Hematopoietic recovery of ex vivo perfusion culture expanded bone marrow and unexpanded peripheral blood progenitors after myeloablative chemotherapy

Citation
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
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Hematology,"Medical Research Diagnosis & Treatment
Journal title
BONE MARROW TRANSPLANTATION
ISSN journal
0268-3369 → ACNP
Volume
27
Issue
3
Year of publication
2001
Pages
249 - 259
Database
ISI
SICI code
0268-3369(200102)27:3<249:HROEVP>2.0.ZU;2-3
Abstract
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.