A PILOT-STUDY OF ALLOGENEIC BONE-MARROW TRANSPLANTATION USING RELATEDDONORS STIMULATED WITH G-CSF

Growth factor administration to donors prior to bone marrow (BM) harve sting results in an enrichment of the graft for myeloid precursors, In animals, growth factor-primed BM has a higher repopulating ability th an untreated BM, Ten patients received an HLA-identical sibling, allog eneic transplant using granulocyte colony-stimulating factor (G-CSF)-s timulated BM. Stimulation consisted of G-CSF at 10 mu g/kg/day for 2 d ays prior to harvest, Patients were transplanted for various benign an d malignant hematological conditions, The GVHD prophylaxis consisted o f cyclosporine, methotrexate and/or prednisone, Compared to untreated historical control BM, stimulated BM infusions contained similar numbe r of nucleated cells (mean +/- s.d.: 3.5 +/- 1.5 vs 4.0 +/- 0.9 x 10(8 )/kg), CD34(+) cells (mean +/- s.d.: 7.5 +/- 3.0 vs 9.4 +/- 6.7 x 10(6 )/kg), and CD3(+) cells (mean +/- s.d.: 129 +/- 30 vs 190 +/- 59 x 10( 6)/kg) but higher numbers of granulocyte-macrophage colony-forming uni ts (mean +/- s.d.: 20 +/- 12 vs 96 +/- 34 x 10(4)/kg). Patients receiv ing stimulated BM had prompt and stable engraftment of white cells and platelets, On average they attained an ANC of greater than or equal t o 1 x 10(9)/l 9 days earlier and a platelet count of greater than or e qual to 20 x 10(9)/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 d ied of severe VOD post-BMT and thus were unevaluable for platelet engr aftment, A third patient died of TTP on day 76 post-BMT, Seven patient s are alive and well 49-585 days post-BMT, Stimulated BM may provide a valuable alternative to allogeneic BM and PBSC transplants, Ideal sti mulation regimens need to be investigated.