The major goal of this project is to develop clinical protocols to test the effectiveness of recombinant growth factors at enhancing the rapidity and durability of hematopoietic regeneration inpatients undergoing autologous marrow transplantation (AMT). A secondary goal is to examine the reliability of culture assays for predicting clinical efficacy. A series of clinical trials is planned to test the effect of recombinant human growth factors in patients undergoing AMT. A Phase I-II dose searching study using recombinant GM-CSF in patients undergoing AMT for lymphoidneoplasia has been completed and a non-toxic, possibly efficacious regimen has been determined (250 mu g/kg/day by 2 hr infusion for 21 days). This regimen will be employed in a soon to begin Phase III trial examining the efficacy of rhGM-CSF on improving the rapidity and durability of engraftment in patients undergoing AMT for lymphoid malignancy. The trial design is randomized and double-blinded and has a planned accrual of 40 patients. An additional trial which has begun examines the effectiveness of GM-CSF in patients with late graft failure following AMT. Subsequent Phase I-II studies will use IL-3 and IL-l, alone and in combination with GM-CSF. In conjunction with these in vivo studies, a limited series of in vitro studies will examine the predictive effect of determination of the number of committed progenitor infused and their in vitro responsiveness to GM-CSF on clinical efficacy. The effect of growth factors on recovery of blood and marrow in vitro colony- forming cells from patients under clinical study will also be determined.
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