Immunohematological reconstitution in pediatric patients after T-cell-depleted HLA-haploidentical stem cell transplantation for thalassemia

To analyze immunohematologic reconstitution, particularly of natural killer (NK) cells, we evaluated 13 bthalassemia patients after 20 and 60 days and 1 year posttransplantation with T cell-depleted HLA-haploidentical stem cells. We assessed lymphocyte and bone marrow (BM) progenitor cell phenotype and differentiation capacity, spontaneous BM cytokine production, stromal cells, and stromal cell interleukin (IL)-7 production. A reduced clonogenic capability manifested at day 120. Patients had significantly lower CD41 T cells versus controls, mainly in the CD45RA1CD62L1 subset. NKs were among the first lymphocytes to repopulate the peripheral blood. At day 160, an increase in primitive BM progenitor cells paralleled small increases in CD41, naı¨ve CD41, and thymic naı¨ve Th cells. A significant increase in CD41 and CD81 markers paralleled an increase in CD32CD161 NKs, especially with full engraftment. In patients with stable mixed chimerism we observed very low levels of CD31 donor chimerism early after transplant that increased over time, but a stable population of high donor NK cells, suggesting a role of these cells on donor engraftment. Stromal cells secreted less IL-7 and displayed ‘‘macrophage-like’’ morphology. Patients initially manifested impaired stem/progenitor cell growth and differentiation capacity in parallel with altered T cell homeostasis and a reduced T cell naı¨ve compartment. We hypothesize that T cell compartment damage partly arises from altered new T cell production from the hematopoietic stem/progenitor cells under stromal cytokine influence. NNK subset analysis might be useful for determining transplant outcome.