Transplantation of ex vivo expanded cord blood cells using the copper chelator tetraethylenepentamine: a phase I/II clinical trial.

Published

Journal Article

The copper chelator tetraethylenepentamine (TEPA; StemEx) was shown to attenuate the differentiation of ex vivo cultured hematopoietic cells resulting in preferential expansion of early progenitors. A phase I/II trial was performed to test the feasibility and safety of transplantation of CD133+ cord blood (CB) hematopoietic progenitors cultured in media containing stem cell factor, FLT-3 ligand, interleukin-6, thrombopoietin and TEPA. Ten patients with advanced hematological malignancies were transplanted with a CB unit originally frozen in two fractions. The smaller fraction was cultured ex vivo for 21 days and transplanted 24 h after infusion of the larger unmanipulated fraction. All but two units contained <2 x 10(7) total nucleated cells (TNCs) per kilogram pre-expansion. All donor-recipient pairs were mismatched for one or two HLA loci. Nine patients were beyond first remission; median age and weight were 21 years and 68.5 kg. The average TNCs fold expansion was 219 (range, 2-620). Mean increase of CD34+ cell count was 6 (over the CD34+ cell content in the entire unit). Despite the low TNCs per kilogram infused (median=1.8 x 10(7)/kg), nine patients engrafted. Median time to neutrophil and platelet engraftment was 30 (range, 16-46) and 48 (range, 35-105) days. There were no cases of grades 3-4 acute graft-versus-host disease (GVHD) and 100-day survival was 90%. This strategy is feasible.

Full Text

Duke Authors

Cited Authors

  • de Lima, M; McMannis, J; Gee, A; Komanduri, K; Couriel, D; Andersson, BS; Hosing, C; Khouri, I; Jones, R; Champlin, R; Karandish, S; Sadeghi, T; Peled, T; Grynspan, F; Daniely, Y; Nagler, A; Shpall, EJ

Published Date

  • May 2008

Published In

Volume / Issue

  • 41 / 9

Start / End Page

  • 771 - 778

PubMed ID

  • 18209724

Pubmed Central ID

  • 18209724

International Standard Serial Number (ISSN)

  • 0268-3369

Digital Object Identifier (DOI)

  • 10.1038/sj.bmt.1705979

Language

  • eng

Conference Location

  • England