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Effect of CD34+ selection and various schedules of stem cell reinfusion and
granulocyte colony-stimulating factor priming on hematopoietic recovery
after high-dose chemotherapy for breast cancer
G Somlo, I Sniecinski, T Odom-Maryon, B Nowicki, W Chow, V Hamasaki, L Leong, K Margolin, R Morgan , J Raschko, S Shibata, M Tetef, A Molina, RJ Berenson, SJ Forman and JH Doroshow
Department of Medical Oncology and Therapeutics Research, City of Hope
National Medical Center, Duarte, CA 91010-3000, USA.
We evaluated the effects of various schedules of peripheral blood stem cell
(PBSC) reinfusion, granulocyte colony-stimulating factor (G-CSF) priming,
and CD34+ enrichment on hematopoietic recovery in 88 patients with advanced
breast cancer treated with high-dose chemotherapy, consisting of cisplatin
250 mg/m2, etoposide 60 mg/kg, and cyclophosphamide 100 mg/kg. PBSC (>
or = 7.5 x 10(8) nucleated cells/kg) were collected following priming with
G-CSF and were either immediately cryopreserved (48 patients; cohorts A and
B) or were first processed for CD34+ enrichment (40 patients; cohorts C and
D). Patients in cohorts A and C received PBSC on day 0; patients in cohorts
B and D received 25% of their nucleated cells on day -2 and 75% on day 0
(split reinfusion). Patients in cohorts A, B, and C were primed with G-CSF
10 micrograms/kg, subcutaneously (SC), once a day; patients in cohort D
were primed with 5 micrograms/kg G-CSF, SC, twice daily (bid). Bid
administration of G-CSF yielded 2.3 to 4.7 x higher numbers of CD34+ cells
in the PBSC product than the same total dose given once a day (P = .002).
Reinfusion of 25% of unselected PBSC on day -2 (median, 2.26 x 10(8)/kg
nucleated cells [range, 1.7 to 3.3 x 10(8)/kg]) with the remaining cells
reinfused on day 0 resulted in earlier granulocyte recovery to > or =
500/microL when compared with reinfusion of all stem cells on day 0 (group
B, median of 8 days [range, 7 to 11] v group A, 10 days [range, 8 to 11], P
= .0003); no schedule-dependent difference was noted in reaching platelet
independence (group B, 11.5 days [range, 5 to 21]; group A, 12 days [range,
8 to 24], P = not significant). Split schedule reinfusion of
CD34(+)-selected PBSC did not accelerate granulocyte recovery. In groups D
and C, the median number of days to granulocyte recovery was 12 (range, 8
to 22) and 11.5 (range, 9 to 13); patients became platelet independent by
day 15 (range, 6 to 22) and 14 (range, 12 to 23), respectively.
CD34(+)-selected PBSC rescue decreased the incidence of postreinfusion
nausea, emesis, and oxygen desaturation in comparison to unselected PBSC
reinfusion (P < or = .005 for each). Hematopoietic recovery may be
accelerated by earlier reinfusion of approximately 2.26 x 10(8)/kg
unselected nucleated cells. Earlier recovery may be triggered by components
other than the progenitors included in the CD34+ cell population. Sustained
hematopoietic recovery can also be achieved with CD34(+)-selected PBSC
alone. Dosing of G-CSF on a bid schedule generates higher CD34+ cell yield
in the leukapheresis product. Whether even earlier "sacrificial" reinfusion
of approximately 2 x 10(8)/kg unselected nucleated cells concomitant with
the administration of high-dose chemotherapy would reduce the duration of
absolute granulocytopenia further while initiating sustained long- term
hematopoietic recovery will require further investigation.
Volume 89,
Issue 5,
pp. 1521-1528,
03/01/1997
Copyright © 1997 by The American Society of Hematology
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