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Biomedical subjects

R E Champlin

Publications and source records attributed to R E Champlin.

208 records · Page 12Linked to original sources

Transplantation of ABH incompatible bone marrow: gravity sedimentation of donor marrow.

A simple technique to separate erythrocytes from bone marrow by sedimentation under gravity after addition of hydroxyethyl starch is described. This method of removing red blood cells from the donor marrow was evaluated in 23 consecutive allogeneic bone marrow transplants between ABH-incompatible individuals. Infusion of the separated marrow was well tolerated, i.e. graft-rejection did not occur, and sustained engraftment was documented in all evaluable cases. This technique obviates the need for cumbersome and potentially hazardous large volume plasma exchange that is commonly utilized to deplete recipient isohaemagglutinins prior to transplantation.

ABO Blood-Group System↗

Case problems in bone marrow transplantation. I. Graft failure in aplastic anemia: its biology and treatment.

An unusual case of graft failure following bone marrow transplantation for aplastic anemia is reported in which the patient had delayed and incomplete recovery of hematopoiesis despite documentation of sustained engraftment. The pathophysiology of graft failure following bone marrow transplantation is discussed and recent advances in pretransplant immunosuppressive therapy to prevent graft rejection are reviewed.

Adolescent↗

Safety and tolerance of recombinant leukocyte A interferon in bone marrow transplant recipients.

Five bone marrow transplant recipients with cytomegalovirus infections were treated with pure recombinant leukocyte A interferon produced by recombinant DNA technology from Escherichia coli. All five patients had documented interstitial pneumonia. The daily intramuscular dose of interferon ranged from 18 X 10(6) to 50 X 10(6) U; the mean duration of therapy was 11.0 days (range, 5 to 18 days). Two patients recovered, one improved, and two died. Clinical side effects (usually fever and chills) occurred in three patients. A 60% or greater reduction in the pretherapy peripheral granulocyte counts occurred in four patients, and four patients had a 37 to 80% reduction in their pretherapy platelet counts. Hematological toxicity was reversible, and there was no loss of marrow graft function. The toxicity of pure recombinant leukocyte A interferon in marrow transplants is similar to that of partially pure leukocyte interferon derived from human cells. Further controlled studies to establish the efficacy of recombinant leukocyte A interferon in marrow transplants are warranted but may be limited by hematological toxicity.

Adult↗

Pneumococcal vaccination of recipients of bone marrow transplants.

A 14-valent pneumococcal vaccine was administered to 39 recipients of allogeneic bone marrow transplants, and their type-specific antibody responses were compared with normal control subjects. Preimmunization antibody levels in patients were twofold to 12-fold lower than those levels in control subjects for all serotypes. Mean postimmunization antibody levels for each serotype were also considerably lower in patients (range, 56 to 859 ng of antibody nitrogen per milliliter) than in control subjects (range, 727 to 5,626 ng/mL). Poor antibody responses were primarily associated with early vaccination after transplantation, corticosteroid therapy for graft-v-host disease and other illnesses, and the male sex. Antibody responses of patients not given corticosteroids and vaccinated more than seven months after transplantation improved with time after transplantation. Postvaccination infection occurred in five patients who were vaccinated early after transplantation. Pneumococcal vaccination has limited potential for providing protection in marrow transplant recipients except in the cases of those patients who are not receiving corticosteroids and are vaccinated more than seven months after transplantation.

Adolescent↗

High-dose combined-modality therapy and autologous bone marrow transplantation in resistant cancer.

Fourteen patients with resistant cancers received high-dose chemotherapy and total body irradiation followed by rescue with autologous cryopreserved bone marrow cells. In seven patients, disease has remained in remission for periods up to two years. These data indicate that effectiveness of high-dose combined-modality therapy and bone marrow autotransplantation in patients with resistant cancer. The high incidence of non-marrow toxicity may be reduced by the use of this modality before patients have received extensive therapy.

Adolescent↗

Aplastic anemia: biology and treatment.

Aplastic anemia is characterized by decreased bone marrow function with inadequate production of erythrocytes, granulocytes, and platelets. Marrow failure may be caused by absence of or defects in hematopoietic stem cells, abnormalities of the bone marrow microenvironment, ineffective cell-to-cell interactions, or immune disorders. Although most patients with aplastic anemia have normal immunity, some have abnormalities of T- and B-lymphocytes. Rare patients have an immune cause of marrow failure. Treatment of aplastic anemia involves blood transfusions and withdrawal of potential causal factors. Efforts to stimulate hematopoiesis with androgens, corticosteroids, and other drugs have been largely unsuccessful. Some patients may recover after treatment with antithymocyte globulin or other immunosuppressive agents. Bone marrow transplantation is the preferred treatment for patients with severe aplastic anemia who have a human-leukocyte-antigen-identical related donor. Transplants of hematopoietic stem cells obtained from alternative sources, such as fetal liver cells or stem cells from long-term, in-vitro cultures, also may be useful.

