1.
Use of leukocyte-depleted platelets and cytomegalovirus-seronegative red blood cells for prevention of primary cytomegalovirus infection after marrow transplant
Bowden RA, Slichter SJ, Sayers MH, Mori M, Cays MJ, Meyers JD
Blood. 1991;78((1):):246-50.
Abstract
Seventy-seven cytomegalovirus (CMV)-seronegative marrow transplant patients were randomized in a prospective controlled trial comparing the use of leukocyte-depleted platelets plus CMV-seronegative red blood cells with standard unscreened blood products for the prevention of primary CMV infection during the first 100 days after transplant. Eligible patients included CMV-seronegative patients undergoing autologous transplant or seronegative patients undergoing allogeneic transplant for aplastic anemia or non-hematologic malignancy who had seronegative marrow donors. Patients and marrow donors were serologically screened for CMV and randomized before conditioning for transplant and followed for CMV infection with weekly cultures of throat, urine, and blood and with weekly CMV serologies until day 100 after transplant. Leukocyte-depleted platelets were prepared by centrifugation, a procedure that removed greater than 99% of leukocytes. There were no CMV infections observed in 35 evaluable treatment patients compared with seven infections in 30 evaluable control patients (P = .0013). There was no statistically significant difference in the mean number of platelet concentrates in the treatment patients (164 concentrates) compared with the control patients (126 concentrates). Leukocyte-depleted platelets plus CMV-seronegative red blood cells are highly effective in preventing primary CMV infection after marrow transplant.
2.
Cytomegalovirus (CMV)-specific intravenous immunoglobulin for the prevention of primary CMV infection and disease after marrow transplant
Bowden RA, Fisher LD, Rogers K, Cays M, Meyers JD
Journal of Infectious Diseases. 1991;164((3):):483-7.
Abstract
Cytomegalovirus (CMV)-specific immunoglobulin (IVIG) was evaluated in a randomized controlled trial in CMV-seronegative marrow transplant patients with seropositive marrow donors for the prevention of primary CMV infection during the first 100 days after transplant. Patients received 200 mg/kg CMV IVIG on days 8 and 6 before transplant, the day after transplant, weekly for the first month, and then every 2 weeks to complete 10 doses. Patients were followed with weekly CMV cultures and serologic studies and for clinical and histologic evidence of CMV disease. Sixty patients were evaluable in each group. There was significantly less CMV excretion (P = .04) and viremia (P = .01) in the treatment group. However, the incidence of CMV disease including CMV pneumonia, CMV enteritis, and CMV syndrome (fever, leukopenia, hepatitis) was not statistically different. There was also no difference in median time of onset of CMV infection or disease, median number of hospital days, or survival between the two groups.
3.
Immunomodulatory and antimicrobial efficacy of intravenous immunoglobulin in bone marrow transplantation
Sullivan KM, Kopecky KJ, Jocom J, Fisher L, Buckner CD, Meyers JD, Counts GW, Bowden RA, Peterson FB, Witherspoon RP,, et al
New England Journal of Medicine. 1990;323((11):):705-12.
Abstract
BACKGROUND Graft-versus-host disease (GVHD) and infection are major complications of allogeneic bone marrow transplantation. Since intravenous immunoglobulin has shown benefit in several immunodeficiency and autoimmune disorders, we studied its antimicrobial and immunomodulatory role after marrow transplantation. METHODS In a randomized trial of 382 patients, transplant recipients given immunoglobulin (500 mg per kilogram of body weight weekly to day 90, then monthly to day 360 after transplantation) were compared with controls not given immunoglobulin. By chance, the immunoglobulin group included more patients with advanced-stage neoplasms; otherwise, the study groups were balanced for prognostic factors. RESULTS Control patients seronegative for cytomegalovirus who received seronegative blood products remained seronegative, but seronegative patients who received immunoglobulin and screened blood had a passive transfer of cytomegalovirus antibody (median titer, 1:64). Among the 61 seronegative patients who could be evaluated, none contracted interstitial pneumonia; among the 308 seropositive patients evaluated, 22 percent of control patients and 13 percent of immunoglobulin recipients had this complication (P = 0.021). Control patients had an increased risk of gram-negative septicemia (relative risk = 2.65, P = 0.0039) and local infection (relative risk = 1.36, P = 0.029) and received 51 more units of platelets than did immunoglobulin recipients. Neither survival nor the risk of relapse was altered by immunoglobulin. However, among patients greater than or equal to 20 years old, there was a reduction in the incidence of acute GVHD (51 percent in controls vs. 34 percent in immunoglobulin recipients; P = 0.0051) and a decrease in deaths due to transplant-related causes after transplantation of HLA-identical marrow (46 percent vs. 30 percent; P = 0.023). CONCLUSIONS Passive immunotherapy with intravenous immunoglobulin decreases the risk of acute GVHD, associated interstitial pneumonia, and infections after bone marrow transplantation.
4.
Cytomegalovirus immune globulin and seronegative blood products to prevent primary cytomegalovirus infection after marrow transplantation
Bowden RA, Sayers M, Flournoy N, Newton B, Banaji M, Thomas ED, Meyers JD
New England Journal of Medicine. 1986;314((16):):1006-10.
Abstract
In an attempt to prevent primary cytomegalovirus infection after marrow transplantation, we randomly assigned 97 patients who were seronegative for antibody to cytomegalovirus before transplantation to receive one of the following: (1) both intravenous cytomegalovirus immune globulin and seronegative blood products (23 patients); (2) seronegative blood products alone (28 patients); (3) globulin alone (22 patients); or (4) neither treatment (24 patients). Patients not assigned to receive seronegative blood products received unscreened blood products from random donors. The incidence of cytomegalovirus infection according to study group among patients in the study for at least 62 days was 5 percent, 13 percent, 24 percent, and 40 percent, respectively. Among 57 patients with seronegative marrow donors, those who received seronegative blood products had significantly less infection (1 of 32) than those who received standard blood products (8 of 25, P less than 0.007). In contrast, the use of seronegative blood products did not appear to prevent cytomegalovirus infection among patients with seropositive marrow donors. The possibility that cytomegalovirus immune globulin as used in this study can prevent cytomegalovirus infection or ameliorate cytomegalovirus disease was not confirmed, and it cannot be recommended for routine use without additional study.
5.
Prevention of cytomegalovirus infection by cytomegalovirus immune globulin after marrow transplantation
Meyers JD, Leszczynski J, Zaia JA, Flournoy N, Newton B, Snydman DR, Wright GG, Levin MJ, Thomas ED
Annals of Internal Medicine. 1983;98((4):):442-6.
Abstract
In an effort to prevent cytomegalovirus infection among seronegative patients having marrow transplants, a globulin with high antibody levels against cytomegalovirus was given before and for 11 weeks after transplantation in a randomized trial. Among 36 patients who received no prophylactic granulocyte transfusions, globulin recipients had significantly fewer infections than controls (2 of 17 versus 8 of 19, p = 0.05 by Fisher's exact test and p = 0.03 by Mantel-Cox test). Conversely, infection rates were high and unchanged by globulin use among patients who received granulocytes from seropositive donors (7 of 8 recipients versus 6 of 7 controls). The lack of effect of the globulin among patients receiving transfusions of granulocytes from seropositive donors may suggest that the dose of antibody was insufficient or that antibody is ineffective against virus transmitted in granulocytes. We conclude that cytomegalovirus infection can be prevented by immunoprophylaxis in seronegative patients having marrow transplants who are not given granulocyte transfusions.