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Biomedical subjects

W G Ho

Publications and source records attributed to W G Ho.

63 records · Page 4Linked to original sources

Cytomegalovirus infections associated with leukocyte transfusions.

Patients randomized to receive or not to receive prophylactic leukocyte transfusions were evaluated prospectively for serologic, histologic, and cultural evidence of cytomegalovirus infection. Recipients of prophylactic leukocyte transfusions and control subjects were similar with regard to age, sex, underlying disease, immunosuppressive therapy, and number of other transfusions. The recipients of prophylactic leukocyte transfusions (mean, 23.1) had significantly more cytomegalovirus infections (19 of 31 versus seven of 27, p = 0.01) than did control patients receiving no leukocytes or only therapeutic leukocyte transfusions (mean, 3.8). Twenty-seven of 66 donors of leukocytes were seropositive for cytomegalovirus complement-fixation antibody, but cytomegalovirus was not isolated from any of 62 leukocyte transfusions cultured for virus. These results are consistent with the hypothesis that latent cytomegalovirus may be present in leukocytes of blood donors with previous cytomegalovirus infection and after transfusion may be activated to produce active cytomegalovirus infection.

Adolescent↗

Cure of aplastic anaemia in paroxysmal nocturnal haemoglobinuria by marrow transfusion from identical twin: Failure of peripheral-leucocyte transfusion to correct marrow aplasia.

The ability of syngeneic peripheral leucocytes to cure marrow aplasia was tested in a patient with paroxysmal nocturnal haemoglobinuria (P.N.H.). Transfusion of 7.1X10(10) white cells obtained by leucopheresis from an identical-twin donor, providing 3.4X10(4) myeloid progenitors (C.F.U.-C)/kg, failed to improve marrow function within two months. In contrast, transfusion of 1.3X10(10) nucleated bone-marrow cells, representing 6.4X10(4) C.F.U.-C/kg, from the same donor resulted in prompt bone-marrow recovery. These observations support the hypothesis that aplastic anaemia in P.N.H. is a stem-cell defect that may be corrected by the simple infusion of relatively small numbers of normal bone-marrow cells. They also seem to indicate a distinct advantage of marrow cells over peripheral-blood mononuclear cells in their ability to correct marrow aplasia.

Adult↗

Pneumococcal infections after human bone-marrow transplantation.

Seven of 26 long-term survivors (greater than 7 months post-transplant) of bone-marrow transplantation developed penicillin-sensitive pneumococcal infections more than 7 months after transplantation. One patient had two infections. Six of eight infections were associated with pneumococcal bacteremia, and Streptococcus pneumoniae type 6A was isolated in three cases. Two infections were fatal. All patients had normal nematopoietic function, and none was receiving immunosuppressive therapy. The development of pneumococcal infection was significantly associated with males and with abnormally low or high serum IGG and IgM levels but not with graft-versus-host disease. Serum opsonic activity for S. pneumoniae type 6A was decreased in six of the seven patients when compared to normal pooled serum in an in-vitro bactericidal assay. Four of the six patients with impaired opsonic activity had low serum antibody levels for S. pneumoniae type 6A capsular polysaccharide, while the other two patients had low serum CH100 complement activity. Bone-marrow transplant recipients have an increased susceptibility to pneumococcal infections and should be evaluated for prophylactic penicillin or pneumococcal vaccination.

Adolescent↗

Isolation, cryopreservation, and autotransplantation of human stem cells.

We have used cryopreserved autologous hematopoietic cells to repopulate bone marrow of patients receiving intensive chemotherapy and radiation. We employed the technique of density step centrifugation to concentrate stem cells from whole bone marrow. The concentrate of cells was frozen in vials using dimethyl sulphoxide (DMSO) as a cryo-protective agent and was stored in the vapor phase of liquid nitrogen. Test vials were thawed and assayed for myeloid stem cells (CFU-C) to determine the potential of the larger marrow aliquot. These test values were compared to the recovery of cells and CFU-C when the marrow was used for autotransplantation. The return of hematopoietic function after autotransplantation was evaluated and correlated with the dosage of cells and CFU-C infused.

Bone Marrow Cells↗

Bone-marrow transplantation in acute leukaemia.

Survival in 33 patients with resistant leukaemia treated by marrow transplantation was compared with that of 37 matched patients treated by conventional and experimental chemotherapy. All patients in the transplant group were rendered free of detectable leukaemia for periods of from 36 days to more than 2 1/2 years, while only 6 patients in the chemotherapy group achieved a haematological remission. Overall survival in both groups was poor; however, 5 patients (15%) in the transplant group remain alive and in haematological remission 1--2 1/2 years after transplantation, while no patient in the chemotherapy group survived longer than 13 months. Bone-marrow transplantation appears to offer a small but distinct possibility of long-term survival in patients with acute leukaemia resistant to conventional therapy.

Adolescent↗

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↗