VI Autologous Bone Marrow Transplantation.pdf - Blog Science ...

Administration of rhSCF at doses of 200 mg/Kg/ day results in an approximate
doubling of marrow cellularity, as determined by sequential marrow biopsies
(9, 10
). The marrow cellularity doubles after 7 days of SCF and remains
hypercellular throughout the 28 day period of SCF treatment. At doses of 50
mg/Kg/day or less marrow cellularity is not detectably altered. The frequency
of megakaryocytes in the marrows of treated animals also increases proportionately
for the overall increase in marrow cellularity. Of interest, the frequencies of
morphologically immature cells, erythroblasts, myeloblasts and promyelocytes,
increase by 3 to 5 fold in marrows of animals after 7 days of SCF at 200 mg/Kg/
day. This is accompanied by a change in the ratio of myeloid to erythroid cells
(M:E ratio) in marrow aspirates from a pretreatment value of approximately 5:1
to almost 1:1 as well as the doubling of marrow cellularity. However, with continued
administration of rhSCF the frequency of morphologically immature cells
in marrow aspirates and the M:E ratio return to pretreatment values in the face
of persistently hypercellular marrows.
Given the in vitro findings that rhSCF enhances the proliferation of CFC we
then examined the effects of rhSCF administration on hematopoietic progenitor
cells in marrow and the circulation. In marrow, the frequencies of the different
CFC types, CFU-GM, BFU-E, CFU-MIX, and HPP-CFC (including colonies with
diameter of > 1.0 mm), remain unchanged or increase modestly, during periods
of rhSCF administration (10). Given the finding that the marrow cellularity
doubles, this strongly suggests that the total number of CFC of these different
types increases in marrow.
In blood, hematopoietic CFC can be quantified more readily. Normally,
CFC can be detected in the circulation only at very low frequencies. Administration
of rhSCF to baboons stimulates a dose dependent increase in both the relative
frequencies (per 10 5
cells) and the absolute number (per ml of blood) of
CFU-GM, BFU-E, CFU-MIX, and HPP-CFC in the circulation ( ,0
). In SCF treated
animals there is no change in numbers of circulating CFC during the first 4 days
of treatment following which there is a rapid rise on the fifth day that is maintained
throughout treatment.
Studies in mice have provided evidence that SCF administered concomitantly
with G-CSF may have synergistic effects on stimulating leukocytosis ( 11,12
).
In splenectomized mice, McNiece and colleagues found that SCF and G-CSF administered
together induce higher leukocyte counts than either G-CSF or SCF
alone ( n
). Also, the number of progenitor cells present in circulation is increased
by the combination of factors over that observed with either factor alone. These
cells are capable of engrafting lethally irradiated mice. Whether these progenitor
cell populations also include increased numbers of pluripotent stem cells capable
of serial transplantation remains to be determined.
We now have evidence that administration of low doses of rhSCF to baboons
can result in synergistic interactions with G-CSF in vivo when both factors
are administered at the same time. We studied 4 groups of baboons (3 animals
per group) that were treated for 14 days with either SCF (25 mg/Kg/day)
alone, G-CSF (100 mg/Kg/day)alone, the combination of G-CSF and SCF, or
SCF alone for 7 days followed by G-CSF alone for 7 days.
Animals administered SCF alone at a dose of 25 mg/Kg/day did not develop
a leukocytosis (Table 1 ). In 2 of these 3 animals there was no evidence for
228 SIXTH INTERNATIONAL SYMPOSIUM ON AUTOLOGOUS BONE MARROW TRANSPLANTATION