are alive from 1.4 to 11 years after engraftment; 13 died between 208 and 726 days. Twenty of the 36 surviving patients with chronic graft-versus-host disease have Karnofsky performance scores of 100%, 7 of 90%, 5 of 80%, 1 of 70%, 2 of 60%, and 1 of 40%. Our analysis, using a binary logistic regression model, identified three factors predicting chronic graft-versus-host disease: moderate to severe acute graft-versus-host disease with an estimated relative risk of 11.65; increasing patient age; and the use of viable donor buffy coat cells in addition to the marrow to prevent graft rejection. The last two factors were significant only in patients without acute graft-versus-host disease.

Adolescent↗
PubMed1983

Intensive chemoradiotherapy with autologous marrow transplantation for small cell carcinoma of the lung.

Ten patients with small cell carcinoma of the lung (seven with extensive and three with limited disease) underwent several courses of conventional therapy. The patients were then referred for autologous marrow transplantation, three during a complete response, six during a partial response, and one following no response. The pretransplantation regimen consisted of 120 mg/kg of cyclophosphamide followed by 800-1000 rad of total-body irradiation. In addition, six of the seven patients with extensive disease received high-dose nitrosourea. Following the infusion of cryopreserved autologous marrow, all patients achieved engraftment. Of the three patients without detectable tumor at the time of transplant, two died with tumor present and one survives without recurrence 27 months after transplantation. Of the other seven patients, two had a complete tumor response; both died of interstitial pneumonitis, one without detectable tumor and one with microscopic tumor at autopsy. One of the other five patients had a partial response, but all died of tumor progression. The median survival from initial therapy in patients with extensive disease was 9 months and with limited disease was 18.5 months.

Autopsy↗
PubMed1983

Marrow transplantation from HLA-identical siblings for treatment of aplastic anemia: is exposure to marrow donor blood products 24 hours before high-dose cyclophosphamide needed for successful engraftment?

The present study in patients with aplastic anemia was undertaken to determine whether exposure of recipients to donor blood products 24 hr before preparation with cyclophosphamide (1) enhanced the rate of sustained engraftment of marrow from HLA-identical siblings as suggested by animal experiments, (2) increased the rejection rate, in particular in transfused patients who may already have been exposed to donor antigens by blood products, or (3) was of no relevance to the outcome of transplantation of marrow from HLA-identical siblings. One-hundred fifty-five patients were studied, of whom 78 received blood products from the marrow donor 24 hr before cyclophosphamide and 77 did not. A binary logistic regression analysis was applied to the data, simultaneously considering five previously known risk factors for rejection. Results showed that preceding transfusion of donor blood products had neither a significant beneficial nor detrimental effect on the incidence of sustained engraftment.

Anemia, Aplastic↗
PubMed1983

Allogeneic marrow transplantation for acute nonlymphoblastic leukemia after first relapse.

Sixty-two patients with acute nonlymphoblastic leukemia in first relapse or second remission were treated with allogeneic marrow transplantation from HLA-matched siblings. In 17 patients (group 1), no attempt at reinduction of remission was made prior to transplantation. In 20 patients (group 2), attempts at inducing a second remission prior to transplantation were unsuccessful; and in 25 patients (group 3), a second remission was achieved. Five of 17 patients (29%) in group 1, 2 of 20 (10%) in group 2, and 5 of 25 (20%) in group 3 are surviving disease-free 2-6 yr after grafting. Early mortality from nonleukemic causes was equal in the 3 groups, but the risk of recurrent leukemia after transplantation was less in patients transplanted without attempts at reinduction (group 1). Among patients transplanted in relapse, those in early relapse (less than 30% blast cells in the marrow) appeared to do better than patients in florid relapse. The results obtained in group 1 are as good as or better than those achieved in patients transplanted in second or subsequent remission. Thus, for patients with acute nonlymphoblastic leukemia not transplanted in first remission, the optimal time for transplantation would appear to be as soon as possible after the first relapse.

Acute Disease↗
PubMed1983

Fanconi's anemia treated by allogeneic marrow transplantation.

Eight patients with Fanconi's anemia were given cyclophosphamide alone (seven patients) or combined with procarbazine and antithymocyte globulin (one patient) followed by marrow grafts from HLA-identical siblings. All patients had engraftment. Seven developed acute and three chronic graft-versus-host disease (GVHD). Three patients died with GVHD and infectious complications (days 19, 56, and 82) and one with an intracerebral hemorrhage (day 540). Four patients are surviving 647-3435 days after grafting, two are well, and two have chronic GVHD that is improving. These results show that Fanconi's anemia can be treated successfully by allogeneic marrow transplantation.

Anemia, Aplastic↗
PubMed1983

Marrow transplantation for patients with acute lymphoblastic leukemia: a long-term follow-up.

