1.
Reduced dose intravenous immunoglobulin does not decrease transplant-related complications in adults given related donor marrow allografts
Feinstein LC, Seidel K, Jocum J, Bowden RA, Anasetti C, Deeg HJ, Flowers ME, Kansu E, Martin PJ, Nash RA, et al
Biology of Blood & Marrow Transplantation. 1999;5((6):):369-78.
Abstract
Graft-vs.-host disease (GVHD) and infection are major complications of allogeneic bone marrow transplantation. Intravenous immunoglobulin (IVIg) given at a dose of 500 mg/kg/wk has been shown to decrease the risk of acute GVHD, interstitial pneumonia, and infection in adults early after allogeneic transplantation. The current study is a controlled trial to determine whether a lower total dose of IVIg given with pretransplant loading reduces the incidence of transplant-related complications. In a randomized trial of 241 patients > or =20 years of age who were given related donor marrow allografts, 121 individuals receiving Ig prophylaxis (500 mg/kg/d loading from day -6 to -1 and then 100 mg/kg every 3 days from day 3 to 90) were compared with 120 control patients who did not receive IVIg. Randomization was stratified by human leucocyte antigen-matching, remission status of malignancy, GVHD prophylaxis, and cytomegalovirus (CMV) serology. The study was powered to detect a reduction in acute GVHD by 18% and a decrease in transplant-related mortality by 17%. Pretransplant IVIg loading and posttransplant maintenance achieved median serum IgG levels >1350 mg/dL, which were approximately twofold greater than the untreated controls (p<0.01). White blood cell and platelet recoveries were similar for the two groups, although control patients required fewer units of platelets per day (2.5 vs. 3.3, p = 0.008). No significant differences in the incidence of CMV infection, interstitial pneumonia, or bacteremia were observed. The incidence of acute GVHD did not differ between the two groups; however, acute GVHD was less frequent among IVIg recipients achieving maximum serum IgG levels >3000 mg/dL (60 vs. 79%). Neither transplant-related mortality nor disease-free survival was significantly altered by Ig prophylaxis. However, the cumulative incidence of relapse of malignancy was higher in IVIg recipients than in controls (31 vs. 18%, p = 0.03). Multivariable regression analysis demonstrated a 1.89 increased relative risk of relapse for individuals given IVIg (p = 0.021). We conclude that pretransplant loading and a shorter course and lower total dose of IVIg prophylaxis did not appear to decrease the risk of acute GVHD or mortality among adults receiving related donor marrow transplants. Note, IVIg administration may be associated with an increased risk of recurrent malignancy, a finding that warrants further investigation.
2.
A comparison of filtered leukocyte-reduced and cytomegalovirus (CMV) seronegative blood products for the prevention of transfusion-associated CMV infection after marrow transplant
Bowden RA, Slichter SJ, Sayers M, Weisdorf D, Cays M, Schoch G, Banaji M, Haake R, Welk K, Fisher L
Blood. 1995;86((9):):3598-3603.
3.
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.
4.
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.