Personalized Therapeutic Use of Intravenous Immunoglobulin in Heart Recipients with Severe Infections and IgG Hypogammaglobulinemia: Impact on Clinical Outcomes

PurposeInfections are the first cause of death between 1 month and 1 year after heart transplantation (HT). Post-HT IgG hypogammaglobulinemia (HGG) is frequent after HT and a risk factor of severe infection. This risk factor can be reconstituted. It has been suggested that a biological IgG level is that obtained until symptoms of infection are controlled. We evaluated the impact of therapeutic use of intravenous immunoglobulin (IVIG) in heart recipients with severe infections and HGG on clinical outcomes.MethodsA retrospective study of 197 heart recipients in a single center. Inclusion criteria: Survival of at least one month, use of induction therapy with monoclonal antibodies. Exclusion criteria: Use of IVIG before HT. During this period 71 patients that developed severe post HT infections and who were found to have HGG (serum IgG<600 mg/dL), received non-specific IVIG (Flebogamma 5%) in addition to conventional antimicrobial therapy. The the aim was contributing to control of infection. Monthly doses of 300-400 mg/kg were administered up to three months after infections were resolved (negative bacterial culture or CMV antigenemia). 126 heart recipients from the same center, who where not treated with IVIG, were analyzed as controls. Clinical data were prospectively collected during routine visits without loss of follow-up.ResultsBoth groups were comparable in terms of demographic and clinical variables (age, sex, pre-HT infections, diabetes, renal failure, CMV serological status; ischemia time and extracorporeal circulation time; type of induction and maintenance therapy; antimicrobial prophylaxis; prevalence of primary allograft failure. IVIG group tended to have a lower rate of neoplasia (4 vs 9%, p=0.14). IVIG treated recipients disclosed a lower rate of death (8.5% vs 22.2%, p=0.018). In multivariate regression analysis, IVIG use (RH 0.28, 95%CI 0.10-0.75, p=0.011) and use of non-cytolitic induction (anti-25) vs cytolitic (ATG) (RH 0.22, 95%CI 0.09-0.50, p=0.0003) remained in the final model as protective factors.ConclusionPersonalized immunemodulation of HGG in heart recipients with severe infections is associated with better outcome. The efficacy of this IVIG indication in solid organ transplantation warrants further evaluation in a multicenter randomized clinical trial. PurposeInfections are the first cause of death between 1 month and 1 year after heart transplantation (HT). Post-HT IgG hypogammaglobulinemia (HGG) is frequent after HT and a risk factor of severe infection. This risk factor can be reconstituted. It has been suggested that a biological IgG level is that obtained until symptoms of infection are controlled. We evaluated the impact of therapeutic use of intravenous immunoglobulin (IVIG) in heart recipients with severe infections and HGG on clinical outcomes. Infections are the first cause of death between 1 month and 1 year after heart transplantation (HT). Post-HT IgG hypogammaglobulinemia (HGG) is frequent after HT and a risk factor of severe infection. This risk factor can be reconstituted. It has been suggested that a biological IgG level is that obtained until symptoms of infection are controlled. We evaluated the impact of therapeutic use of intravenous immunoglobulin (IVIG) in heart recipients with severe infections and HGG on clinical outcomes. MethodsA retrospective study of 197 heart recipients in a single center. Inclusion criteria: Survival of at least one month, use of induction therapy with monoclonal antibodies. Exclusion criteria: Use of IVIG before HT. During this period 71 patients that developed severe post HT infections and who were found to have HGG (serum IgG<600 mg/dL), received non-specific IVIG (Flebogamma 5%) in addition to conventional antimicrobial therapy. The the aim was contributing to control of infection. Monthly doses of 300-400 mg/kg were administered up to three months after infections were resolved (negative bacterial culture or CMV antigenemia). 126 heart recipients from the same center, who where not treated with IVIG, were analyzed as controls. Clinical data were prospectively collected during routine visits without loss of follow-up. A retrospective study of 197 heart recipients in a single center. Inclusion criteria: Survival of at least one month, use of induction therapy with monoclonal antibodies. Exclusion criteria: Use of IVIG before HT. During this period 71 patients that developed severe post HT infections and who were found to have HGG (serum IgG<600 mg/dL), received non-specific IVIG (Flebogamma 5%) in addition to conventional antimicrobial therapy. The the aim was contributing to control of infection. Monthly doses of 300-400 mg/kg were administered up to three months after infections were resolved (negative bacterial culture or CMV antigenemia). 126 heart recipients from the same center, who where not treated with IVIG, were analyzed as controls. Clinical data were prospectively collected during routine visits without loss of follow-up. ResultsBoth groups were comparable in terms of demographic and clinical variables (age, sex, pre-HT infections, diabetes, renal failure, CMV serological status; ischemia time and extracorporeal circulation time; type of induction and maintenance therapy; antimicrobial prophylaxis; prevalence of primary allograft failure. IVIG group tended to have a lower rate of neoplasia (4 vs 9%, p=0.14). IVIG treated recipients disclosed a lower rate of death (8.5% vs 22.2%, p=0.018). In multivariate regression analysis, IVIG use (RH 0.28, 95%CI 0.10-0.75, p=0.011) and use of non-cytolitic induction (anti-25) vs cytolitic (ATG) (RH 0.22, 95%CI 0.09-0.50, p=0.0003) remained in the final model as protective factors. Both groups were comparable in terms of demographic and clinical variables (age, sex, pre-HT infections, diabetes, renal failure, CMV serological status; ischemia time and extracorporeal circulation time; type of induction and maintenance therapy; antimicrobial prophylaxis; prevalence of primary allograft failure. IVIG group tended to have a lower rate of neoplasia (4 vs 9%, p=0.14). IVIG treated recipients disclosed a lower rate of death (8.5% vs 22.2%, p=0.018). In multivariate regression analysis, IVIG use (RH 0.28, 95%CI 0.10-0.75, p=0.011) and use of non-cytolitic induction (anti-25) vs cytolitic (ATG) (RH 0.22, 95%CI 0.09-0.50, p=0.0003) remained in the final model as protective factors. ConclusionPersonalized immunemodulation of HGG in heart recipients with severe infections is associated with better outcome. The efficacy of this IVIG indication in solid organ transplantation warrants further evaluation in a multicenter randomized clinical trial. Personalized immunemodulation of HGG in heart recipients with severe infections is associated with better outcome. The efficacy of this IVIG indication in solid organ transplantation warrants further evaluation in a multicenter randomized clinical trial.