Transplantation of ex vivo expanded cord blood cells using the copper chelator tetraethylenepentamine: a phase I|[sol]|II clinical trial

doi:doi:10.1038/sj.bmt.1705979

Bone Marrow Transplantation (2008) 41, 771–778; doi:10.1038/sj.bmt.1705979; published online 21 January 2008

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

M de Lima¹, J McMannis¹, A Gee², K Komanduri¹, D Couriel¹, B S Andersson¹, C Hosing¹, I Khouri¹, R Jones¹, R Champlin¹, S Karandish¹, T Sadeghi¹, T Peled³, F Grynspan³, Y Daniely³, A Nagler⁴ and E J Shpall¹

¹Department of Stem Cell Transplantation and Cell Therapy, University of Texas MD Anderson Cancer Center, Houston, TX, USA
²Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX, USA
³Gamida Cell Ltd, Jerusalem, Israel
⁴Chaim Sheba Medical Center, Tel Hashomer, Israel

Correspondence: Dr M de Lima, Department of Stem Cell Transplantation and Cell Therapy, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Unit 423, Houston, TX 77030, USA. E-mail: mdelima@mdanderson.org

Received 24 September 2007; Revised 12 November 2007; Accepted 13 November 2007; Published online 21 January 2008.

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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 24 h after infusion of the larger unmanipulated fraction. All but two units contained <2 $times$ 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 68.5 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 $times$ 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.