Search PubMed⌕ Search

Biomedical subjects

F R Appelbaum

Publications and source records attributed to F R Appelbaum.

467 records · Page 26Linked to original sources
PubMed1979

The hemostatic imbalance of plasma-exchange transfusion.

Plasma exchange has been proposed as a treatment for multiple disorders. Three patients with amyotropic lateral sclerosis, who were hemostatically normal, were studied through a total of 11 4-liter exchanges. Plasma was replaced by an equal volume of 5% albumin or 5% plasma protein fraction. Serial studies revealed that immediately after the exchange transfusion, there was significant prolongation of the prothrombin, partial thromboplastin, and thrombin times with reduction of the fibrinogen and antithrombin III levels. Factors V, VII-X, IX, and X were all significantly decreased, as were the factor VIII antigen, procoagulant, and the ristocetin cofactor activities. Platelet counts were obtained before and after exchanges and revealed significant decreases. Four hours after exchange, all parameters remained abnormal except the factor IX, ristocetin cofactor, and factor VIII procoagulant activities. By 24 hr, all hemostatic parameters had returned to normal. These studies indicate that plasma-exchange transfusion with material devoid of coagulation factors results in a coagulation defect that may be of clinical significance in a hemostatically compromised patient.

Amyotrophic Lateral Sclerosis↗
PubMed1978

[Long-term, complete remission in non-Hodgkin's lymphoma following high-dosage combination therapy with or without autologous bone marrow transplantation].

22 patients with malignant non-Hodgkin lymphoma resistant to conventional chemotherapy were treated with high-dose combination chemotherapy followed in the first 12 patients by infusion of their cryopreserved autologous bone marrow. The next 10 patients received chemotherapy alone. Four patients died shortly after chemotherapy. Four patients remain in unmaintained remission 40, 30, 20 and 8 months after treatment. Patients receiving cryopreserved marrow recovered leukocyte, granulocyte and platelet function significantly faster and had significantly fewer febrile days than did controls. These findings demonstrate that high dose combination chemotherapy may benefit some patients unresponsive to conventional chemotherapy, and that cryopreserved bone marrow can speed hematopoetic recovery and be of clinical benefit to the patient.

Antineoplastic Agents↗
PubMed1978

Prolonged complete remission following high dose chemotherapy of Burkitt's lymphoma in relapse.

Fourteen patients with American Burkitt's lymphoma resistant to conventional chemotherapy were treated with high-dose combination chemotherapy and intensive supportive care. Four patients died shortly after chemotherapy, 3 of an acute carditis. All ten remaining patients demonstrated tumor regression and 3 remain in prolonged complete unmaintained remission 29+, 19+, and 9+ months after treatment. These findings demonstrate that high-dose chemotherapy will benefit some patients with Burkitt's lymphoma unresponsive to conventional chemotherapy, but the medullary and extramedullary toxicity of this treatment strategy remains a formidable obstacle.

Adolescent↗
PubMed1978

Sequential combination chemotherapy (containing high-dose cyclophosphamide) for metastic osteogenic sarcoma.

Eleven patients with metastatic osteogenic sarcoma were treated with cyclophosphamide, adriamycin, and, in some cases, high-dose methotrexate. In the event of metastatic progression, the dose of cyclophosphamide was escalated by increasing the number of consecutive daily infusions (dose, 45 mg/kg/day). The results indicate that metastatic osteogenic sarcoma is marginally responsive to adriamycin and cyclophosphamide but rarely responsive to high-dose methotrexate as administered in this trial. The response of metastatic lesions was not improved by escalating the dose of cyclophosphamide.

Adolescent↗
PubMed1978

Successful engraftment of cryopreserved autologous bone marrow in patients with malignant lymphoma.

In an effort to evaluate the possible utility of cryopreserved autologous bone marrow infusions in man, 22 patients with malignant lymphoma resistant to conventional chemotherapy were treated with high-dose chemotherapy. This was followed in 12 patients by an infusion of their cryopreserved autologous bone marrow; 10 patients received chemotherapy alone and serve as controls. Following chemotherapy, severe leukopenia (less than 100 leukocytes/mm3) lasted 6-10 (median 8) days in patients receiving cryopreserved marrow, compared to 10-29 (median 16) days in controls (p less than 0.001). Recovery to 1000 leukocytes/mm3 occurred 10-18 (median 13) days after chemotherapy in autograft recipients but was delayed until 12-38 (median 23) days after chemotherapy in controls (p less than 0.001). Autografted patients also recovered granulocyte and platelet function significantly faster and had significantly fewer febrile days after chemotherapy than did controls. Cryopreserved autologous bone marrow infusions can hasten hemopoietic recovery in man after high-dose chemotherapy; this earlier reconstitution may be of clinical benefit to the patient.

