Allogeneic transplantation of peripheral blood stem cell grafts results in a massive decrease of primitive hematopoietic progenitor frequencies in reconstituted bone marrows

摘要

The success of allogeneic hematopoietic stem cell transplantation (alloSCT) is indicated by the reconstitution of the peripheral blood system of patients after alloSCT and the engraftment of hematopoietic stem and progenitor cells (HSPCs) into their bone marrow (BM). The number of CD34(+) cells is commonly used as surrogate for the content of hematopoietic stem cells in the grafts. During the last decade, several antigens (including CD133, CD45RA, CD38, and CD10) were identified allowing discrimination of different HSPC subpopulations within the human CD34(+) cell compartment. Although such studies increased our understanding of early human hematopoiesis tremendously, hardly any study dissected the CD34(+) compartment in the alloSCT setting. Consequently, we comprehensively analyzed the CD34(+) compartment in G-CSF-stimulated peripheral blood stem cell grafts of allogeneic donors, in BM samples of the respective recipients 4 weeks after alloSCT, and in BM samples of healthy donors. We demonstrate that alloSCT is associated with a dramatic shift from primitive to more mature HSPC types. Upon investigating whether the composition of engrafted CD34(+) cells has any impact on the incidence and severity of graft-versus-host disease, we did not find any correlation. However, more detailed analyses of the CD34(+) compartment may elucidate associations with other transplantation-related complications.