In the setting of
hematopoietic stem cell transplantation (HSCT),
Rituximab (RTX) is used for the treatment and prevention of EBV-associated post-
transplantation lymphoproliferative disease or autoimmune phenomena such as
autoimmune hemolytic anemia (AIHA). Persistent
hypogammaglobulinemia and
immunoglobulin substitution dependence has been observed in several patients after RTX treatment despite the normalization of total B cell numbers. We aimed to study whether this is a B cell intrinsic phenomenon. We analyzed four patients with different primary diseases who were treated with myeloablative conditioning and matched unrelated donor HSCT who developed persistent
hypogammaglobulinemia after receiving RTX treatment. They all received RTX early after HSCT to treat
EBV infection or AIHA post-HSCT. All patients showed normalized total B cell numbers but absent to very low
IgG positive memory B cells, and three lacked
IgA positive memory B cells. All of the patients had full donor chimerism, and none had encountered
graft-versus-host disease. Sorted peripheral blood naïve B cells from these patients, when stimulated with
CD40L,
IL21,
IL10 and
anti-IgM, demonstrated intact B cell differentiation including the formation of class-switched memory B cells and
IgA and
IgG production. Peripheral blood T cell numbers including CD4 follicular T-helper (Tfh) cells were all within the normal reference range. In conclusion, in these four HSCT patients, the persistent
hypogammaglobulinemia observed after RTX cannot be attributed to an acquired intrinsic B cell problem nor to a reduction in Tfh cell numbers.