The mobilization with delayed G-CSF administration after standart induction chemotherapy and single standart volume apheresis can supply adequate amount of CD34(+) cells in patients with breast cancer
Fikret Arpaci, Seref
Kömürcü, Bekir Öztürk, Ahmet Özet,
Can Kinalp, Atilla Yalçin
Gata BMT Center, Etlik 06018, Ankara, Turkey.
Correspondence: F. Arpaci, Gata BMT Center, Etlik 06018, Ankara,
Turkey. E-mail: onkoloji@gata.edu.tr
We investigated if a rapid and complete engraftment could be
achieved by single apheresis without large volume leukapheresis
(LVL) using delayed addition of G-CSF after induction chemotherapy
in 27 patients with breast cancer (20 high-risk, 7 sensitive
metastatic).1 All patients received 10 microgram/kg/day
of G-CSF(Neupogen) sc or iv infusion over two hours starting on
day 14 after 3-4 cycles of FAC (fluorouracil 600 mg/m2,
adriamycin 50 mg/m2 cyclophosphamide
600mg/m2,on day 1, every three weeks) chemoterapy.
Single apheresis was performed using Cobe Spectra on days 4,5 or 6
(median 5). No growth factor was administered in posttransplant
period. WBC count at the onset of G-CSF start and at the time of
apheresis ranged between 3 and 5x109/L and 30 and
50x109/L, respectively. The median blood volume
processed per minute was found 40.20 ml/min (34.80-49.70)
resulting in a total blood volume of 11.26 L (8.97-12.84) and the
median product volume was 250 mL (250-300). The median number of
CD34 (+) cells was 5.40x106/kg (1.87-19.87). More than
2.5x106/kg CD34+ cells were obtained in 95% of
patients. Patients received a high-dose chemotherapy consisting of
cyclophosphamide (2.5 g/m2), mitoxantrone (35
mg/m2) and VP-16 (1.2 g/m2). A complete and
persistent engraftment developed in all cases. The median duration
for leucocyte (³1x109/L) and platelet
(³50x109/L) engraftments were 10 days (8-21) and 15
days (9-38), respectively. The median duration with fever was 2
days (0-6), the median posttransplant hospitalization was 11 days
(8-49), the median number of erythrocyte transfusion was 3 units
(0-6), and the median number of platelet transfusion was 2 units
(1-8). Zibera et al. reported that if G-CSF was given immediately
(on day +1 ) after 3 cycles of paclitaxel (175 mg/m2)
and epirubicin (90 mg/m2), more than
5x106/kg CD34 + cells could be obtained in 68% of
patients at a median day + 11 with single apheresis. A minimum of
two blood volumes per procedure were processed.2 In
another study, Benet and colleagues determined the effect of
delayed addition of G-CSF (8th vs 15th days, 5 mg/kg/day 4 days)
after chemotherapy on peripheral blood progenitor cells (PBPC)
mobilization in a group of 30 patients with high-risk breast
cancer undergoing standart FAC followed by stem cell
transplantation. They showed that the delayed addition of G-CSF
resulted in successful mobilization and collection of PBPC with a
significant advantage of starting G-CSF on day 8 vs day 15. In
their study, the median number of collections was three. They
didn't give any other data about their apheresis conditions
including the rate, processed blood volume, etc.3 For
autologous PBPC transplantation, an optimal mobilization time and
technique has not been clearly defined. To decrease the morbidity
and the cost, there is an inclination towards the single apheresis
collection procedures. This procedure generally requires LVL
(25-30L total blood volume) and a mobilization technique where
chemotherapy and CSFs are often combined. The most recommended
method to determine the optimal time for apheresis is daily
measurement of CD34+ cell count in circulating
blood.4,5 Three studies found the highest concentration
of CD34+ cell either 2 days after the leucocyte count reached
2x109/L6 or 1-2 days after 10x109/L (7), or
any day after reaching 5-10x109/L.8
Therefore, with the mobilization regimens where CSFs and
chemotherapy are combined, the best time for collection is the
days between 11 and 18.9 Another study reported the
days 13 to 19 for the best time of collecting.10
Although we gave a little bit higher G-CSF (10mg/kg/day, 5 days)
dosage than that of given in Benet's study (5mg/kg/day, 4 days),
our method has some useful advantages, since it provides the
opportunity of in place of three aphereses. However, apheresis
procedure itself is much more time-and money- consuming than that
amount of high dose G-CSF. Although Zibera obtained more than
5x106/ kg CD34+ cells in 68% of patients with single
apheresis, he used non-standart and more expensive chemotherapy
regimens.
In conclusion, we can say that if chemotherapy and G-CSF are given together, not only the initiation time of G-CSF after chemotherapy but also its dosage and apheresis conditions are of importance.
