A pilot study of allogeneic bone marrow transplantation using related donors stimulated with G-CSF

Abstract

Growth factor administration to donors prior to bone marrow (BM) harvesting results in an enrichment of the graft for myeloid precursors. In animals, growth factor-primed BM has a higher repopulating ability than untreated BM. Ten patients received an HLA-identical sibling, allogeneic transplant using granulocyte colony-stimulating factor (G-CSF)-stimulated BM. Stimulation consisted of G-CSF at 10 μg/kg/day for 2 days prior to harvest. Patients were transplanted for various benign and malignant hematological conditions. The GVHD prophylaxis consisted of cyclosporine, methotrexate and/or prednisone. Compared to untreated historical control BM, stimulated BM infusions contained similar number of nucleated cells (mean ± s.d.: 3.5 ± 1.5 vs 4.0 ± 0.9 × 10⁸/kg), CD34⁺ cells (mean ± s.d.: 7.5 ± 3.0 vs 9.4 ± 6.7 × 10⁶/kg), and CD3⁺ cells (mean ± s.d.: 129 ± 30 vs 190 ± 59 × 10⁶/kg) but higher numbers of granulocyte–macrophage colony-forming units (mean ± s.d.: 20 ± 12 vs 96 ± 34 × 10⁴/kg). Patients receiving stimulated BM had prompt and stable engraftment of white cells and platelets. On average they attained an ANC of ⩾1 ×10⁹/l 9 days earlier and a platelet count of ⩾20 × 10⁹/l 6 days earlier than historical controls receiving unstimulated HLA-identical sibling BM. Hospitalization was shortened by a mean of 10 days and transfusion requirements were modest. None of the patients developed severe GVHD or disease relapse. Two patients died of severe VOD post-BMT and thus were unevaluable for platelet engraftment. A third patient died of TTP on day 76 post-BMT. Seven patients are alive and well 49–585 days post-BMT. Stimulated BM may provide a valuable alternative to allogeneic BM and PBSC transplants. Ideal stimulation regimens need to be investigated.