High-dose intravenous immunoglobulin therapy in neonatal immune haemolytic jaundice. High-dose intravenous immune globulin therapy for hyperbilirubinemia caused by Rh hemolytic disease. High-dose intravenous immunoglobulin therapy for rhesus haemolytic disease. Effectiveness of single versus double volume exchange transfusion in newborn infants with AB0 hemolytic disease. Intravenous immunoglobulin infusions for the prophylaxis of secondary cytomegalovirus infection. Randomized trial of granulocyte transfusions versus intravenous immune globulin therapy for neonatal neutropenia and sepsis. Effect on neutrophil kinetics and serum opsonic capacity of intravenous administration of immune globulin to neonates with clinical signs of early-onset sepsis. [Intravenous immunoglobulin in the treatment of neonatal septicemia]. Immunomodulatory and antimicrobial efficacy of intravenous immunoglobulin in bone marrow transplantation.
A controlled study was conducted to assess the role of high-dose i.v. immunoglobulin (HDIVIG) therapy in neonatal immune haemolytic jaundice. Patients with ABO and/or Rh incompatibilities proved by significant hyperbilirubinaemia (>204 mmol l(-1)), positive direct antiglobulin test and high reticulocyte count (> or =10%) were randomly assigned to receive either conventional phototherapy alone or phototherapy with high-dose i.v. immunoglobulin (1 g kg(-1), over 4 h) as soon as the diagnosis was established. Exchange transfusions were performed if serum bilirubin concentrations exceeded 290 mmol l(-1) and increased by more than 17 mmol l(-1) per h despite both treatment manoeuvres. Eight of 58 patients in the HDIVIG group required exchange transfusions, whereas it became necessary in 22 of 58 patients in the control group (p<0.001). The durations of phototherapy and hospitalization in terms of hours were significantly shorter in the HDIVIG group (p<0.05). No side effects of HDIVIG therapy were observed. In conclusion, HDIVIG therapy in newborns with ABO or Rh haemolytic diseases reduces haemolysis, serum bilirubin levels and the need for blood exchange transfusion, a procedure which has potential complications and carries a risk of mortality. We conducted a multicenter controlled trial to test the hypothesis that high-dose intravenous immune globulin (HDivIG) therapy can modulate bilirubin production and reduce the frequency of exchange transfusions in newborn infants with Rh hemolytic disease. Thirty-four patients with Rh incompatibility proved by positive direct antiglobulin test (Coombs test) results were randomly assigned to receive conventional treatment including phototherapy, with or without additional HDivIG therapy at 500 mg/kg given for a 2-hour period as soon as the diagnosis was established. Exchange transfusions were performed if serum bilirubin concentrations exceeded the modified curves of Polácek by more than 2 mg/dl. Two patients were excluded because of protocol violations. The results in 32 infants were analyzed. In the HDivIG group, 2 (12.5%) of 16 children required exchange transfusions, whereas it became necessary in 11 (69%) of 16 children in the control group (p less than 0.005). Bilirubin levels in the HDivIG group were lower despite reduced frequency of exchange transfusions. No side effects of HDivIG treatment were observed. We conclude that HDivIG therapy by a yet unknown mechanism reduces serum bilirubin levels and the need for blood exchange transfusions in children with Rh hemolytic disease. Rhesus haemolytic disease is a continuing problem in the newborn especially in countries where the use of anti-D immunoglobulin is not prevalent. The fetuses may need intrauterine transfusions to prevent hydrops faetalis and they also may need exchange transfusions to treat the hyperbilirubinaemia that develops after birth. These interventions expose the baby to several blood donors, hence the risk of infection and exchange transfusions. This study was performed to test whether the use of high-dose intravenous immunoglobulin soon after the birth of these infants reduced the need for exchange transfusions. After randomization, intravenous immunoglobulin was given at a dose of 500 mg/kg to 22 infants in the treatment group. Nothing was given to the 19 controls. The number of exchange transfusions needed decreased significantly in the treatment group. No side-effects of intravenous immunoglobulins were seen. The effectiveness of early single volume exchange transfusion (ET; 80 ml/kg) was compared with that of early double volume exchange transfusion (160 ml/kg) for treatment of hemolytic disease of the newborn caused by AB0 incompatibility. Twenty full-term infants with AB0 hemolytic disease were randomized into the two treatment groups. The groups were comparable for gestational age, body weight, hemoglobin values, reticulocyte count, maximum serum bilirubin levels, rate of rise of serum bilirubin before ET, antibody titer, and age at time of ET (all p greater than 0.05). The efficacy of treatment was similar in both groups taking into account the mean bilirubin level after ET, post-ET bilirubin, duration of phototherapy following ET, and frequency of second ET (all p greater than 0.05). However, platelet count immediately after ET was lower in the double volume ET group as compared to the single volume ET group (p less than 0.01). Hemoglobin values immediately after ET were higher in the double volume ET group (p less than 0.01). At ten days of life no differences were detectable. The results of this study indicate that the effectiveness of single volume ET for treatment of full-term infants with jaundice due to AB0 incompatibility is at least comparable to that of double exchange ET. Furthermore, the lesser aggressive approach determines less complications such as a decrease of platelet count. Previous studies have shown a benefit of intravenous immunoglobulin infusions for the prophylaxis of primary CMV infections in renal transplant recipients. This study was undertaken in order to see if high-risk renal transplant patients at risk for secondary CMV infection would benefit from prophylactic intravenous immunoglobulin infusions. A randomized prospective study of renal transplant recipients who were considered at high risk for secondary CMV infection was performed. Thirty-four patients were studied, 16 receiving the intravenous immunoglobulin infusions and 18 being untreated controls. Unselected lots of Sandoglobulin (Sandoz) were used for the treatment group (500 mg/kg x 3 doses, followed by 250 mg/kg x 2 doses at 2-week intervals). The number of days febrile and days hospitalized secondary to CMV illness, and the number of complications secondary to CMV illness, were