Postgrafting administration of granulocyte colony-stimulating factor impairs functional immune recovery in recipients of human leukocyte antigen haplotype-mismatched hematopoietic transplants

In human leukocyte antigen haplotype-mismatched transplantation, extensive T-cell depletion prevents graft-versus-host disease (GVHD) but delays immun e recovery. Granulocyte colony-stimulating factor (G-CSF) is given to donor s to mobilize stem cells and to recipients to ensure engraftment. Studies h ave shown that G-CSF promotes T-helper (Th)-2 immune deviation which, unlik e Th1 responses, does not protect against intracellular pathogens and fungi . The effect of administration of G-CSF to recipients of mismatched hematop oietic transplants with respect to transplantation outcome and functional i mmune recovery was investigated. In 43 patients with acute leukemia who rec eived G-CSF after transplantation, the engraftment rate was 95%. However, t he patients had a long-lasting type 2 immune reactivity, ie, Th2-inducing d endritic cells not producing interleukin 12 (IL-12) and high frequencies of IL-4- and IL-10-producing CD4(+) cells not expressing the IL-12 receptor b eta (2) chain. Similar immune reactivity patterns were observed on exposure of donor cells to G-CSF. Elimination of postgrafting administration of G-C SF in a subsequent series of 36 patients with acute leukemia, while not adv ersely affecting engraftment rate (93%), resulted in the anticipated appear ance of IL-12-producing dendritic cells (1-3 months after transplantation v ersus > 12 months in transplant recipients given G-CSF), of CD4+ cells of a mixed Th0/Th1 phenotype, and of antifungal T-cell reactivity in vitro. Mor eover, CD4+ cell counts increased in significantly less time. Finally, elim ination of G-CSF-mediated immune suppression did not significantly increase the incidence of GVHD (< 15%). Thus, this study found that administration of G-CSF to recipients of T-cell-depleted hematopoietic transplants was ass ociated with abnormal antigen-presenting cell functions and T-cell reactivi ty. Elimination of postgrafting administration of G-CSF prevented immune dy sregulation and accelerated functional immune recovery. (Blood. 2001;97:251 4-2521) (C) 2001 by The American Society of Hematology.