Effect of BCNU combined with total body irradiation or cyclophosphamide on survival of dogs after autologous marrow grafts

Conference · Sat Sep 01 04:00:00 EDT 1979 · Int. J. Radiat. Oncol., Biol. Phys.; (United States)

OSTI ID:5275231

Paterson, A H.G.; English, D

Dogs were treated with either: (1) 750 rad total body irradiation; (2) BCNU 2 or 4 mg/kg IV 48 hours prior to 750 rad total body irradiation; or (3) BCNU 4 mg/kg IV plus cyclophosphamide 30 mg/kg IV. Results showed that of 11 dogs who received 750 rad total body irradiation and did not receive cryopreserved autologous bone marrow cells, none survived, compared to an 88% survival (31 of 35 dogs) after 750 rad total body irradiation if the dogs received stored autologous bone marrow cells. However, when the dogs were treated with BCNU 2 or 4 mg/kg prior to 750 rad total body irradiation the survival rate, despite infusion of autologous bone marrow cells, dropped to 25% (3 of 12 dogs) for BCNU 2 mg/kg, and 17% (2 of 12 dogs) for BCNU 4 mg/kg. This effect did not seem to be due to direct serum inhibition of hemopoietic cell proliferation since serum obtained at various intervals after BCNU administrations failed to inhibit CFU growth in vitro. The dogs died from hemorrhage and infection; at autopsy there was hemorrhagic pneumonitis and intestinal ulcerations with petechial hemorrhages, suggesting that the combination of BCNU and total body irradiation may have synergistic toxicity on the canine gastro-intestinal tract. When BCNU was combined with cyclophosphamide, reversal of marrow toxicity occurred in 54% (6 of 11 dogs) with stored autologous bone marrow cells compared to no survival (0 of 8 dogs) with stored autologous bone marrow cells. Thus while autologous bone marrow grafts are useful for reversal of marrow toxicity due to many therapeutic protocols, such grafts alone may not provide protection against toxicity due to the combination of high dosage BCNU and total body irradiation.

• Research Organization: University Hospital, Edmonton, Alberta
• OSTI ID: 5275231
• Conference Information: Journal Name: Int. J. Radiat. Oncol., Biol. Phys.; (United States) Journal Volume: 5:9
• Country of Publication: United States
• Language: English

Related Subjects

550603 -- Medicine-- External Radiation in Therapy-- (1980-)
560152* -- Radiation Effects on Animals-- Animals
62 RADIOLOGY AND NUCLEAR MEDICINE
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ALKYLATING AGENTS
ANIMAL CELLS
ANIMALS
ANTIMITOTIC DRUGS
BIOLOGICAL EFFECTS
BIOLOGICAL RADIATION EFFECTS
BONE MARROW CELLS
CELL PROLIFERATION
CONNECTIVE TISSUE CELLS
DIGESTIVE SYSTEM
DISEASES
DOGS
DOSES
DRUGS
ENDOXAN
EXTERNAL IRRADIATION
GASTROINTESTINAL TRACT
HEMORRHAGE
IRRADIATION
MAMMALS
NITROSO COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PATHOLOGICAL CHANGES
RADIATION DOSES
RADIATION EFFECTS
RADIOINDUCTION
RADIOSENSITIVITY EFFECTS
SIDE EFFECTS
SOMATIC CELLS
SYMPTOMS
SYNERGISM
VERTEBRATES
WHOLE-BODY IRRADIATION