significantly reduced in the patients who were prophylactically treated with intravenous immunoglobulin infusions. None of the patients died from CMV infection in either group. There were no significant complications related to the intravenous immunoglobulin infusions. This study suggests that prophylactic immunoglobulin infusions will reduce the severity of CMV infection in the patient who is at risk for secondary or reactivation infection as well as the patient at risk for primary infection. This therapy should be considered for renal transplant recipients who are at high risk for developing CMV infection, both primary and secondary. We prospectively studied newborn infants with sepsis and neutropenia who were randomly selected to receive standard supportive care and either adjuvant granulocyte transfusions or intravenous immune globulin (IVIG) infusions; 21 infants received granulocyte transfusions and 14 received IVIG infusions. Half of the patients were premature (gestational age less than or equal to 32 weeks); the average postnatal age was 5 days (range 3 to 8 days). All infants had neutropenia by the criteria of Manroe et al., and the mean average bone marrow neutrophil storage pool ranged between 35% and 37%. There were no significant differences with respect to serum IgG, IgA, IgM, and total hemolytic complement values between treatment groups or between survivors and nonsurvivors. Clinical severity as defined by hypoxia, acidosis, and hypotension was similar between treatment groups. Group B streptococcus was the most common organism identified and accounted for almost 33% of all bacterial isolates. There was a significantly different survival rate in the group receiving polymorphonuclear leukocyte transfusions (100%, 21/21) compared with the group receiving IVIG infusions (64%, 9/14; p = less than 0.03). There were no significant complications in either treatment group with respect to fluid overload, secondary infection, blood group sensitization, pulmonary complications, or graft-versus-host disease. This pilot study suggests a possible benefit of granulocyte transfusions compared with 'IVIG therapy in the adjuvant treatment of neonatal neutropenia and overwhelming bacterial sepsis. This study was designed to test the hypothesis that administration of immune globulin to human neonates with early-onset bacterial sepsis would (1) facilitate neutrophil egress from the marrow, (2) improve serum opsonic capacity, and (3) facilitate recovery from the infectious illness. Twenty-two newborn infants with clinical signs of early-onset sepsis were given an intravenous infusion of either 750 mg of immune globulin (IVIG) per kilogram of body weight or the same volume of a vehicle control (albumin). All 22 infants survived, but significant hematologic, immunologic, and respiratory differences were observed after the IVIG and not after the control infusion. Eleven of the patients had neutropenia; 24 hours after the infusions, the neutropenia had resolved in all six IVIG recipients but persisted in all five control recipients (p less than 0.001). Ten patients had I/T neutrophil ratios (a measure of immature neutrophils to total neutrophils on the leukocyte differential count) of less than 0.2. One hour after completion of the infusions, all five IVIG recipients had elevated I/T ratios (mean +/- SEM:0.10 +/- 0.05 before vs 0.43 +/- 0.03 after infusion; p less than 0.001), suggesting a prompt release of neutrophils from the marrow neutrophil storage pool into the circulation; no increase in the I/T ratio was observed in the control recipients. Six hours after the IVIG infusions, the ratio of arterial oxygen tension to fraction of inspired oxygen increased; no increase was observed after control infusions. Serum concentrations of IgG, IgG1, IgG2, IgG3, IgG4, and total hemolytic complement and the capacity of serum to support opsonophagocytosis of type II and type III group B streptococci increased markedly in the IVIG recipients but not in the control subjects. We conclude that administration of 750 mg IVIG per kilogram to neonates with clinical signs of early-onset sepsis was associated with immunologic, hematologic, and physiologic improvement. Thirty-seven neonates with confirmed septicemia through hemoculture were studied. Of them, 18 were treated with antibiotic and the other 19 were given 500 mg/kg of intravenous immunoglobin with a pH of 4.25 (IGIV). The greater part of the neonates in this study were full-term or near full-term. There were no differences in age, gestational age and weight, nor in mortality, the bacterias found and the clinical manifestations which were seen in both groups. Yet, the hospitalary stay was shorter for those in the group treated with IGIV (13.9 +/- 5.7 days) than in the trial group (24.4 +/- 10.3 days); as well as some clinical manifestations like diarrhea and splenomegalia (P < 0.05). The serum of the neonates from the IGIV group showed a greater capacity of opsonization and inhibition of bacterial growth than those in the trial group (P < 0.001), coinciding with an increase of 300 mg/dL in the serum levels of IgG of the group treated with IGIV from the 3rd day of the study and the C4 and B-Properdine factor serum levels from the 7th day of the study, while in the trial group, there were no changes in these factors (P < 0.001). Even though no differences were seen in the mortality rate due to septicemia, the results suggest a much shorter evolution of the illness in patients treated with IGIV. In addition, the serum of those patients treated with IGIV showed in in vitro studies, a better bacteriostatic activity and a better capacity to opsonize the bacterias isolated in the hemocultures.(ABSTRACT TRUNCATED AT 250 WORDS) 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.
                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.
                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).
                Passive immunotherapy with intravenous immunoglobulin decreases the risk of acute GVHD, associated interstitial pneumonia, and infections after bone marrow transplantation.
Although the results show a significant reduction in the need for exchange transfusion in those treated with intravenous immunoglobulin, the applicability of the results is limited. The number of studies and infants included is small and none of the three included studies was of high quality. The protocols of two of the studies mandated the use of early exchange transfusion, limiting the generalizability of the results. Further well designed studies are needed before routine use of intravenous immunoglobulin can be recommended for the treatment of isoimmune haemolytic jaundice.