autologous blood and marrow transplantation - Blog Science ...

Carlo-Stella et al. 437
tissues from radiochemotherapy toxicities, and stimulates both in vitro and in vivo
hematopoiesis. 18-25
Amifostine protection on normal tissues has been demonstrated
for photoactive agents, alkylating agents, nitrogen mustard, and platinum
analogs. 26-33
Amifostine is a prodrug that is dephosphorylated by membrane-bound
alkaline phosphatase to the free thiol which is then very rapidly taken up by normal
cells, but very slowly, if at all, by tumor cells. 34,35
The mechanisms of amifostine
cytoprotection rely on its ability to neutralize the DNA-reactive moieties of
cytotoxic agents, its action as a scavenger of oxygen free radicals, and probably its
capacity to reduce apoptosis. 36-38
In a recent phase I/II clinical trial conducted in
patients with myelodysplasia syndromes, List et al. have demonstrated a
stimulation of hematopoiesis in vivo by amifostine with an important response on
myeloid progenitors. 39
We conducted a randomized clinical trial with a crossover design to evaluate the
role of amifostine in conjunction with epirubicin and G-CSF in an attempt to
improve PBPC mobilization. The effect of amifostine was investigated on the
mobilization of CD34 +
cells and primitive (LTC-IC) and committed progenitors
(CFU-Mix, BFU-E, CFU-GM).
MATERIALS AND METHODS
Patients
Ten patients ranging in age from 33 to 54 years were included in this study.
Informed consent was obtained from all patients before entry into the study. The
main clinical characteristics of the patients at the time of the study are shown in
Table 1. Prior, to the study, all but three patients had received combination
chemotherapy and two had received radiotherapy. The interval between the last
chemotherapy cycle and inclusion in the study ranged from 0.5 to 21 months.
Study design
The effect of amifostine was explored in a randomized trial with a crossover
design (Fig. 1). Patients were randomized to receive amifostine on first or second
cycle, thus each patient served as their own control. Intravenous (IV) epirubicin
(Farmorubicin, 120 mg/m 2
, day 0) followed by G-CSF (Neupogen, 5 ug/kg/d
subcutaneously, days 1-10) was administered at 3-week intervals. Amifostine
(Ethyol) was administered as a 15-minute IV infusion at the dose of 1000 mg on
day 0 (15 minutes before epirubicin) and at the dose of 500 mg on days 1^1. Before
amifostine injection, hydration was administered with normal saline (1000 mL,
IV), and ondasetron (8 mg, IV). During amifostine infusion, blood pressure was
monitored every 3-5 minutes, and serum ionized calcium levels were monitored on