Syngeneic transplantation with peripheral blood mononuclear cells collected after the administration of recombinant human granulocyte colony-stimulating factor

Abstract

Five syngeneic transplants were performed in four patients following myeloablative therapy using unmodified peripheral blood mononuclear cells (PBMCs) collected after the administration of recombinant human granulocyte colony stimulating factor (rhG-CSF) to normal donors. The only toxicity experienced by the four normal donors was bone pain. Four patients received two collections of PBMCs, and a second transplant was performed in one patient with one collection. The patients received a median of 20.53 x 10(8) total nucleated cells/kg (range 20 to 25.5), 11.3 x 10(8) total mononuclear cells/kg (range 6.52 to 17.2), 113.1 x 10(4)/kg CFU-GM (range 46.7 to 211.8) and 9.6 x 10(6) CD34+ cells/kg (range 1.6 to 12.6) Post-transplant growth factors were not administered. The median time to an absolute neutrophil count greater than 0.5 x 10(9)/L was 14 days (range 10 to 18). The median time to platelet transfusion independence was 11 days (range 10 to 13). Two patients had the number of CD3+ T lymphocytes determined in the pheresis product. An average of 3.04 x 10(10) CD3+ cells were collected per pheresis. This represents an approximate 1 log increase over the number of T lymphocytes in a typical bone marrow transplant. Rh-GCSF can be used to mobilize peripheral blood progenitor cells from normal donors with minimal toxicity. Studies of allogeneic transplants using PBMCs collected after rhG-CSF administration to determine permanent grafting ability and the incidence and severity of graft-versus-host disease are warranted.

The Use of Mobilized Peripheral Blood Stem Cells from Normal Donors for Allografting

“…After three days of rHuG-CSF treatment, the WBC, polymorphonuclear, and lymphocyte concentrations in the donor's PB exceeded baseline by 6.4-, 8.0and 2.2-fold, respectively [5]. A similar increase of T lymphocytes by day 3 of 16 µg/kg/d rHuG-CSF has been reported by Weaver et al [11], namely 1.5 to 2.0 times over baseline. On the other hand, PB CD34 + cells and primitive subsets such as CD34 + Thy-1 dim , and CD34 + Thy-1 dim CD38cells increased by 16.3-fold, 24.2-fold and 23.2-fold, respectively, suggesting a selective peripheralization effect of rHuG-CSF on hematopoietic progenitor cells and, in particular, on their more primitive stem cell subsets [5].…”

Allogeneic bone marrow transplantation with T‐cell‐depleted marrow grafts for patients with poor‐risk relapsed low‐grade non‐Hodgkin's lymphoma

“…These data support the concept of an impaired immune status of patients with low-grade NHL, therefore predisposing to development of GvHD despite T-cell depletion of the marrow grafts. This conclusion may have consequences for future allogeneic transplantation programmes since stem cells derived from peripheral blood instead of bone marrow are increasingly used and are known to contain higher numbers of T lymphocytes, representing effector cells of GvHD (Dreger et al, 1994;Weaver et al, 1994). However, until now no increase in GvHD has been reported in patients transplanted with unmanipulated peripheral blood derived stem cell grafts compared to bone marrow derived stem cell grafts (Bensinger et al, 1996;Pavletic et al, 1997).…”

Granulocyte colony‐stimulating factor has a negative effect on stroke outcome in a murine model

“…Granulocyte colony-stimulating factor (G-CSF) was identified in 1975 and has been broadly used for mobilizing granulocytes from bone marrow (Weaver et al, 1993). G-CSF is also known to mobilize immature hematopoietic cells that include endothelial progenitor cells (EPCs) (Willing et al, 2003).…”