Dosing Subcutaneous Immunoglobulin to Achieve Target Levels in Hematopoietic Cell Transplant Recipients

Secondary hypogammaglobulinemia (SHG) is a frequent complication after hematopoietic cell transplantation (HCT), especially allogeneic HCT, and predisposes to recurrent or severe infections. Immunoglobulin replacement therapy (IgRT) is commonly used, but the dose-response relationship between subcutaneous IgRT (ScIgRT) and serum IgG levels after HCT remains insufficiently defined. We assessed the association between ScIgRT dose and short-term changes in IgG. We performed a single-center retrospective cohort study of patients who initiated ScIgRT ≥ 60 days after autologous or allogeneic HCT (2017-2023). Eligibility required IgG measurement within 1 week before and 1 month (±1 week) after initiation; patients who received intravenous IgRT within 1 month or had active relapse/progression were excluded. Change in IgG was compared using the Mann-Whitney U test, and dose-response was evaluated with Pearson correlation (two-sided p < 0.05). Eighty-one patients met criteria (median age, 57 years [19-75]; 73 [90.1%] allogeneic). ScIgRT was initiated a median of 124 days after HCT. Median IgG increased from 669 to 780 mg/dL at 1 month (p < 0.01). Monthly ScIgRT dose correlated with the magnitude of IgG rise (r=0.51, p < 0.01). Doses ≥ 24 g/month produced greater median increases than < 24 g/month (163 vs. 59 mg/dL, p < 0.01). Higher ScIgRT dosing was associated with larger short-term increases in IgG among HCT recipients with SHG. These findings support dose optimization to achieve target IgG troughs and justify prospective studies to determine whether maintaining higher IgG levels reduces infections and improves post-transplant outcomes.