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

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

Research output: Contribution to journalArticlepeer-review

188 Scopus citations

Abstract

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 24h after infusion of the larger unmanipulated fraction. All but two units contained <2 × 107 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 68.5kg. 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 × 107/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.

Original languageEnglish (US)
Pages (from-to)771-778
Number of pages8
JournalBone Marrow Transplantation
Volume41
Issue number9
DOIs
StatePublished - May 2008
Externally publishedYes

ASJC Scopus subject areas

  • Hematology
  • Transplantation

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