Androgens↗

Ganciclovir therapy for cytomegalovirus infections in recipients of bone marrow transplants and other immunosuppressed patients.

The efficacy and safety of ganciclovir were evaluated for the treatment of 39 life-threatening or sight-threatening cytomegalovirus (CMV) infections in recipients of bone marrow transplants (15 patients), recipients of liver or renal transplants (8 patients), patients with AIDS (11 patients), and one patient each with lymphoma or systemic lupus erythematosus. Twenty-eight (72%) of 39 CMV infections improved during ganciclovir therapy, which was associated with elimination of CMV from cultures. Improvement occurred more frequently in patients with viremia, fever, and wasting (8 of 8), hepatitis (3 of 4), retinitis (5 of 5), or colitis (1 of 1), than in patients with pneumonia (11 of 21). Only two of nine marrow transplant recipients with CMV pneumonia survived, as compared with nine of 12 other immunosuppressed patients with pneumonia. However, all six marrow transplant recipients who were treated for CMV viremia, fever, and wasting without pneumonia survived. Neutropenia was the only adverse reaction associated with ganciclovir therapy and was more frequent in patients with AIDS (6 [55%] of 11) than in transplant recipients (5 [20%] of 25). These results suggest that ganciclovir is of clinical benefit for immunosuppressed patients with serious CMV infections. For bone marrow transplant recipients, ganciclovir may be more effective when used prophylactically or earlier in the course of CMV infection before the development of pneumonia.

Acquired Immunodeficiency Syndrome↗

Cytomegalovirus infections after allogeneic bone marrow transplantation.

Cytomegalovirus (CMV) infection occurs in approximately 50% of all recipients of allogeneic bone marrow transplants and is seen more frequently in CMV-seropositive patients than in CMV-seronegative patients. Sources of infection include reactivation of latent endogenous virus, blood products from CMV-seropositive blood donors, and the use of marrow from a CMV-seropositive donor for a CMV-seronegative recipient. The most common and severe clinical syndrome associated with CMV infection in allogeneic transplant recipients is interstitial pneumonia, which occurs in approximately 15% of patients. Risk factors for CMV pneumonia include old age, conditioning with total-body irradiation, and severe graft-vs.-host disease. The rapid diagnosis of CMV pneumonia has been facilitated by immunochemical staining of bronchoalveolar lavage fluid or by centrifugation of cell cultures with CMV monoclonal antibodies. The treatment of CMV pneumonia remains problematic, but therapy with a combination of intravenous immune globulin (IVIG) plus ganciclovir has resulted in survival rates substantially better than those achieved in previous trials of antiviral therapy. In CMV-seronegative patients, CMV infection and pneumonia can be prevented or modified by the use of CMV-seronegative blood products and IVIG. IVIG may also have the additional benefits of preventing other infectious complications and graft-vs.-host disease in patients receiving CMV-seronegative blood products. For CMV-seropositive patients, effective prophylaxis for CMV reactivation and pneumonia has not yet been established, but a clinical trial of prophylactic ganciclovir is now under way.

Bone Marrow Transplantation↗

Prognostic factors in bronchoalveolar lavage in 77 patients with bone marrow transplants.

OBJECTIVE: To study the prognostic implications of the following factors in bronchoalveolar lavage (BAL) specimens in bone marrow transplant (BMT) patients: number of lymphocytes per high-power field (HPF), presence of hemosiderin-laden macrophages (HLMs), presence of infections and presence of reactive epithelial cellular changes in bronchial and alveolar cells. STUDY DESIGN: A retrospective study of 77 bone marrow transplant patients who required BAL. Each specimen was studied for the number of lymphocytes per HPF, presence of HLMs, presence of infection and presence of reactive epithelial cells. RESULTS: Patients who had < or = 5 lymphocytes per HPF had a much higher death rate than did patients who had > 5 lymphocytes per HPF (P < .001). Eighty-nine percent of patients who had < or = 5 lymphocytes per HPF died within 30 days of undergoing BAL (P < .001). Patients without HLMs had a better prognosis than did patients with HLMs (P < .005). Thirty-six documented viral or fungal infections occurred in 33 patients. Patients with infections had a greater chance of dying than did those who were infection free (P < .05). Multiple logistic regression analysis showed that the previous three factors are statistically significant. Reactive epithelial cellular changes were seen primarily in patients with autologous BMT (11 of 14 cases) and in those with hematologic malignancies, but they had no statistical significance prognostically. CONCLUSION: The following factors in BAL have a good prognostic value: number of lymphocytes > 5 per HPF, absence of HLMs and absence of infections. Reactive epithelial cellular changes have no prognostic value.

Bone Marrow Transplantation↗