Immune reconstitution after T-cell replete HLA haploidentical hematopoieticstem cell transplantation using high-dose post-transplant cyclophosphamide

摘要

As HLA haploidentical related donors are quickly available, HLAhaploidentical hematopoietic stem cell transplantation (haploHSCT) using high-dosepost-transplant cyclophosphamide (PTCy) is now widely used. Recent basic andclinical studies revealed the details of immune reconstitution after T-cell repletehaploHSCT using PTCy. T cells and NK cells in the graft proliferate abundantly at day 3post-haploHSCT, and the PTCy eliminates these proliferating cells. After ablation ofproliferating mature cells, donor-derived NK cell reconstitution occurs after the secondweek; however, recovering NK cells remain functionally impaired for at least severalmonths after haploHSCT. PTCy depletes proliferating cells, resulting in the preferentialaccumulation of Treg and CD4+ T cells, especially the memory stem T cell(TSCM) phenotype. TSCM capable of bothself-renewal and differentiation into effector T cells may play an important role in thefirst month of immune reconstitution. Subsequently, de novo T cellsprogressively recover but their levels remain well below those of donor CD4+ T cells atthe first year after haploHSCT. The phenotype of recovering T cells after HSCT ispredominantly effector memory, whereas B cells are predominantly phenotypically naivethroughout the first year after haploHSCT. B cell recovery depends on denovo generation and they are not detected until week 4 after haploHSCT. At week5, recovering B cells mostly exhibit an unconventional transitional cell phenotype and thecell subset undergoes maturation. Recent advances in immune reconstitution have improvedour understanding of the relationship between haploHSCT with PTCy and the clinicaloutcome.