Incidence and Risk Factors for Hypogammaglobulinemia in Pediatric Allogeneic Stem Cell Transplant (SCT) Patients

Impairment of antibody immunity correlates with an increased risk of infections after SCT primarily due to encapsulated bacteria. Patients with hypogammaglobulinemia are more prone to recurrent infections that can potentially be fatal. The incidence of this complication is not well known in children following allogeneic SCT. We sought to evaluate the incidence and risk factors of this complication in pediatric recipients of allogeneic SCT.

All patients receiving allogeneic SCT at Vanderbilt Children's Hospital between 1999 and 2011 were included in this analysis. Excluded were patients with primary immune deficiency. IgG levels were measured every 2 weeks following SCT for the first 100 days and then monthly thereafter. Hypogammaglobulinemia was defined as IgG<500 mg/dL. All patients with hypogammaglobulinemia received IVIG replacement therapy. Detailed patient and outcome characteristics were recorded.

A total of 177 patients with a median age of 9 years were included in this analysis. 137 (77%) had malignant diseases and 108 (61%) received cells from an unrelated source. Bone marrow was the stem cell source in 120 (68%) while 30 (17%) received PBSC and 27 (15%) received cord blood. 137 of 177 (77.4%) patients developed hypogammaglobulinemia at a median of 69 days (range 5–339) after transplant. In multivariable analysis patients who developed hypogammaglobulinemia were significantly younger HR=1.05 (95% CI, 1.02–1.1, p=0.002), have malignant disease: HR=2.73: (95% CI:1.6–4.7,p<0.001), received unrelated donor transplant: HR=2.78 (95% CI: 1.75–5.0, p<0.001) and developed acute GVHD: HR=2.24 (95% CI: 1.50–3.32, p<0.001). Patients who developed chronic GVHD and survived for more than 1 year post-transplant were more likely to still be receiving IVIG replacement for hypogammaglobulinemia, (HR=115.5, 95% CI: 14.58–914.1, p<0.001). All patients who are alive >1 year post transplant and are off immune suppression have normal IgG levels and are not requiring replacement therapy.

Hypogammaglobulinemia is a common complication in pediatric patients following allogeneic SCT. Younger patients, those with malignant diseases and recipients of unrelated donor SCT are at higher risk. Acute and chronic GVHD increased the risk of developing hypogammaglobulinemia. Close monitoring of IgG level should be considered in those at highest risk.

No relevant conflicts of interest to declare.