M. Engelhardt et al., Hematopoietic recovery of ex vivo perfusion culture expanded bone marrow and unexpanded peripheral blood progenitors after myeloablative chemotherapy, BONE MAR TR, 27(3), 2001, pp. 249-259
Citations number
44
Categorie Soggetti
Hematology,"Medical Research Diagnosis & Treatment
Ex vivo culture of hematopoietic progenitor cells for autologous transplant
ation has generated world-wide interest, since it offers the prospect of us
ing a limited cell number, and may allow more efficient gene transfer and p
assive elimination of contaminating tumor cells, In this study, we expanded
bone marrow (BM) cells from 10 breast cancer patients to determine whether
small BM aliquots can durably restore hematopoiesis, and whether thrombopo
ietin (TPO) improves hematopoietic reconstitution after myeloablative chemo
therapy. We used the AastromReplicell System (ARS), performing a computer-c
ontrolled, stromal-based cell expansion process with frequent medium, cytok
ine and gas exchange, For the inoculation of 9x10(8) MNC, a median BM volum
e of 97.8 ml (range, 72.4-272) was harvested. We found a median 4.5-fold nu
cleated cell expansion, an 18-fold CFU-GM expansion, and 69% of input LTC-I
C numbers, Nucleated and Lin(-)/CD34(+) cells were infused with a median of
43.5 x 10(6)/kg (range, 34.1-71.7) and 2.8 x 10(5)/kg (range, 0.95-5.9), r
espectively, Despite tumor cell detection by immunocytochemical staining in
3/10 patients before expansion, tumor cells were not detectable in 9/10, a
nd in one patient 1 log reduced post ARS culture. Following high-dose STAMP
V chemotherapy, all patients received 12-day expanded BM cells, The median
time to engraftment was 17 days (range, 11-20) for WBC >1000/mul, and 28 d
ays (range, 21-55) for platelets >20 000/mul. A correlation between post-ex
pansion Lin(-)/CD34(+) cells and engraftment for ANC >500/mul, WBC >1000/mu
l and platelets >20 000/mul was observed. Hematopoiesis has been maintained
for a median of 15 (range, 6-24) months. Our results demonstrate that tran
splantation of ex vivo expanded small BM aliquots allows hematopoietic reco
nstitution after myeloablative chemotherapy. Ex vivo generated ARS cells ca
n reduce the risk of tumor cell reinoculation with autotransplants and may
be valuable in settings in which only small stem cell doses are available,
eg when using cord blood transplants or in non-mobilizing patients.