HEMATOPOIETIC GROWTH-FACTORS AFTER HLA-IDENTICAL ALLOGENEIC BONE-MARROW TRANSPLANTATION IN PATIENTS TREATED WITH METHOTREXATE-CONTAINING GRAFT-VS.-HOST DISEASE PROPHYLAXIS

The use of hematopoietic growth factors (HGFs) in the allogeneic trans plant setting has sometimes been avoided for fear of stimulating leuke mic cell growth and intensifying graft-vs.-host disease (GVHD). Howeve r, neither an increase in relapse rate nor an aggravation of GVHD has been routinely described when HGFs are used after allogeneic bone marr ow transplantation (allo-BMT). Early outcomes after HLA-matched allo-B MT in 26 patients with hematologic malignancies treated with recombina nt human granulocyte colony-stimulating factor (rhG-CSF) or recombinan t human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) fr om the day of transplantation were analyzed. Results were compared to those from a series of 38 patients treated earlier with an identical a pproach, but not scheduled to receive HGFs after transplantation. All patients received a preparative regimen consisting of etoposide, cyclo phosphamide, and total-body irradiation and GVHD prophylaxis with cycl osporine and a short course of methotrexate (MTX). The analysis has sh own that the duration of neutropenia was significantly decreased in th e group of patients treated routinely with HGFs (median 17 vs. 20 days ; p < 0.001). These patients also required fewer days of intravenous a ntibiotic therapy (median 20 vs. 34 days; p < 0.001), had fewer positi ve blood and tissue cultures (median 2 vs. 12 and 13 vs. 28; p = 0.02 and p = 0.05, respectively), needed fewer packed red blood cell transf usions (median 7 vs. 11; p < 0.03), and were discharged earlier from t he hospital (median 33.5 vs. 39 days; p < 0.001). The use of HGFs was not associated with an increase in acute GVHD or early leukemic relaps e. No side effects were attributable to the simultaneous administratio n of MTX and HGF during the neutropenic period. A trend toward better 100-day actuarial survival for patients treated with rhG-CSF or rhGM-C SF did not reach statistical significance. A decrease in the number of early deaths from fungal or bacterial infections was found in the cyt okine-treated group (p = 0.05). These data suggest that the early use of rhG-CSF or rhGM-CSF after HLA-matched allo-BMT in hematologic malig nancies accelerates engraftment, reduces hospitalization time, and imp roves outcome, without increasing acute GVHD or early relapse. Because MTX-based prophylaxis regimens are associated with prolonged neutrope nia, the routine use of HGFs after transplantation may be particularly useful in regimens including MTX.