Immune reconstitution after hematopoietic stem cell transplantation with reduced intensity conditioning for inborn errors of immunity

Abstract

Abstract Purpose Hematopoietic stem cell transplantation (HSCT) is the only curative treatment for many inborn errors of immunity (IEI). Reduced-intensity conditioning (RIC) is used in this setting because of low mortality and morbidity. However, the timely reconstitution of the immune system is essential for long-term survival. Methods We included forty-one IEI patients transplanted from September 2016 to September 2019 using fludarabine-based RIC protocol. Lymphocyte reconstitution was evaluated by flow cytometry of CD3, CD4, and CD8 for T lymphocytes, CD19 for B lymphocytes, and CD56 for NK cells in + 3, +6, + 9, and + 12 months after HSCT. We analyzed the effect of different factors on the duration of immune cell reconstitution. Results By the third month, 68% of total T cells and 78% of NK cells had returned to normal. However, 73% of B cells, 29% of CD4+ T cells, and 83% of CD8+ T cells were normalized 12 months after HSCT. The absence of acute graft-versus-host disease (aGVHD) was associated with earlier CD3+ T cell and B cell recovery. Absence of chronic GVHD (cGVHD) and cytomegalovirus (CMV) infection was associated with early CD4+ T cell recovery. Conclusion With the fludarabine-based RIC protocol, CD4+ T cells showed slow and poor recovery during follow-up. However, this poor recovery did not lead to increased rates of infections. In addition, CMV infection and the development of acute and chronic GVHD negatively affected immune cell recovery. Using an appropriate GVHD prophylaxis regimen and adequate treatment of CMV may improve the immune reconstitution post-HSCT.