Effect of Recombinant Human Granulocyte-Macrophage Colony-Stimulating Factor on Hematopoietic Reconstitution after High-Dose Chemotherapy and Autologous Bone Marrow Transplantation

Abstract

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 micrograms 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 micrograms per kilogram per day, 2575 +/- 2304 in those given 16 micrograms, and 3120 +/- 1744 in those given 32 micrograms, 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 micrograms per kilogram per day. Edema, weight gain, or myalgias occurred in all patients given 32 micrograms 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.

Recombinant human granulocyte macrophage colony stimulating factor (rhGM-CSF) given as daily short infusions – a phase I dose-toxicity study

“…His extensive pancreatic neoplasm rather than the administration of GM-CSF was felt to be the more likely cause of his embolism. A fourth patient with metastatic osteosarcoma developed severe transient dyspnoea after each infusion of GM-CSF and a similar syndrome ascribed to capillary leak with pulmonary oedema has been described in two patients receiving doses of 32 jug kg-1 following high dose chemotherapy and autologous bone marrow rescue (Brandt et al, 1988).…”

Granulocyte-macrophage colony stimulating factor (GM-CSF) after high-dose melphalan in patients with advanced colon cancer

“…Unfortunately there was one treatment-related death from renal failure which was attributed to the administration of a combination of nephrotoxic antibiotics. Acute renal failure has been reported with GM-CSF (Brandt et al, 1988) but it was reversible on discontinuing this agent and only occurred at high dose levels (32 tLg kg-' day-). It would seem unlikely that GM-CSF was the cause of renal failure in our patient as the dose used was significantly lower and there was no reversal on discontinuing the infusion.…”

Economic evaluation of cancer treatments

“…However, the procedure-associated risk of 5-15% fatal complications and the adverse effect on patients' morbidity can be serious due to a pancytopenic period of 3-4 weeks (Brandt et al, 1988). Moreover, the costs of autologous as well as allogeneic bone marrow transplantation are high, and the additional burden that these treatments place on hospital budgets raises concern (Dufoir et al, 1992;Welch and Larson, 1989).…”