Twenty-two patients with acute lymphoblastic leukemia in second or subsequent remission and 26 with acute lymphoblastic leukemia in relapse were given cyclophosphamide (60 mg/kg on each of 2 days), total body irradiation (920 rad), and marrow transplants from HLA-identical siblings. With a minimum follow-up of more than 5 yr, an actuarial analysis shows a survival and apparent cure of 27% of the patients transplanted in remission and 15% of the patients transplanted in relapse.

Bone Marrow Transplantation↗
PubMed1982

Treatment of chronic granulocytic leukaemia in chronic phase by allogeneic marrow transplantation.

Ten patients with chronic granulocytic leukaemia in the chronic phase have been treated with chemoradiotherapy followed by transplantation of bone marrow from HLA-identical siblings. Engraftment was achieved in all patients, and Philadelphia chromosome disappeared from the nine patients who had it before transplantation. Four patients have died, three with interstitial pneumonitis and one with severe graft-versus-host disease (GvHD). Six patients are alive and well in complete clinical, cytogenetic, and haematological remission, 1-3 years after transplantation, despite complications in three patients (one had interstitial pneumonitis, one had mild veno-occlusive disease of the liver, and one had severe GvHD).

Adult↗
PubMed1982

Removal of specific antibody in vivo by whole blood immunoadsorption: preliminary results in dogs.

Effective immunoadsorption for removal of anti-red cell antibodies from plasma using affinity columns has been demonstrated. However, the requirement of a continuous-flow centrifuge to separate plasma increases the cost and complexity of the procedure. We have adapted red cell antigen immunoadsorption columns for use with whole blood. Effective and specific removal of anti-red cell antibodies was achieved in actively immunized dogs.

ABO Blood-Group System↗
PubMed1982

Allogeneic marrow transplantation for acute leukemia in relapse.

The results of allogeneic marrow transplantation in 75 patients with acute lymphoblastic leukemia and 63 patients with acute non-lymphoblastic leukemia in relapse are reviewed. The effects of various chemotherapeutic regimens added to the basic regimen of cyclophosphamide (Cy) 60 mg/kg given on each of two successive days followed by 1000 rad of total body irradiation (TBI) were evaluated. The regimens tested were dimethylbusulphan (DMB), 1,3-bis(2-chlorethyl)-1-nitrosourea (BCNU) and daunorubicin. Seventeen of 138 patients are alive between three and nine and a half years from transplantation. The addition of other chemotherapeutic agents to th basic Cy and TBI regimen did not decrease relapse frequency or prolong survival.

Adolescent↗
PubMed1982

Allogeneic marrow transplantation for acute non-lymphoblastic leukemia in relapse using fractionated total body irradiation.

Twenty-three patients with acute non-lymphoblastic leukemia in relapse were treated with cyclophosphamide, fractionated total body irradiation (200 rad/day for six days) and allogeneic marrow transplantation. Six patients are alive in remission 756-1306 days following transplantation. One patient died of infection on day 17 without evidence of engraftment; all others achieved sustained engraftment. Eight patients died of recurrent leukemia, four of interstitial pneumonitis, two of infection, one of veno-occlusive disease of the liver and one of cardiac failure. The median survival time was 181 days.

Adolescent↗
PubMed1982

Allogeneic marrow transplantation for patients with acute non-lymphoblastic leukemia in second remission.

Twenty-four patients with acute non-lymphoblastic leukemia (ANL) in second remission were transplanted from HLA-matched siblings. Twelve patients died of non-leukemic causes and four of recurrent leukemia. One patient is alive after relapse and seven patients are alive and free of disease 114-1907 days after transplantation. The first seven patients received 1000 rad total body irradiation (TBI) in a single exposure. The last 17 were entered on a randomized study to receive 1000 rad TBI as a single dose (seven patients) or 1200 rad TBI fractionated over six days (10 patients). Only one of the 10 patients receiving the fractionated TBI is alive and free of disease 786 days after transplantation while three of the seven receiving single-dose TBI remain in remission 114-541 days after grafting. Even if larger numbers of patients were accrued to this study, it is unlikely that the use of fractionated TBI would prove superior to single-exposure TBI. The actuarial analysis showed that the relapse rate for all 24 patients transplanted in second remission was 50% which was equivalent to patients with ANL transplanted in relapse. The disease-free survival two years after transplant was 24% for patients transplanted in second remission as compared to 26% for patients transplanted in relapse.

Adolescent↗
PubMed1982

Allogeneic marrow transplantation using fractionated total body irradiation in patients with acute lymphoblastic leukemia in relapse.

Six fractionated total body irradiation (TBI) regimens given over 2-7 days to a total midline dose of between 1200 and 1750 rads were evaluated in 41 patients with acute lymphoblastic leukemia in relapse. Cyclophosphamide 120 mg/kg was given prior to TBI in all cases, and dimethylbusulphan was added to cyclophosphamide and 1500 rad TBI in one regimen. Relapses occurred in all regimens. The overall disease-free survival of three of 41 patients was not different from previous studies with 1000 rad TBI given in a single dose. Graft-vs-host disease occurred in only 12 of 41 patients. Two of three disease-free survivors had significant graft-vs-host disease.

Adolescent↗