TY - JOUR
T1 - Effect of Recombinant Human Granulocyte-Macrophage Colony-Stimulating Factor on Hematopoietic Reconstitution after High-Dose Chemotherapy and Autologous Bone Marrow Transplantation
AU - Brandt, Stephen J.
AU - Peters, William P.
AU - Atwater, Susan K.
AU - Kurtzberg, Joanne
AU - Borowitz, Michael J.
AU - Jones, Roy B.
AU - Shpall, Elizabeth J.
AU - Bast, Robert C.
AU - Gilbert, Colleen J.
AU - Oette, Dagmar H.
PY - 1988/4/7
Y1 - 1988/4/7
N2 - Recombinant human granulocyte–macrophage colony-stimulating factor (rHuGM-CSF) has been reported to increase the leukocyte count in subhuman primates subjected to total-body irradiation and in patients with the acquired immunodeficiency syndrome. We administered this substance to 19 patients with breast cancer or melanoma treated with high-dose combination chemotherapy and autologous bone marrow support. Groups of three or four patients were treated with 2.0, 4.0, 8.0, 16.0, or 32.0 μg per kilogram of body weight per day of glycosylated rHuGM-CSF by continuous intravenous infusion for 14 days, beginning three hours after bone marrow infusion. Total leukocyte and granulocyte recovery was accelerated in these patients as compared with 24 historical controls matched for age, diagnosis, and treatment. Leukocyte counts (mean ±SD) obtained 14 days after transplantation were 1511 ±1003 per microliter in patients given 2 to 8 μg per kilogram per day, 2575+2304 in those given 16 μg, and 3120±1744 in those given 32 μg, as compared with 863±645 per microliter in the controls. No consistent effect on platelet counts was noted. Toxic effects were generally mild and not clearly dose-related in patients given 2 to 16 /ug per kilogram per day. Edema, weight gain, or myalgias occurred in all patients given 32 μg per kilogram; marked weight gain, generalized edema, pleural effusions, and hypotension developed in two patients, one of whom also had acute renal failure. Our results indicate that rHuGM-CSF can accelerate myeloid recovery after high-dose chemotherapy and autologous bone marrow transplantation, over a range of doses that can be tolerated. In this setting the ability to increase the dose is limited by the development of myalgias and fluid retention. (N Engl J Med 1988; 318: 869–76.)
AB - Recombinant human granulocyte–macrophage colony-stimulating factor (rHuGM-CSF) has been reported to increase the leukocyte count in subhuman primates subjected to total-body irradiation and in patients with the acquired immunodeficiency syndrome. We administered this substance to 19 patients with breast cancer or melanoma treated with high-dose combination chemotherapy and autologous bone marrow support. Groups of three or four patients were treated with 2.0, 4.0, 8.0, 16.0, or 32.0 μg per kilogram of body weight per day of glycosylated rHuGM-CSF by continuous intravenous infusion for 14 days, beginning three hours after bone marrow infusion. Total leukocyte and granulocyte recovery was accelerated in these patients as compared with 24 historical controls matched for age, diagnosis, and treatment. Leukocyte counts (mean ±SD) obtained 14 days after transplantation were 1511 ±1003 per microliter in patients given 2 to 8 μg per kilogram per day, 2575+2304 in those given 16 μg, and 3120±1744 in those given 32 μg, as compared with 863±645 per microliter in the controls. No consistent effect on platelet counts was noted. Toxic effects were generally mild and not clearly dose-related in patients given 2 to 16 /ug per kilogram per day. Edema, weight gain, or myalgias occurred in all patients given 32 μg per kilogram; marked weight gain, generalized edema, pleural effusions, and hypotension developed in two patients, one of whom also had acute renal failure. Our results indicate that rHuGM-CSF can accelerate myeloid recovery after high-dose chemotherapy and autologous bone marrow transplantation, over a range of doses that can be tolerated. In this setting the ability to increase the dose is limited by the development of myalgias and fluid retention. (N Engl J Med 1988; 318: 869–76.)
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U2 - 10.1056/NEJM198804073181401
DO - 10.1056/NEJM198804073181401
M3 - Article
C2 - 3281007
AN - SCOPUS:0023905962
SN - 0028-4793
VL - 318
SP - 869
EP - 876
JO - New England Journal of Medicine
JF - New England Journal of Medicine
IS - 14
ER -