Immune Reconstitution In Fanconi Anemia Patients Following Allogeneic Bone Marrow Transplantation

Fanconi anemia is an autosomal recessive or X-linked genetic disorder characterized by bone marrow (BM) failure/aplasia. Failure of hematopoiesis results in depletion of the BM stem cell reservoir, which leads to severe anemia, neutropenia and thrombocytopenia, frequently requiring therapeutic interventions including hematopoietic stem cell transplantation (HSCT). Successful BMT requires reconstitution of normal immunity.

In the present study, we performed a detailed analysis of the distribution of peripheral blood subsets of T, B and NK lymphocytes in 23 patients with Fanconi anemia before and after BM transplantation (at days D+30, D+60 and D+100, D+180 D+270 and D+360). In parallel, we also compared the patients groups who received related and unrelated bone marrow, pre and one year after BMT.

After transplantation, we found different kinetics of recovery for the distinct major lymphocyte subsets. NK cells were the first to recover, followed by cytotoxic CD8⁺ T-cells and B-cells, and finally also the CD4⁺ T-helper cells. Early recovery was at the expenses of memory cells which would therefore be potentially derived from the graft whereas, recent thymic emigrant (CD31⁺ CD45RA⁺) and naive CD4⁺ or CD8⁺ T-cells, rose only 6 months after HSCT, in the presence of immunosuppressive graft-vs-host disease (GVHD) prophylactic agents. While only slight differences were observed in the early recovery of cytotoxic CD8⁺ T-cells among cases receiving a graft from related vs. unrelated donors, cases suffering from GVHD displayed more marked differences vsother patients.

Overall, our results support the utility of post-transplant monitoring of peripheral blood lymphoid subsets, for improved monitoring and follow-up of Fanconi anemia patients undergoing BMT.

No relevant conflicts of interest to declare.