Adolescent↗
PubMed1977

Migration of transfused granulocytes in leukopenic dogs.

Although granulocyte transfusion therapy has been shown to be effective in infected granulocytopenic animals and humans, the relative effectiveness of granulocytes (PMN) harvested by continuous flow centrifugation (CFC) or by continuous flow filtration leukapheresis (FL) remains uncertain. Studies in vitro of morphology and granulocyte functions have suggested cells collected by FL may be damaged. To compare the function in vivo of granulocytes collected by different methods, dogs were made granulocytopenic with cyclophosphamide (CYT) and then transfused with granulocytes collected by CFC or FL. The local neutrophil mobilization (LNM) through a standard skin abrasion into a chamber containing a strong chemoattractant, autologous serum, was measured. Greater LNM was found after transfusions of CFC PMN than after transfusions of the same number of FL PMN (p less than 0.0003). This difference persisted even when the dose of FL PMNs was four times greater than that of CFC mn and when the FL donor was pretreated with steroids (p less than 0.001). These results suggest that during filtration leukapheresis, granulocytes are functionally altered and that their function in vivo may be compromised.

Animals↗
PubMedDate not supplied

Treatment of non-Hodgkin's lymphoma with chemoradiotherapy and allogenic marrow transplantation.

Twenty patients with disseminated non-Hodgkin's lymphoma who failed conventional combination chemotherapy were treated with high-dose chemoradiotherapy and marrow transplantation from an HLA-identical sibling. Four patients remain alive in complete remission from 153 to 784 days after transplant. The reason for failure in eight cases was persistence or relapse of lymphoma. In the other eight cases, death was due to a complication of the transplant procedure including interstitial pneumonia, veno-occlusive disease of the liver, graft-versus-host disease, or infection. These results appear similar to those previously observed in patients with acute leukemia in relapse in that a small but significant proportion of patients with otherwise end-stage disease may achieve prolonged complete remission after intensive chemoradiotherapy and allogeneic marrow transplantation.

Adolescent↗
PubMedDate not supplied

Phenotyping of canine lymphoma with monoclonal antibodies directed at cell surface antigens: classification, morphology, clinical presentation and response to chemotherapy.

Forty cases of naturally occurring canine lymphoma were studied using a panel of murine monoclonal antibodies which identify defined subsets of normal canine lymphocytes. The distribution of phenotypes was similar to that which is seen in man in that the majority (78 per cent) of canine lymphomas were of B-cell origin but a definite minority were phenotypically of T-cell (10 per cent) or non-B, non-T-cell (12 per cent) origin. The expression of Ia-like antigens was restricted to B-cell neoplasms. Within each histologic subgroup of canine lymphomas there was considerable heterogeneity of cell surface marker expression. Immunophenotype appeared to correlate with clinical presentation. Finally, the reactivity of lymphoma cells with murine monoclonal antibody DLy-6, an antibody which appears to react with a differentiation antigen on canine B and T cells, strongly predicted the outcome of initial induction chemotherapy in that all ten evaluable dogs with DLy-6-tumors achieved complete responses to initial chemotherapy while only four of 11 dogs with DLy-6+ tumors responded completely.

Animals↗
PubMedDate not supplied

Autologous bone marrow transplantation in adults with non-Hodgkin's lymphoma: a Southwest Oncology Group study.

Patients with non-Hodgkin's lymphoma (NHL) who fail conventional chemotherapy have a dismal outcome. Reports from single institutions utilizing high-dose chemoradiotherapy plus Autologous Bone Marrow Transplantation (ABMT) in this setting suggest three-year disease-free survival between 15-60 per cent. From 1985 to 1989 the Southwest Oncology Group performed a prospective multi-institutional study involving ABMT in relapsed/refractory NHL. Forty-five patients, ages 6-60 (median 38), with relapsed NHL were treated with high-dose cyclophosphamide (60 mg/kg/d x 2), total body irradiation (200 cGy/d x 6), and autologous unpurged bone marrow. Histologic subtypes included high grade lymphoma (10), intermediate grade lymphoma (33), and low grade lymphoma (2). Disease status pre-ABMT was sensitive relapse (16), resistant relapse (13), and untreated relapse (16). The actuarial three-year event-free survival and overall survival for all patients were 27 per cent and 38 per cent respectively. Causes of failure included regimen-related deaths (4), lack of response (10), or tumour progression (20) which occurred at a median of 5 months (1-22) post-ABMT and usually at previous sites of involvement. Response to salvage therapy pre-ABMT, a reflection of a tumour's biological behaviour, was the most important predictor of good outcome post-ABMT. This study confirms that a significant number of patients with recurrent NHL can achieve prolonged disease-free survival after ABMT.

