Recovery of IgG Production Following Rituximab Therapy after Allogeneic Stem Cell Transplantation

Rituximab is a monoclonal antibody to the CD20 antigen expressed on B lymphocytes. Several recent reports suggest that rituximab may be used to treat complications of SCT including GVHD and EBV reactivation. The long term consequences on IgG recovery aren’t well studied. This is a retrospective analysis of allogeneic pediatric SCT patients treated with rituximab at Loma Linda University from 2004 to 2013. We treated 23 patients with rituximab following allogeneic SCT (11 MUD, 7 MSD, 3 Cord) for post-transplant EBV reactivation alone (4), cGVHD alone (4), cGVHD in combination with thrombocytopenia (9), plus hemolysis (4) and EBV reactivation (2). Most patients required IVIG monthly (18) or more frequently (4) to maintain serum IgG levels >500mg/dl. We examined the length of time from end of rituximab therapy to recovery of endogenous IgG production. The effect on recovery of IgG production of cGVHD therapy, EBV infection, age, type of stem cell graft, and number of doses of rituximab were evaluated. Those treated for cGVHD plus any other indication (n=19) received a median of 11 doses of rituximab (range 4 to >30). Among these patients 11 of 14 whose cGVHD resolved and came off immune suppression recovered the ability to produce IgG completely (9) or partially (2, defined as decreasing frequency of IVIG infusions to maintain IgG>500mg/dl). Median time to recovery was 14 months (range 1-50 months) after last dose of rituximab. For patients who continued to require immune suppression for cGVHD only 1 of 5 recovered IgG production 13 months after last dose of rituximab. The remaining 4 patients required monthly or greater IVIG for >3 years after the last dose of rituximab (all still requiring IVIG). There were 4 patients treated with 2-4 doses of rituximab for EBV reactivation early after SCT, and 1 treated with 11 doses for cGVHD and EBV. Only 1 of these 5 has completely recovered IgG production. The 4 other patients remain dependent on IVIG a median of >39 months since end of rituximab therapy.

We found no relationship between age of patient or duration of rituximab therapy on the time interval between end of rituximab therapy and onset of endogenous IgG production. Recipients of MUD grafts had a non-significant increase in failure to recover endogenous IgG production, but when the impact of therapy for cGVHD was taken into account the type of stem cell graft lost significance.

Ability to recover endogenous IgG production following treatment with rituximab after SCT depends on successful treatment of cGVHD and in this group of patients requires about 1 year from end of therapy. Among those treated with rituximab whose cGVHD does not resolve and in those with early EBV reactivation, loss of IgG production persists at least several years, and this may be unrelated to rituximab therapy.