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Ex vivo expansion of mafosfamide-purged PBPC products.

Abstract：

BACKGROUND:Multiple studies have demonstrated that 'purging' of autografts with 4-hydroperoxycyclophosphamide (4HC) or the related compound mafosfamide (Mf), to eradicate residual leukemia, produces the best results associated with autologous blood and marrow transplantation for AML. However, 4HC purging results in prolonged aplasia. Therefore, we evaluated the potential of ex vivo expansion of Mf-treated CD34+ cells from mobilized PBPC. METHODS:CD34+ cells were isolated from PBPC products and treated with 30 microg/mL Mf. The Mf-treated CD34+ cells were washed and cultured for 14 days in StemLine II-defined media containing recombinant human (rh) SCF, G-CSF and thrombopoietin (Tpo). RESULTS:Treatment with Mf resulted in 90% killing of progenitor cells (GM-CFC) but maintenance of SCID-repopulating cells (SRC). Ex vivo culture of the Mf-treated CD34+ cells resulted in decreased cell numbers (10-20% of the starting cell dose) during the first week. Nevertheless, in the second week of culture the total cell numbers expanded to approximately 20-fold above starting cell numbers and progenitor cells returned to approximately pre-treatment levels. DISCUSSION:These studies demonstrate the potential of ex vivo culture to expand both total cell numbers and progenitor cells following treatment of PBPC CD34+ cells with Mf. Clinical studies are currently being initiated to evaluate the engraftment potential of these purged and expanded products.

journal_name

Cytotherapy

journal_title

Cytotherapy

authors

McNiece I,Civin C,Harrington J,Kellner J,Malehorn M,Turney J,Barber J,Jones R

doi

10.1080/14653240600905353

subject

Has Abstract

pub_date

2006-01-01 00:00:00

pages

459-64

issue

5

eissn

1465-3249

issn

1477-2566

pii

N1639H4360061GX5

journal_volume

8

pub_type

临床试验,杂志文章

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