Blood, 1959, Vol. 14, No. 6, pp. 720-736.
© 1959 American Society of Hematology, Inc.
Homografts of Bone Marrow in Dogs After
Lethal Total-Body Radiation
E. DONNALL THOMAS 1,
CHARLES A. ASHLEY 1,
HARRY L. LOCHTE JR. 1,
ALFRED JARETZKI III 1,
OTTO D. SAHLER 1, and
JOSEPH W. FERREBEE 1
1 Mary Imogene Bassett Hospital (affiliated with Columbia University),
Cooperstown, N. Y.
Twenty-two dogs (20 males and two females) were uniformly exposed over
their entire surfaces to supralethal irradiation: 800 to 1,200 roentgens of
250 kv. x-rays measured in air at mid-body position. On the third day and
after the last exposure, these irradiated animals were given infusions of normal bone marrow. The marrow for their infusions was taken from female
litter-mates, from mothers or from unrelated dogs. Evidence for a return
of marrow function and for a successful marrow graft was evaluated on the
basis of: (1) the reappearance of formed elements: platelets, leukocytes, and
reticulocytes, in the peripheral circulation; (2) the appearance in males of
leukocytes bearing the sex-chromatin marker of the female donor; (3) prolonged survival, as compared to six irradiated control animals that were not
given marrow; and (4) cellularity of marrow spaces and histologic evidence
of marrow function at autopsy.
It was found that marrow transplants usually succeeded after 800 to 1,200
roentgens of total-body irradiation when the infused marrow was taken from
litter-mate sisters or from mothers (15 successes in 17 attempts). Marrow
transplants between unrelated animals appeared more difficult but were not
impossible. One success was obtained in five attempts, and this success was
achieved with the coincidental use of splenectomy, ACTH and a large dose
of marrow.
Dogs with successful transplants lived longer than did control animals; in
this series two to 10 times as long. When they died, they died of common
canine infectious diseases and not of marrow failure. Distemper, hepatitis
and leptospirosis, with or without superimposed bacterial respiratory disease,
were the common causes of death.
The lymph nodes and the splenic follicles of irradiated animals had, in
most instances, not regained normal histologic appearance at the time of
death from these infectious diseases. The working hypothesis is advanced
that infusions of marrow repopulate marrow spaces in the canine after irradiation but are poor sources of the type of cell needed to restore lymphoid
function and immunologic effectiveness in lymph nodes and spleen.
Submitted on August 4, 1958
Accepted on November 18, 1958