title: Serum interleukin-3 levels following autologous or allogeneic bone marrow transplantation: effects of T-cell depletion, blood stem cell infusion, and hematopoietic growth factor treatment.
abstract: Engraftment of marrow following autologous or allogeneic bone marrow transplantation (BMT) may be influenced by quantity and function of stem cells. T lymphocytes, supporting microenvironmental cells, and hematopoietic growth factors (HGF). To elucidate the physiologic role of interleukin-3 (IL-3) in the engraftment process, serum IL-3 levels were measured in over 400 samples from 77 transplant recipients before and for up to 3 weeks following transplantation using a novel enzyme-linked immunoabsorbent assay (ELISA) with a sensitivity of > or = 78 pg/mL. Thirty-seven patients received two to three log T-cell-depleted allografts. In the remaining 40 patients (18 autologous marrow, 12 allogeneic marrow, and 10 autologous peripheral blood [PB] stem cell), T cells were not depleted (non-TCD) from the grafts. A burst of IL-3 (peak levels, 1,500 to 6,000 pg/mL) was detected in the immediate posttransplant period between day 0 and day 14 in all non-TCD recipients and in 21 of 37 (57%) of TCD recipients. A strong inverse relationship between IL-3 levels and absolute neutrophil count (ANC) was observed in both non-TCD recipients (r = -.796) and in TCD recipients (r = -.897). However, both peak IL-3 levels and mean IL-3 levels from day 0 through 14 were significantly lower in TCD recipients compared with either autologous or unmodified allogeneic marrow recipients (P < .01). The lowest peak or mean day 0 through 14 IL-3 levels were observed in matched related recipients undergoing the most aggressive (2.5 to 3.0 log) T-cell-depleted BMT. Autografted patients receiving blood stem cell transplants alone or posttransplant granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage colony stimulating factor (GM-CSF) also had significantly lower peak IL-3 levels (P < .01). In patients receiving TCD grafts, administration of antithymocyte globulin (ATG) posttransplant significantly increased peak IL-3 levels compared with patients not treated with ATG (P < .04). This study shows that endogenous release of IL-3 is strongly associated with myeloid engraftment and inversely related to ANC. Removal of T lymphocytes from donor marrow or acceleration of engraftment by use of stem cells or growth factors appears to blunt the endogenous release of IL-3 whereas use of ATG posttransplant increases IL-3 release.
authors.affiliation: Department of Medicine, Temple University School of Medicine, Philadelphia, PA.
authors.forename: K F
authors.initials: KF
authors.lastname: Mangan
authors.forename: M T
authors.initials: MT
authors.lastname: Mullaney
authors.forename: T D
authors.initials: TD
authors.lastname: Barrientos
authors.forename: N A
authors.initials: NA
authors.lastname: Kernan
mesh_terms: D000293:Adolescent; D000328:Adult; D016026:Bone Marrow Transplantation; D003429:Cross Reactions; D004797:Enzyme-Linked Immunosorbent Assay; D016298:Hematopoietic Cell Growth Factors / Q000627:therapeutic use*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007377:Interleukin-3 / Q000097:blood*; D008212:Lymphocyte Depletion; D008875:Middle Aged; D013601:T-Lymphocytes / Q000502:physiology*; D014182:Transplantation, Autologous; D014184:Transplantation, Homologous
chemical_list: D016298:Hematopoietic Cell Growth Factors; D007377:Interleukin-3