T cell-depleted granulocyte colony-stimulating factor (G-CSF) modified allogeneic bone marrow transplantation for hematological malignancy improves graft CD34⁺ cell content but is associated with delayed pancytopenia

Abstract

To increase the stem cell content of T cell-depleted bone marrow transplants (BMT), we treated 12 patients with hematological malignancies with BMT from HLA-identical sibling donors given G-CSF 10 μg/kg/day for 5 days before marrow harvest. After CD34⁺ cell selection, patients received a median of 1.7 (range, 0.82–3.1) × 10⁶ CD34⁺ cells/kg and 2.3 (range, 0.25–4.0) × 10⁵ CD3⁺ cells/kg. All patients had initial engraftment but four developed pancytopenia between days 55–130 post-BMT. In two patients, this required a second infusion of G-CSF-mobilized donor peripheral blood progenitor cells. We observed no delayed pancytopenia in a matched historical group of 24 patients receiving T cell-depleted BMT without prior G-CSF stimulation. Compared to this control group, G-CSF-stimulated marrow recipients showed a significant decline in neutrophil and monocyte counts after 8 weeks. However, outcome after BMT was otherwise comparable, with a similar incidence of acute graft-versus-host disease and transplant-related mortality. Disease-free survival was 63 vs 67% for controls matched for CD34⁺ cell dose (P = NS). These results indicate that G-CSF stimulation can increase the CD34⁺ cell content of T cell-depleted marrow but carries a risk of late graft failure.