Biology Reference
In-Depth Information
tions were found, yet only in association with other problems such as infection
or inflammation [67] while other studies showed normal concentrations [68,
69]. Blunted EPO production, however, has been seen in more recent work in
patients with cancer without complications, in contrast to patients with iron-
deficiency anemia [70-74]. Overall,a low endogenous serum EPO concentra-
tion, or at least a concentration lower than might be expected, would suggest
that rHuEPO use is warranted in cancer patients with anemia even before they
receive chemotherapy.
Chemotherapy-induced or radiotherapy-induced anemia is the most fre-
quently encountered anemia in patients with cancer [75]. Chemotherapy or
radiotherapy cause systemic changes outside the bone marrow that result in
anemia, e.g., hemolysis, blood loss, nutritional deficiency, damage to the ery-
throid populations in the bone marrow (Fig. 1), or other conditions may reduce
hemoglobin concentration [76]. The endogenous EPO concentration in such
patients can be variable depending on a host of factors including, but not lim-
ited to, tumor type and chemotherapy agent. Most patients (>50%) respond to
administered rHuEPO [77]. Whether this responsiveness results from the cor-
rection of low endogenous EPO values or a heightened response from super-
normal circulating EPO values (combining both endogenous and exogenous
material) is unclear. The observation remains that the proportion of patients
responding to rHuEPO after chemotherapy increases with increasing dose. In
the case of limited marrow damage, the problem can be overcome by rHuEPO
administration, though when marrow damage has become extensive, it is
unlikely that rHuEPO will be effective.
Other anemias
Although the most appealing indication for a recombinant protein therapeutic
may be where amounts of the endogenous prototype are limited,the discussion
earlier suggests that, in cancer at least, an endogenous EPO-deficit condition
is not the only time when using rHuEPO may be useful. In general in those
cases where endogenous serum EPO concentrations are reduced, administra-
tion of rHuEPO is most effective. Thus, the rationale for rHuEPO therapy in
iron-deficiency anemia due to limited dietary iron intake, for example, is weak.
Table 1 summarizes some anemic conditions and the rationale for rHuEPO use
in those conditions. These conditions range from an apparent EPO-deficit con-
dition documented in neonates through premature erythrocyte destruction
noted in elderly patients. Despite the different cause of these two types of ane-
mia, rHuEPO appears to be effective in both. In contrast to these anemias are
the hemoglobinopathies, where an rHuEPO-induced increase in hematocrit,
without the accompanying conversion of hemoglobin type from diseased to
fetal (e.g., with hydroxyurea therapy), would be of limited benefit. Anemia in
the various intensive care patient populations responds, in general, quite well
to rHuEPO and appears to have many features in common with ACD.
Similarly, the anemia noted in patients with AIDS, despite the multifactorial
causation, responds predictably to rHuEPO.