Adolescent↗
PubMedDate not supplied

Consequences of prior alloimmunization during granulocyte transfusion.

The transfusion of leukocyte-containing blood products can lead to the production of antibodies to antigens on the surface of leukocytes. Such antibodies can be detected by a variety of techniques including assays for lymphocytotoxicity, granulocytotoxicity, and leukoagglutination. In order to evaluate the effect of preformed anti-leukocyte antibodies during granulocyte transfusion therapy, recipient beagles were sensitized to donor foxhound antigens. After being made granulocytopenic with cyclophosphamide, these animals were transfused with a set dose of granulocytes collected by continuous flow centrifugation. When compared to the results of similar transfusions to nonsensitized recipients, granulocyte transfusions to animals with preformed anti-leukocyte antibodies resulted in lower one-hour posttransfusion leukocyte increments (p less than .04) and in less migration of neutrophils through a skin abrasion into a chamber containing a strong chemoattractant, autologous serum (p less than .0001). Also, profound thrombocytopenia was found in sensitized animals, but not in nonsensitized recipients, one hour after the granulocyte transfusion.

Animals↗
PubMedDate not supplied

Lack of predictive value of antileukocyte antibody screening in granulocyte transfusion therapy.

To clarify the relationship between recipient presensitization and response to granulocyte (PMN) transfusion, we tested 187 non-HL-A matched donor-recipient pairs for the presence of antileukocyte antibody using granulocytotoxicity (G), lymphocytotoxicity (L), microleukoagglutination (M), and capillary leukoagglutination (C) assays. PMN increments per 10(11) transfused PMNs per square meter of body surface area, ascertained one hour following termination of transfusion, and the occurrence of nonhemolytic transfusion reactions, were correlated with the assay results. Although circulating anti-donor-leukocyte antibody was detected in 52 per cent of recipients, there was no statistically significant relationship between the presence of these antibodies and either PMN recovery or incidence of transfusion reaction. We conclude that the prospective use of these assays is of little value in predicting the recipient's response to PMN transfusion.

Blood Transfusion↗
PubMedDate not supplied

Use of in vitro assays in selection of compatible platelet donors.

Although HLA-matched platelet transfusions are of value in the support of some alloimmunized thrombocytopenic patients, poor posttransfusion increments can be observed following HLA-matched platelet transfusions and conversely good posttransfusion increments may result after HLA-mismatched platelet transfusions. We have explored the possibility that in vitro assays in addition to HLA typing might better select compatible donors for refractory recipients. Our studies suggested that a platelet migration inhibition assay is predictive of platelet transfusion responses in HLA-compatible and incompatible donor-recipient pairs, while lymphocytotoxicity is predictive of posttransfusion increments only in HLA-incompatible donor-recipient pairs. Granulocytotoxicity, microleukoagglutination, and capillary leukoagglutination showed no value in predicting platelet transfusion increments, either in HLA-compatible or incompatible donor-recipient pairs.

Anemia, Aplastic↗
PubMedDate not supplied

Surgical hypothermia in a patient with a cold agglutinin. Management by plasma exchange.

Cold agglutinins are a potential danger to patients who must be subjected to hypothermia. A patient with a cold agglutinin of moderate titer but broad thermal amplitude was to undergo hypothermia during aortic valve replacement. He was managed preoperatively with an eight-liter plasma exchange by continuous-flow centrifugation to remove the cold agglutinin. There were no adverse effects during or after hypothermia.

Agglutinins↗
PubMedDate not supplied

The use of bone marrow and peripheral blood stem cell transplantation in the treatment of cancer.

Since its first successful application 25 years ago, the clinical use of bone marrow and peripheral blood stem cell transplantation has increased dramatically. Transplantation allows for the administration of high doses of systematic chemotherapy and radiotherapy and confers an antitumor effect separate from the effects of chemotherapy. However,complications including toxicity of treatment, graft failure, and graft-versus-host disease exist. This article reviews the history and current use of bone marrow and peripheral blood stem cell transplantation and outlines new approaches for clinical application.

Bone Marrow Transplantation↗